Study of GSK3965193 in Healthy Participants and Participa... | NCT05330455 | Trialant
NCT05330455
Sponsor
GlaxoSmithKline
Status
Terminated
Last Update Posted
Jun 16, 2026Actual
Enrollment
74Actual
Phase
Phase 1Phase 2
Conditions
Hepatitis B
Interventions
GSK3965193
Placebo to match GSK3965193
Bepirovirsen
Countries
Canada
France
Italy
South Korea
Thailand
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT05330455
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
214760
Secondary IDs
ID
Type
Description
Link
2021-005117-13
EudraCT Number
2023-509684-24
Other Identifier
EU CTR
Brief Title
Study of GSK3965193 in Healthy Participants and Participants Living With Chronic Hepatitis B Infection
Official Title
Four-part, Randomized, Double-blind (Parts 1, 2A, 3 and 4), Multi-center, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK3965193 Monotherapy in Healthy Participants and in Participants Living With Chronic Hepatitis B Infection; and GSK3965193 in Combination With Bepirovirsen in Participants Living With Chronic Hepatitis B Infection
Acronym
Not provided
Organization
GlaxoSmithKlineINDUSTRY
Status Module
Record Verification Date
May 2026
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
The study was terminated as a strategic decision
Expanded Access Info
No
Start Date
Apr 14, 2022Actual
Primary Completion Date
May 19, 2025Actual
Completion Date
Apr 8, 2026Actual
First Submitted Date
Apr 8, 2022
First Submission Date that Met QC Criteria
Apr 8, 2022
First Posted Date
Apr 15, 2022Actual
Results Waived
Not provided
Results First Submitted Date
May 19, 2026
Results First Submitted that Met QC Criteria
May 19, 2026
Results First Posted Date
Jun 16, 2026Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
May 19, 2026
Last Update Posted Date
Jun 16, 2026Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
GlaxoSmithKlineINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
No
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
No
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This Phase 1/2a multiple part study is a first time-in-human (FTIH) study designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of single (Part 1) and repeat doses (Part 2) of GSK3965193 in healthy participants. Part 3 will evaluate the ability of GSK3965193 to lower hepatitis B virus surface antigen (HBsAg) in participants living with chronic hepatitis B infection (PLWCHB) and will be given the option to subsequently receive treatment with open label bepirovirsen. Part 4 will evaluate the safety and tolerability of combination therapy with GSK3965193 and bepirovirsen and the potential to effect sustained virologic response in PLWCHB.
Detailed Description
Not provided
Conditions Module
Conditions
Hepatitis B
Keywords
Bepirovirsen
Chronic hepatitis B
First-time-in-human
GSK3965193
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
74Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Part 1: Cohort 1 - Placebo/GSK3965193 Dose 2/Dose 3/Dose 4
Experimental
Healthy participants received a single dose of placebo oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 2 oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 3 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 4 oral solution on Day 1 in Treatment Period 4. Dose 4 of GSK3965193 was higher than Dose 3 and Dose 3 was higher than Dose 2.
Drug: GSK3965193
Drug: Placebo to match GSK3965193
Part 1: Cohort 1 - GSK3965193 Dose 1/Placebo/Dose 3/Dose 4
Experimental
Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in Treatment Period 1; followed by a single dose of placebo oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 3 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 4 oral solution on Day 1 in Treatment Period 4. Dose 4 of GSK3965193 was higher than Dose 3 and Dose 3 was higher than Dose 1.
Drug: GSK3965193
Drug: Placebo to match GSK3965193
Part 1: Cohort 1 - GSK3965193 Dose 1/Dose 2/Placebo/Dose 4
Experimental
Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 2 oral solution on Day 1 in Treatment Period 2; followed by a single dose of placebo oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 4 oral solution on Day 1 in Treatment Period 4. Dose 4 of GSK3965193 was higher than Dose 2 and Dose 2 was higher than Dose 1.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
GSK3965193
Drug
GSK3965193 was administered
Part 1: Cohort 1 - GSK3965193 Dose 1/Dose 2/Dose 3/Placebo
Part 1: Cohort 1 - GSK3965193 Dose 1/Dose 2/Placebo/Dose 4
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Treatment Emergent Adverse Events (STEAEs), and Treatment Withdrawals Due to TEAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE was considered treatment emergent if the AE onset date was on or after study intervention start date (i.e., Day 1) till Day 5 after study intervention administration. Any AE which started post Day 5 of study intervention administration was not considered as TEAE.
From the start of study intervention (Day 1) up to 12 weeks
Part 2A: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals Due to TEAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE was considered treatment emergent if the AE onset date was on or after study intervention start date.
From the start of study intervention (Day 1) up to 6 weeks
Part 2B: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals Due to TEAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE was considered treatment emergent if the AE onset date was on or after study intervention start date (i.e., Day 1) till Day 5 after study intervention administration. Any AE which started post Day 5 of study intervention administration was not considered as TEAE.
Secondary Outcomes
Measure
Description
Time Frame
Part 2B: AUC(0-inf) of GSK3965193 Following Single Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 48 h, and 72 h post-dose
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Parts 1 and 2: Participants between 18 and 55 years of age inclusive, at the time of signing the informed consent.
Parts 3 and 4: Participants between 18 and 65 years of age inclusive, at the time of signing the informed consent.
Body weight >=50 kilograms (kg) and body mass index within the range 18-32 kilograms per square meter (kg/m^2) (inclusive).
Male or female participant: a. Parts 1 and 2: woman of nonchildbearing potential only. b. Parts 3 and 4: woman of nonchildbearing potential or woman of child-bearing potential who is not pregnant or breastfeeding and is using a contraceptive method that is highly effective.
Capable of giving signed informed consent.
Additional Inclusion Criteria for PLWCHB (Parts 3 and 4).
Participants who have documented chronic hepatitis B virus (HBV) infection >=6 months prior to screening.
Participants currently receiving stable NA therapy (e.g., tenofovir disoproxil, tenofovir alafenamide, entecavir).
Plasma or serum HBsAg concentration >100 IU/mL.
Plasma or serum HBV deoxyribonucleic acid (DNA) concentration <90 IU/mL.
Hepatitis B virus e-antigen (HBeAg) positive or negative.
Alanine aminotransferase (ALT) <=2 times the upper limit of normal (ULN)
Exclusion Criteria:
Exclusion Criteria for Healthy Participants:
Positive Hepatitis A virus antibody (HAV Ab immunoglobulin M [IgM]), or positive for HBV, hepatitis C virus (HCV) or human immunodeficiency virus (HIV) at screening
A current diagnosis of migraine headache
ALT >1 times ULN.
Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent [%])
Signs and symptoms suggestive of Coronavirus Disease 2019 (COVID-19)
Participants with known COVID-19 positive contacts in the past 14 days.
For participants in Part 2A: i. Personal history or family history of peripheral neuropathy. ii. A score ≥4 on the Toronto clinical scoring system for polyneuropathy
Current or previous use of tobacco- or nicotine-containing products (for example (e.g.) cigarettes, nicotine patches or electronic devices) within 6 months before screening and/or have a smoking pack history of >5 pack years
Exclusion Criteria for PLWCHB:
Clinically significant abnormalities affecting physical or mental health in medical history or on physical examination, aside from chronic HBV infection.
Co-infection with or past history of HCV, HIV or Hepatitis D virus (HDV).
History of or suspected liver cirrhosis and/or evidence of cirrhosis.
Diagnosed or suspected hepatocellular carcinoma.
History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection (e.g., skin cancer).
History of vasculitis or presence of symptoms and signs of potential vasculitis [e.g., vasculitic rash, skin ulceration, repeated blood detected in urine without identified cause] or history/presence of other diseases Exclusion Criteria for Healthy Participants:
Positive Hepatitis A virus antibody (HAV Ab immunoglobulin M [IgM]), or positive for HBV, hepatitis C virus (HCV) or human immunodeficiency virus (HIV) at screening.
A current diagnosis of migraine headache
ALT >1 times ULN.
Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent [%]).
Signs and symptoms suggestive of Coronavirus Disease 2019 (COVID-19).
Participants with known COVID-19 positive contacts in the past 14 days.
For participants in Part 2A: i. Personal history or family history of peripheral neuropathy. ii. A score ≥4 on the Toronto clinical scoring system for polyneuropathy.
Current or previous use of tobacco- or nicotine-containing products (for example (e.g.) cigarettes, nicotine patches or electronic devices) within 6 months before screening and/or have a smoking pack history of >5 pack years
Exclusion Criteria for PLWCHB:
Clinically significant abnormalities affecting physical or mental health in medical history or on physical examination, aside from chronic HBV infection.
Co-infection with or past history of HCV, HIV or Hepatitis D virus (HDV).
History of or suspected liver cirrhosis and/or evidence of cirrhosis.
Diagnosed or suspected hepatocellular carcinoma.
History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection (e.g., skin cancer).
History of vasculitis or presence of symptoms and signs of potential vasculitis [e.g., vasculitic rash, skin ulceration, repeated blood detected in urine without identified cause] or history/presence of other diseases that may be associated with vasculitis condition (e.g., systemic lupus erythematosus, rheumatoid arthritis, relapsing polychondritis, mononeuritis multiplex).
History of extrahepatic disorders possibly related to HBV immune conditions (e.g., nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa, cryoglobulinaemia, uncontrolled hypertension).
History of alcohol or drug abuse/dependence: a. Current alcohol use as judged by investigator to potentially interfere with participant compliance. b. History of or current drug abuse/dependence as judged by the investigator to potentially interfere with participant compliance.
History or other evidence of bleeding from esophageal varices.
Documented history or other evidence of metabolic liver disease within 1 year of randomization.
Personal history or family history of peripheral neuropathy.
A score >4 on the Toronto clinical scoring system for polyneuropathy.
History of having received or currently receiving any systemic anti-neoplastic (including radiation) or immune-modulatory treatment (including systemic oral corticosteroids, interferon or pegylated interferon) within the 3 months prior to randomization or the expectation that such treatment will be needed at any time during the study.
Abnormal and clinically significant 12-lead ECG finding.
Currently taking, or taken within 3 months prior to randomization, any immunosuppressing drugs (e.g., prednisone), other than a short course of therapy (≤2 weeks) or topical/inhaled steroid use.
Prior treatment with any oligonucleotide or small interfering RNA (siRNA) within 12 months prior to the first dosing day.
Positive test for COVID-19 infection.
Accepts Healthy Volunteers
Yes
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
65 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
GSK Clinical Trials
GlaxoSmithKline
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
GSK Investigational Site
Calgary
Alberta
T2N 4Z6
Canada
GSK Investigational Site
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
Plan to Share IPD
Yes
Description
IPD for this study will be made available via the Clinical Study Data Request site.
Types
Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame
IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
The study enrolled 74 participants (20 in Part 1, 23 in Part 2A, 13 in Part 2B, and 18 in Part 3). Part 2B was planned to have 3 treatment periods (TPs). However, TP3 was not conducted following safety and tolerability findings in TP2. The study was terminated after completion of Part 3 as a strategic decision. Hence, no participants were enrolled in Part 4. Dose 1 (D1) was the lowest dose. Doses in ascending order are as follows: D1, D2, D3, D4, D9, D5, D10, D6, D7, and D8.
Recruitment Details
The study was planned to be conducted in 4 parts. Part 1, a crossover study, consisted of 2 cohorts (Cohorts 1 and 2). Part 2 consisted of 2 sub-parts: Part 2A was a parallel group study comprised of 3 cohorts (Cohorts 3, 4, and 5); and Part 2B was a crossover study comprised of 1 cohort (Cohort 6). Part 3 was a parallel group study comprised of 1 cohort (Cohort 7). Part 4 was planned to be a parallel group study comprised of 1 cohort (Cohort 8).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Part 1: Cohort 1 - Placebo/GSK3965193 Dose 2/Dose 3/Dose 4
Healthy participants received a single dose of placebo oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 2 oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 3 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 4 oral solution on Day 1 in Treatment Period 4. Dose 4 of GSK3965193 was higher than Dose 3 and Dose 3 was higher than Dose 2.
Periods
Title
Milestones
Reasons Not Completed
Part 1, Cohort 1: Treatment Period 1
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
0
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Mar 17, 2025
May 19, 2026
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
No data available
No data is available for this block.
Randomized
Intervention Model
Crossover Assignment
Intervention Model Description
Parts 1 and Part 2B are crossover and Part 2A, Part 3 and Part 4 are parallel group
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Triple
Masking Description
This is a double-blind study
Who Masked
ParticipantCare ProviderInvestigator
Drug: GSK3965193
Drug: Placebo to match GSK3965193
Part 1: Cohort 1 - GSK3965193 Dose 1/Dose 2/Dose 3/Placebo
Experimental
Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 2 oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 3 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of placebo oral solution on Day 1 in Treatment Period 4. Dose 3 of GSK3965193 was higher than Dose 2 and Dose 2 was higher than Dose 1.
Drug: GSK3965193
Drug: Placebo to match GSK3965193
Part 1: Cohort 2 - Placebo/GSK3965193 Dose 6/Dose 7/Dose 8
Experimental
Healthy participants received a single dose of placebo oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 6 oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 7 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 8 oral solution on Day 1 in Treatment Period 4. Dose 8 of GSK3965193 was higher than Dose 7 and Dose 7 was higher than Dose 6.
Drug: GSK3965193
Drug: Placebo to match GSK3965193
Part 1: Cohort 2 - GSK3965193 Dose 5/Placebo/Dose 7/Dose 8
Experimental
Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in Treatment Period 1; followed by a single dose of placebo oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 7 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 8 oral solution on Day 1 in Treatment Period 4. Dose 8 of GSK3965193 was higher than Dose 7 and Dose 7 was higher than Dose 5.
Drug: GSK3965193
Drug: Placebo to match GSK3965193
Part 1: Cohort 2 - GSK3965193 Dose 5/Dose 6/Placebo/Dose 8
Experimental
Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 6 oral solution on Day 1 in Treatment Period 2; followed by a single dose of placebo oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 8 oral solution on Day 1 in Treatment Period 4. Dose 8 of GSK3965193 was higher than Dose 6 and Dose 6 was higher than Dose 5.
Drug: GSK3965193
Drug: Placebo to match GSK3965193
Part 1: Cohort 2 - GSK3965193 Dose 5/Dose 6/Dose 7/Placebo
Experimental
Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 6 oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 7 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of placebo oral solution on Day 1 in Treatment Period 4. Dose 7 of GSK3965193 was higher than Dose 6 and Dose 6 was higher than Dose 5.
Drug: GSK3965193
Drug: Placebo to match GSK3965193
Part 2A: Placebo
Placebo Comparator
Healthy participants received repeat doses of placebo oral solution twice daily (BID) for 14 days.
Drug: Placebo to match GSK3965193
Part 2A: Cohort 5 - GSK3965193 Dose 9 BID
Experimental
Healthy participants received repeat doses of GSK3965193 Dose 9 oral solution BID for 14 days. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
Drug: GSK3965193
Part 2A: Cohort 3 - GSK3965193 Dose 5 BID
Experimental
Healthy participants received repeat doses of GSK3965193 Dose 5 oral solution BID for 14 days. Dose 5 of GSK3965193 was higher than Dose 9 but lower than Dose 10.
Drug: GSK3965193
Part 2A: Cohort 4 - GSK3965193 Dose 6 BID
Experimental
Healthy participants received repeat doses of GSK3965193 Dose 6 oral solution BID for 14 days. Dose 6 of GSK3965193 was higher than Dose 10 but lower than Dose 7.
Drug: GSK3965193
Part 2B: Cohort 6 - GSK3965193 Dose 10 Fasted/Fed
Experimental
Healthy participants received GSK3965193 Dose 10 oral tablets under fasted condition in Treatment Period 1, followed by GSK3965193 Dose 10 oral tablets under fed condition in Treatment Period 2. Dose 10 of GSK3965193 was higher than Dose 5 but lower than Dose 6.
Drug: GSK3965193
Part 2B: Cohort 6 - GSK3965193 Dose 10 Fed/Fasted
Experimental
Healthy participants received GSK3965193 Dose 10 oral tablets under fed condition in Treatment Period 1, followed by GSK3965193 Dose 10 oral tablets under fasted condition in Treatment Period 2. Dose 10 of GSK3965193 was higher than Dose 5 but lower than Dose 6.
Drug: GSK3965193
Part 3: Cohort 7 - Placebo
Placebo Comparator
Participants living with chronic hepatitis B infection (PLWCHB) on stable nucleos(t)ide analog (NA) therapy received repeat doses of placebo oral tablets for 28 days. Participants who completed placebo monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen subcutaneous (SC) injection from Day 43.
Drug: Placebo to match GSK3965193
Drug: Bepirovirsen
Part 3: Cohort 7 - GSK3965193 Dose 9
Experimental
PLWCHB on stable NA therapy received repeat doses of GSK3965193 Dose 9 oral tablets for 28 days. Participants who completed GSK3965193 monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen SC injection from Day 43. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
Drug: GSK3965193
Drug: Bepirovirsen
Part 4: Cohort 8 - Placebo + Bepirovirsen
Experimental
PLWCHB on stable NA therapy were planned to receive placebo oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
Drug: Placebo to match GSK3965193
Drug: Bepirovirsen
Part 4: Cohort 8 - GSK3965193 + Bepirovirsen
Experimental
PLWCHB on stable NA therapy were planned to receive GSK3965193 oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
Drug: GSK3965193
Drug: Bepirovirsen
Part 1: Cohort 1 - GSK3965193 Dose 1/Placebo/Dose 3/Dose 4
Part 1: Cohort 1 - Placebo/GSK3965193 Dose 2/Dose 3/Dose 4
Part 1: Cohort 2 - GSK3965193 Dose 5/Dose 6/Dose 7/Placebo
Part 1: Cohort 2 - GSK3965193 Dose 5/Dose 6/Placebo/Dose 8
Part 1: Cohort 2 - GSK3965193 Dose 5/Placebo/Dose 7/Dose 8
Part 1: Cohort 2 - Placebo/GSK3965193 Dose 6/Dose 7/Dose 8
Part 2A: Cohort 3 - GSK3965193 Dose 5 BID
Part 2A: Cohort 4 - GSK3965193 Dose 6 BID
Part 2A: Cohort 5 - GSK3965193 Dose 9 BID
Part 2B: Cohort 6 - GSK3965193 Dose 10 Fasted/Fed
Part 2B: Cohort 6 - GSK3965193 Dose 10 Fed/Fasted
Part 3: Cohort 7 - GSK3965193 Dose 9
Part 4: Cohort 8 - GSK3965193 + Bepirovirsen
Placebo to match GSK3965193
Drug
Placebo to match GSK3965193 was administered
Part 1: Cohort 1 - GSK3965193 Dose 1/Dose 2/Dose 3/Placebo
Part 1: Cohort 1 - GSK3965193 Dose 1/Dose 2/Placebo/Dose 4
Part 1: Cohort 1 - GSK3965193 Dose 1/Placebo/Dose 3/Dose 4
Part 1: Cohort 1 - Placebo/GSK3965193 Dose 2/Dose 3/Dose 4
Part 1: Cohort 2 - GSK3965193 Dose 5/Dose 6/Dose 7/Placebo
Part 1: Cohort 2 - GSK3965193 Dose 5/Dose 6/Placebo/Dose 8
Part 1: Cohort 2 - GSK3965193 Dose 5/Placebo/Dose 7/Dose 8
Part 1: Cohort 2 - Placebo/GSK3965193 Dose 6/Dose 7/Dose 8
Part 2A: Placebo
Part 3: Cohort 7 - Placebo
Part 4: Cohort 8 - Placebo + Bepirovirsen
Bepirovirsen
Drug
Bepirovirsen was administered
Part 3: Cohort 7 - GSK3965193 Dose 9
Part 3: Cohort 7 - Placebo
Part 4: Cohort 8 - GSK3965193 + Bepirovirsen
Part 4: Cohort 8 - Placebo + Bepirovirsen
From the start of study intervention (Day 1) up to 9 weeks
Part 3: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals Due to TEAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE was considered treatment emergent if the AE onset or worsen date was on or after study intervention start date. Data for the placebo or GSK3965193 monotherapy phase were presented.
From the start of study intervention (Day 1) up to 6 weeks
Part 4: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals Due to TEAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE would be considered treatment emergent if the AE onset or worsen date was on or after study intervention start date.
From the start of study intervention (Day 1) up to 48 weeks
Part 1: Number of Participants With Clinically Significant Hematology and Clinical Chemistry Parameters
Blood samples were collected to analyze hematology and clinical chemistry parameters: platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, RBC indices (mean corpuscular volume [MCV] and mean corpuscular hemoglobin [MCH]), white blood cell (WBC) count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), blood urea nitrogen (BUN), creatinine, glucose (non-fasting), potassium, sodium, calcium, aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT), alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Clinical significance of laboratory parameters was determined by the investigator.
At Day 2
Part 2A: Number of Participants With Clinically Significant Hematology, Clinical Chemistry, and Urinalysis Parameters
Blood samples were collected to analyze hematology and clinical chemistry parameters: platelet count, RBC count, hemoglobin, hematocrit, RBC indices (MCV and MCH), WBC count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), BUN, creatinine, glucose (non-fasting), potassium, sodium, calcium, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Urine samples were analyzed using automated urinalysis or urine dipstick. Microscopic examination was performed if abnormal blood or protein was present in the urine sample. Clinical significance of laboratory parameters was determined by the investigator.
Up to 21 days
Part 2B: Number of Participants With Clinically Significant Hematology, Clinical Chemistry, and Urinalysis Parameters
Blood samples were collected to analyze hematology and clinical chemistry parameters: platelet count, RBC count, hemoglobin, hematocrit, RBC indices (MCV and MCH), WBC count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), BUN, creatinine, glucose (non-fasting), potassium, sodium, calcium, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Urine samples were analyzed using automated urinalysis or urine dipstick. Microscopic examination was performed if abnormal blood or protein was present in the urine sample. Clinical significance of laboratory parameters was determined by the investigator.
Up to 9 weeks
Part 3: Number of Participants With Clinically Significant Hematology and Clinical Chemistry Parameters
Blood samples were collected to analyze hematology and clinical chemistry parameters: platelet count, RBC count, hemoglobin, hematocrit, RBC indices (MCV and MCH), WBC count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), BUN, creatinine, glucose (non-fasting), potassium, sodium, calcium, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Clinical significance of laboratory parameters was determined by the investigator. Data for the placebo or GSK3965193 monotherapy phase were presented.
Up to 35 days
Part 3: Number of Participants With Clinically Significant Urinalysis Parameters
Urine samples were analyzed using automated urinalysis or urine dipstick. Microscopic examination was performed if abnormal blood or protein was present in the urine sample. Clinical significance of laboratory parameters was determined by the investigator. Data for the placebo or GSK3965193 monotherapy phase were presented.
Up to 28 days
Part 4: Number of Participants With Clinically Significant Hematology, Clinical Chemistry, and Urinalysis Parameters
Blood samples were planned to be collected to analyze hematology and clinical chemistry parameters: platelet count, RBC count, hemoglobin, hematocrit, RBC indices (MCV and MCH), WBC count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), BUN, creatinine, glucose (non-fasting), potassium, sodium, calcium, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Urine samples were planned to be analyzed using automated urinalysis or urine dipstick. Microscopic examination was planned to be performed if abnormal blood or protein was present in the urine sample. Clinical significance of laboratory parameters would be determined by the investigator.
Up to 48 weeks
Part 1: Number of Participants With Clinically Significant Vital Sign Findings
Vital signs included systolic blood pressure (SBP) and diastolic blood pressure (DBP), pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings was determined by the investigator.
Up to 12 weeks
Part 2A: Number of Participants With Clinically Significant Vital Sign Findings
Vital signs included SBP and DBP, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings was determined by the investigator.
Up to 21 days
Part 2B: Number of Participants With Clinically Significant Vital Sign Findings
Vital signs included SBP and DBP, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings was determined by the investigator.
Up to 9 weeks
Part 3: Number of Participants With Clinically Significant Vital Sign Findings
Vital signs included temperature, SBP and DBP, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings was determined by the investigator. Data for the placebo or GSK3965193 monotherapy phase were presented.
Up to 35 days
Part 4: Number of Participants With Clinically Significant Vital Signs Findings
Vital signs were planned to include temperature, SBP and DBP, pulse and respiratory rate and were planned to be measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings would be determined by the investigator.
Up to 48 weeks
Part 1: Number of Participants With Clinically Significant Electrocardiogram [ECG] Findings
A 12-lead ECG was recorded with the participant in a semi-supine position after 5 minutes of rest using an ECG machine. The parameters collected were PR, QRS, QT, and corrected QT (QTc) intervals. Clinical significance of ECG parameters was determined by the investigator.
Up to 12 weeks
Part 2A: Number of Participants With Clinically Significant ECG Findings
A 12-lead ECG was recorded with the participant in a semi-supine position after 5 minutes of rest using an ECG machine. The parameters collected were PR, QRS, QT, and QTc intervals. Clinical significance of ECG parameters was determined by the investigator.
Up to 21 days
Part 3: Number of Participants With Clinically Significant ECG Findings
A 12-lead ECG was recorded with the participant in a semi-supine position after 5 minutes of rest using an ECG machine. The parameters collected were PR, QRS, QT, and QTc intervals. Clinical significance of ECG parameters was determined by the investigator. Data for the placebo or GSK3965193 monotherapy phase were presented.
Up to 35 days
Part 4: Number of Participants With Clinically Significant ECG Findings
A 12-lead ECG was planned to be recorded with the participant in a semi-supine position after 5 minutes of rest using an ECG machine. The parameters planned to be collected were PR, QRS, QT, and QTc intervals. Clinical significance of ECG findings would be determined by the investigator.
Up to 25 weeks
Part 2A: Number of Participants With Changes in Sensory Nerve Conduction at Day 7
Sensory nerve conduction testing was performed to detect neuropathy in participants. Nerve conduction velocity (NCV) and nerve conduction amplitude were determined. Sensory nerve conduction studies at Baseline were collected twice, one at the time of screen and one prior to dosing. Mean (arithmetic mean) of two measurements were considered as Baseline. Number of participants with 25 percent (%) decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 7 was reported.
Baseline and Day 7
Part 2A: Number of Participants With Changes in Sensory Nerve Conduction at Day 14
Sensory nerve conduction testing was performed to detect neuropathy in participants. NCV and nerve conduction amplitude were determined. Sensory nerve conduction studies at Baseline were collected twice, one at the time of screen and one prior to dosing. Mean (arithmetic mean) of two measurements were considered as Baseline. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 14 was reported.
Baseline and Day 14
Part 2A: Number of Participants With Changes in Sensory Nerve Conduction at Day 42
Sensory nerve conduction testing was performed to detect neuropathy in participants. NCV and nerve conduction amplitude were determined. Sensory nerve conduction studies at Baseline were collected twice, one at the time of screen and one prior to dosing. Mean (arithmetic mean) of two measurements were considered as Baseline. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 42 was reported.
Baseline and Day 42
Part 3: Number of Participants With Changes in Sensory Nerve Conduction at Day 15
Sensory nerve conduction testing was performed to detect neuropathy in participants. NCV and nerve conduction amplitude were determined. The best measurement out of Screening and Day -1 was considered as Baseline, best being the higher measurement. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 15 for the placebo or GSK3965193 monotherapy phase was reported.
Baseline and Day 15
Part 3: Number of Participants With Changes in Sensory Nerve Conduction at Day 29
Sensory nerve conduction testing was performed to detect neuropathy in participants. NCV and nerve conduction amplitude were determined. The best measurement out of Screening and Day -1 was considered as Baseline, best being the higher measurement. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 29 for the placebo or GSK3965193 monotherapy phase was reported.
Baseline and Day 29
Part 4: Number of Participants With Changes in Sensory Nerve Conduction
Sensory nerve conduction testing was planned to be performed to detect neuropathy in participants. NCV and nerve conduction amplitude were planned to be determined. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from baseline was planned to be reported.
Baseline up to 29 days
Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3965193 Following Single Dose Administration
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours (h) post-dose
Part 2A: AUC Over the Dosing Interval Tau (AUC[0-tau]) of GSK3965193 Following Repeat Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods. As the dosing interval Tau was 12 hours, AUC(0-tau) is the same as AUC from time zero to 12 hours after dosing (AUC[0-12]).
Pre-dose and 15 minutes (min), 30 min, 1 h, 2 h, 3 h, 4, h, 8 h, and 12 h post-first dose on Day 1; pre-dose and 15 min, 30 min, 1 h, 2h, 4 h, 8 h, and 12 h post-first dose on Day 14
Part 1: Maximum Observed Concentration (Cmax) of GSK3965193 Following Single Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post-dose
Part 2A: Cmax of GSK3965193 Following Repeat Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4, h, 8 h, and 12 h post-first dose on Day 1; pre-morning dose on Days 2 through 6 and Days 12 through 13; pre-dose and 15 min, 30 min, 1 h, 2h, 4 h, 8 h, 12 h, 24 h, 48 h, and 72 h post-first dose on Day 14
Part 1: Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK3965193 Following Single Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post-dose
Part 2A: Tmax of GSK3965193 Following Repeat Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4, h, 8 h, and 12 h post-first dose on Day 1; pre-morning dose on Days 2 through 6 and Days 12 through 13; pre-dose and 15 min, 30 min, 1 h, 2h, 4 h, 8 h, 12 h, 24 h, 48 h, and 72 h post-first dose on Day 14
Part 1: Apparent Terminal Half-life (T1/2) of GSK3965193 Following Single Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post-dose
Part 2A: T1/2 of GSK3965193 Following Repeat Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4, h, 8 h, and 12 h post-first dose on Day 1; pre-morning dose on Days 2 through 6 and Days 12 through 13; pre-dose and 15 min, 30 min, 1 h, 2h, 4 h, 8 h, 12 h, 24 h, 48 h, and 72 h post-first dose on Day 14
Part 3: Maximum Reduction of Serum HBsAg Levels From Baseline
Blood samples were collected from participants to assess HBsAg levels for the placebo or GSK3965193 monotherapy phase. Baseline was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Posterior mean and associated 95 percent (%) credible interval were derived for maximum reduction of serum HBsAg levels from Baseline using Bayesian mixed model repeated measures. The data presented are mean referring to posterior mean, with 95% confidence interval referring to 95% credible interval.
From Baseline (Pre-dose on Day 1) up to 6 weeks
Part 4: Number of Participants Achieving Complete Response
Blood samples were planned to be collected to assess HBsAg and hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Complete response is defined HBsAg and HBV DNA below lower limit of quantification (LLOQ) for 6 consecutive months after the planned end of treatment.
Up to 48 weeks
Part 2B: Cmax of GSK3965193 Following Single Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 48 h, and 72 h post-dose
Part 3: AUC(0-tau) of GSK3965193 Following Repeat Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 1; pre-dose on Day 4, Day 8, Day 11, Day 15, Day 22; pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 28
Part 3: Cmax of GSK3965193 Following Repeat Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 1; pre-dose on Day 4, Day 8, Day 11, Day 15, Day 22; pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 28
Part 3: Tmax of GSK3965193 Following Repeat Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 1; pre-dose on Day 4, Day 8, Day 11, Day 15, Day 22; pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 28
Part 3: T1/2 of GSK3965193 Following Repeat Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 1; pre-dose on Day 4, Day 8, Day 11, Day 15, Day 22; pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 28
Part 3: Number of Participants With Greater Than or Equal to [≥] 0.5 Times Log International Units Per Milliliters [IU/mL] Reduction From Baseline in Serum HBsAg Levels
Blood samples were collected from participants at indicated time points to assess HBsAg levels.
From Baseline (Day 1) up to 42 days
Part 3: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals Due to TEAEs Among Participants Opting for Optional Bepirovirsen Treatment
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator.
From the start of study intervention up to 54 weeks
Part 3: Number of Participants With Clinically Significant Hematology, Clinical Chemistry, and Urinalysis Parameters Among Participants Opting for Optional Bepirovirsen Treatment
Blood samples were planned to be collected to analyze clinical chemistry and hematology parameters: hemoglobin, leukocytes, lymphocytes/leukocytes, neutrophils/leukocytes, platelets, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cells, reticulocytes, ALT, albumin, alkaline phosphatase, AST, bilirubin, calcium corrected for albumin, creatinine, glucose, potassium, and sodium. Urine samples were planned to be analyzed using automated urinalysis or urine dipstick. Microscopic examination was performed if abnormal blood or protein was present in the urine sample. Number of participants with clinically significant clinical chemistry, hematology, and urinalysis parameters were reported. Clinical significance was determined by the investigator.
From Week 7 up to 54 weeks
Part 3: Number of Participants With Clinically Significant Vital Signs Among Participants Opting for Optional Bepirovirsen Treatment
Vital signs were planned to include temperature and were planned to be measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of vital signs was determined by the investigator.
From Week 7 up to 54 weeks
Part 4: Number of Participants With HBsAg Loss
Blood samples were collected from participants at indicated time points to assess HBsAg levels. HBsAg loss is defined by two consecutive measurements of HBsAg below the LLOQ any time during the study (on-treatment and post-treatment).
Up to 48 weeks
Ottawa
Ontario
K1H 8L6
Canada
GSK Investigational Site
Grenoble
38043
France
GSK Investigational Site
Nantes
44000
France
GSK Investigational Site
Rennes
35033
France
GSK Investigational Site
Milan
20122
Italy
GSK Investigational Site
Monza MB
20900
Italy
GSK Investigational Site
Daegu
41944
South Korea
GSK Investigational Site
Pusan
49241
South Korea
GSK Investigational Site
Seoul
05505
South Korea
GSK Investigational Site
Bangkok
10330
Thailand
GSK Investigational Site
Cambridge
CB2 2GG
United Kingdom
GSK Investigational Site
London
SW17 0QT
United Kingdom
GSK Investigational Site
London
W2 1NY
United Kingdom
FG001
Part 1: Cohort 1 - GSK3965193 Dose 1/Placebo/Dose 3/Dose 4
Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in Treatment Period 1; followed by a single dose of placebo oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 3 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 4 oral solution on Day 1 in Treatment Period 4. Dose 4 of GSK3965193 was higher than Dose 3 and Dose 3 was higher than Dose 1.
FG002
Part 1: Cohort 1 - GSK3965193 Dose 1/Dose 2/Placebo/Dose 4
Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 2 oral solution on Day 1 in Treatment Period 2; followed by a single dose of placebo oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 4 oral solution on Day 1 in Treatment Period 4. Dose 4 of GSK3965193 was higher than Dose 2 and Dose 2 was higher than Dose 1.
FG003
Part 1: Cohort 1 - GSK3965193 Dose 1/Dose 2/Dose 3/Placebo
Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 2 oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 3 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of placebo oral solution on Day 1 in Treatment Period 4. Dose 3 of GSK3965193 was higher than Dose 2 and Dose 2 was higher than Dose 1.
FG004
Part 1: Cohort 2 - Placebo/GSK3965193 Dose 6/Dose 7/Dose 8
Healthy participants received a single dose of placebo oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 6 oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 7 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 8 oral solution on Day 1 in Treatment Period 4. Dose 8 of GSK3965193 was higher than Dose 7 and Dose 7 was higher than Dose 6.
FG005
Part 1: Cohort 2 - GSK3965193 Dose 5/Placebo/Dose 7/Dose 8
Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in Treatment Period 1; followed by a single dose of placebo oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 7 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 8 oral solution on Day 1 in Treatment Period 4. Dose 8 of GSK3965193 was higher than Dose 7 and Dose 7 was higher than Dose 5.
FG006
Part 1: Cohort 2 - GSK3965193 Dose 5/Dose 6/Placebo/Dose 8
Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 6 oral solution on Day 1 in Treatment Period 2; followed by a single dose of placebo oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 8 oral solution on Day 1 in Treatment Period 4. Dose 8 of GSK3965193 was higher than Dose 6 and Dose 6 was higher than Dose 5.
FG007
Part 1: Cohort 2 - GSK3965193 Dose 5/Dose 6/Dose 7/Placebo
Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 6 oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 7 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of placebo oral solution on Day 1 in Treatment Period 4. Dose 7 of GSK3965193 was higher than Dose 6 and Dose 6 was higher than Dose 5.
FG008
Part 2A: Placebo
Healthy participants received repeat doses of placebo oral solution twice daily (BID) for 14 days.
FG009
Part 2A: Cohort 5 - GSK3965193 Dose 9 BID
Healthy participants received repeat doses of GSK3965193 Dose 9 oral solution BID for 14 days. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
FG010
Part 2A: Cohort 3 - GSK3965193 Dose 5 BID
Healthy participants received repeat doses of GSK3965193 Dose 5 oral solution BID for 14 days. Dose 5 of GSK3965193 was higher than Dose 9 but lower than Dose 10.
FG011
Part 2A: Cohort 4 - GSK3965193 Dose 6 BID
Healthy participants received repeat doses of GSK3965193 Dose 6 oral solution BID for 14 days. Dose 6 of GSK3965193 was higher than Dose 10 but lower than Dose 7.
FG012
Part 2B: Cohort 6 - GSK3965193 Dose 10 Fasted/Fed
Healthy participants received GSK3965193 Dose 10 oral tablets under fasted condition in Treatment Period 1, followed by GSK3965193 Dose 10 oral tablets under fed condition in Treatment Period 2. Dose 10 of GSK3965193 was higher than Dose 5 but lower than Dose 6.
FG013
Part 2B: Cohort 6 - GSK3965193 Dose 10 Fed/Fasted
Healthy participants received GSK3965193 Dose 10 oral tablets under fed condition in Treatment Period 1, followed by GSK3965193 Dose 10 oral tablets under fasted condition in Treatment Period 2. Dose 10 of GSK3965193 was higher than Dose 5 but lower than Dose 6.
FG014
Part 3: Cohort 7 - Placebo
Participants living with chronic hepatitis B infection (PLWCHB) on stable nucleos(t)ide analog (NA) therapy received repeat doses of placebo oral tablets for 28 days. Participants who completed placebo monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen subcutaneous (SC) injection from Day 43.
FG015
Part 3: Cohort 7 - GSK3965193 Dose 9
PLWCHB on stable NA therapy received repeat doses of GSK3965193 Dose 9 oral tablets for 28 days. Participants who completed GSK3965193 monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen SC injection from Day 43. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
FG016
Part 4: Cohort 8 - Placebo + Bepirovirsen
PLWCHB on stable NA therapy were planned to receive placebo oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
FG017
Part 4: Cohort 8 - GSK3965193 + Bepirovirsen
PLWCHB on stable NA therapy were planned to receive GSK3965193 oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
FG0002 subjects
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Part 1, Cohort 1: Treatment Period 2
Type
Comment
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STARTED
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Part 1, Cohort 1: Treatment Period 3
Type
Comment
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STARTED
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Part 1, Cohort 1: Treatment Period 4
Type
Comment
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STARTED
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Part 1, Cohort 2: Treatment Period 1
Type
Comment
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STARTED
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FG004
NOT COMPLETED
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FG004
Type
Comment
Reasons
Adverse Event
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FG003
Part 1, Cohort 2: Treatment Period 2
Type
Comment
Milestone Data
STARTED
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FG0052 subjectsTwo new participants were enrolled to replace the withdrawn participants from Treatment Period 1.
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Part 1, Cohort 2: Treatment Period 3
Type
Comment
Milestone Data
STARTED
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FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Part 1, Cohort 2: Treatment Period 4
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0042 subjectsOne new participant was enrolled to replace the withdrawn participant from Treatment Period 3.
FG0052 subjectsOne new participant was enrolled to replace the withdrawn participant from Treatment Period 3.
FG0062 subjects
FG0072 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Part 2A, Cohorts 3, 4, 5
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0086 subjects
FG0096 subjects
FG0107 subjects
FG0114 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Part 2B, Cohort 6: Treatment Period 1
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0126 subjects
FG0137 subjects
FG0140 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Physician Decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Part 2B, Cohort 6: Treatment Period 2
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0126 subjects
FG0136 subjects
FG0140 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Part 3, Cohort 7
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0144 subjects
FG01514 subjects
FG0160 subjects
FG0170 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Ongoing in Optional Bepirovirsen Treatment Part at the time of analysis
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Part 4, Cohort 8
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
The study was terminated after completion of Part 3 as a strategic decision. Hence, no participants were enrolled in Part 4.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part 1: Cohort 1 - Placebo/GSK3965193 Dose 2/Dose 3/Dose 4
Healthy participants received a single dose of placebo oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 2 oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 3 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 4 oral solution on Day 1 in Treatment Period 4. Dose 4 of GSK3965193 was higher than Dose 3 and Dose 3 was higher than Dose 2.
BG001
Part 1: Cohort 1 - GSK3965193 Dose 1/Placebo/Dose 3/Dose 4
Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in Treatment Period 1; followed by a single dose of placebo oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 3 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 4 oral solution on Day 1 in Treatment Period 4. Dose 4 of GSK3965193 was higher than Dose 3 and Dose 3 was higher than Dose 1.
BG002
Part 1: Cohort 1 - GSK3965193 Dose 1/Dose 2/Placebo/Dose 4
Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 2 oral solution on Day 1 in Treatment Period 2; followed by a single dose of placebo oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 4 oral solution on Day 1 in Treatment Period 4. Dose 4 of GSK3965193 was higher than Dose 2 and Dose 2 was higher than Dose 1.
BG003
Part 1: Cohort 1 - GSK3965193 Dose 1/Dose 2/Dose 3/Placebo
Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 2 oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 3 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of placebo oral solution on Day 1 in Treatment Period 4. Dose 3 of GSK3965193 was higher than Dose 2 and Dose 2 was higher than Dose 1.
BG004
Part 1: Cohort 2 - Placebo/GSK3965193 Dose 6/Dose 7/Dose 8
Healthy participants received a single dose of placebo oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 6 oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 7 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 8 oral solution on Day 1 in Treatment Period 4. Dose 8 of GSK3965193 was higher than Dose 7 and Dose 7 was higher than Dose 6.
BG005
Part 1: Cohort 2 - GSK3965193 Dose 5/Placebo/Dose 7/Dose 8
Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in Treatment Period 1; followed by a single dose of placebo oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 7 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 8 oral solution on Day 1 in Treatment Period 4. Dose 8 of GSK3965193 was higher than Dose 7 and Dose 7 was higher than Dose 5.
BG006
Part 1: Cohort 2 - GSK3965193 Dose 5/Dose 6/Placebo/Dose 8
Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 6 oral solution on Day 1 in Treatment Period 2; followed by a single dose of placebo oral solution on Day 1 in Treatment Period 3; further followed by a single dose of GSK3965193 Dose 8 oral solution on Day 1 in Treatment Period 4. Dose 8 of GSK3965193 was higher than Dose 6 and Dose 6 was higher than Dose 5.
BG007
Part 1: Cohort 2 - GSK3965193 Dose 5/Dose 6/Dose 7/Placebo
Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in Treatment Period 1; followed by a single dose of GSK3965193 Dose 6 oral solution on Day 1 in Treatment Period 2; followed by a single dose of GSK3965193 Dose 7 oral solution on Day 1 in Treatment Period 3; further followed by a single dose of placebo oral solution on Day 1 in Treatment Period 4. Dose 7 of GSK3965193 was higher than Dose 6 and Dose 6 was higher than Dose 5.
BG008
Part 2A: Placebo
Healthy participants received repeat doses of placebo oral solution twice daily (BID) for 14 days.
BG009
Part 2A: Cohort 5 - GSK3965193 Dose 9 BID
Healthy participants received repeat doses of GSK3965193 Dose 9 oral solution BID for 14 days. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
BG010
Part 2A: Cohort 3 - GSK3965193 Dose 5 BID
Healthy participants received repeat doses of GSK3965193 Dose 5 oral solution BID for 14 days. Dose 5 of GSK3965193 was higher than Dose 9 but lower than Dose 10.
BG011
Part 2A: Cohort 4 - GSK3965193 Dose 6 BID
Healthy participants received repeat doses of GSK3965193 Dose 6 oral solution BID for 14 days. Dose 6 of GSK3965193 was higher than Dose 10 but lower than Dose 7.
BG012
Part 2B: Cohort 6 - GSK3965193 Dose 10 Fasted/Fed
Healthy participants received GSK3965193 Dose 10 oral tablets under fasted condition in Treatment Period 1, followed by GSK3965193 Dose 10 oral tablets under fed condition in Treatment Period 2. Dose 10 of GSK3965193 was higher than Dose 5 but lower than Dose 6.
BG013
Part 2B: Cohort 6 - GSK3965193 Dose 10 Fed/Fasted
Healthy participants received GSK3965193 Dose 10 oral tablets under fed condition in Treatment Period 1, followed by GSK3965193 Dose 10 oral tablets under fasted condition in Treatment Period 2. Dose 10 of GSK3965193 was higher than Dose 5 but lower than Dose 6.
BG014
Part 3: Cohort 7 - Placebo
Participants living with chronic hepatitis B infection (PLWCHB) on stable nucleos(t)ide analog (NA) therapy received repeat doses of placebo oral tablets for 28 days. Participants who completed placebo monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen subcutaneous (SC) injection from Day 43.
BG015
Part 3: Cohort 7 - GSK3965193 Dose 9
PLWCHB on stable NA therapy received repeat doses of GSK3965193 Dose 9 oral tablets for 28 days. Participants who completed GSK3965193 monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen SC injection from Day 43. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
BG016
Part 4: Cohort 8 - Placebo + Bepirovirsen
PLWCHB on stable NA therapy were planned to receive placebo oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
BG017
Part 4: Cohort 8 - GSK3965193 + Bepirovirsen
PLWCHB on stable NA therapy were planned to receive GSK3965193 oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
BG018
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0002
BG0012
BG0022
BG0032
BG0043
BG0055
BG0062
BG0072
BG0086
BG0096
BG0107
BG0114
BG0126
BG0137
BG0144
BG01514
BG0160
BG0170
BG01874
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
18 to 55 years
Title
Measurements
BG0002
BG0012
BG0022
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0000
BG0010
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
ASIAN
Title
Measurements
BG0000
BG0012
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Treatment Emergent Adverse Events (STEAEs), and Treatment Withdrawals Due to TEAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE was considered treatment emergent if the AE onset date was on or after study intervention start date (i.e., Day 1) till Day 5 after study intervention administration. Any AE which started post Day 5 of study intervention administration was not considered as TEAE.
Safety population included all participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
From the start of study intervention (Day 1) up to 12 weeks
ID
Title
Description
OG000
Part 1: Cohorts 1 and 2 - Placebo
Healthy participants from Part 1: Cohorts 1 and 2 received a single dose of placebo oral solution on Day 1 of either Treatment Periods 1, 2, 3, or 4.
OG001
Part 1: Cohort 1 - GSK3965193 Dose 1
Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 1 was the lowest dose in Cohort 1.
OG002
Part 1: Cohort 1 - GSK3965193 Dose 2
Healthy participants received a single dose of GSK3965193 Dose 2 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 2 was higher than Dose 1 but lower than Dose 3.
OG003
Part 1: Cohort 1 - GSK3965193 Dose 3
Healthy participants received a single dose of GSK3965193 Dose 3 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 3 was higher than Dose 2 but lower than Dose 4.
OG004
Part 1: Cohort 1 - GSK3965193 Dose 4
Healthy participants received a single dose of GSK3965193 Dose 4 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 4 was the highest dose in Cohort 1.
OG005
Part 1: Cohort 2 - GSK3965193 Dose 5
Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 5 was the lowest dose in Cohort 2 but was higher than Dose 4 of Cohort 1.
OG006
Part 1: Cohort 2 - GSK3965193 Dose 6
Healthy participants received a single dose of GSK3965193 Dose 6 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 6 was higher than Dose 5 but lower than Dose 7.
Units
Counts
Participants
OG00016
OG0016
OG0026
OG003
Title
Denominators
Categories
Any TEAE
Title
Measurements
OG0002
OG0013
OG0021
OG003
Primary
Part 2A: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals Due to TEAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE was considered treatment emergent if the AE onset date was on or after study intervention start date.
Safety population included all participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
From the start of study intervention (Day 1) up to 6 weeks
ID
Title
Description
OG000
Part 2A: Placebo
Healthy participants received repeat doses of placebo oral solution twice daily (BID) for 14 days.
OG001
Part 2A: Cohort 5 - GSK3965193 Dose 9 BID
Healthy participants received repeat doses of GSK3965193 Dose 9 oral solution BID for 14 days. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
OG002
Primary
Part 2B: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals Due to TEAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE was considered treatment emergent if the AE onset date was on or after study intervention start date (i.e., Day 1) till Day 5 after study intervention administration. Any AE which started post Day 5 of study intervention administration was not considered as TEAE.
Safety population included all participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
From the start of study intervention (Day 1) up to 9 weeks
ID
Title
Description
OG000
Part 2B: Cohort 6 - GSK3965193 Dose 10 Fasted
Healthy participants received GSK3965193 Dose 10 oral tablets under fasted condition in either Treatment Periods 1 or 2. Dose 10 of GSK3965193 was higher than Dose 5 but lower than Dose 6.
OG001
Part 2B: Cohort 6 - GSK3965193 Dose 10 Fed
Primary
Part 3: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals Due to TEAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE was considered treatment emergent if the AE onset or worsen date was on or after study intervention start date. Data for the placebo or GSK3965193 monotherapy phase were presented.
Safety population included all participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
From the start of study intervention (Day 1) up to 6 weeks
ID
Title
Description
OG000
Part 3: Cohort 7 - Placebo
Participants living with chronic hepatitis B infection (PLWCHB) on stable nucleos(t)ide analog (NA) therapy received repeat doses of placebo oral tablets for 28 days. Participants who completed placebo monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen subcutaneous (SC) injection from Day 43.
OG001
Part 3: Cohort 7 - GSK3965193 Dose 9
Primary
Part 4: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals Due to TEAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator. An AE would be considered treatment emergent if the AE onset or worsen date was on or after study intervention start date.
The study was terminated after completion of Part 3 as a strategic decision. Hence, no participants were enrolled in Part 4.
Posted
From the start of study intervention (Day 1) up to 48 weeks
ID
Title
Description
OG000
Part 4: Cohort 8 - Placebo + Bepirovirsen
PLWCHB on stable NA therapy were planned to receive placebo oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
OG001
Part 4: Cohort 8 - GSK3965193 + Bepirovirsen
PLWCHB on stable NA therapy were planned to receive GSK3965193 oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
Primary
Part 1: Number of Participants With Clinically Significant Hematology and Clinical Chemistry Parameters
Blood samples were collected to analyze hematology and clinical chemistry parameters: platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, RBC indices (mean corpuscular volume [MCV] and mean corpuscular hemoglobin [MCH]), white blood cell (WBC) count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), blood urea nitrogen (BUN), creatinine, glucose (non-fasting), potassium, sodium, calcium, aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT), alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Clinical significance of laboratory parameters was determined by the investigator.
Safety population included all participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
At Day 2
ID
Title
Description
OG000
Part 1: Cohorts 1 and 2 - Placebo
Healthy participants from Part 1: Cohorts 1 and 2 received a single dose of placebo oral solution on Day 1 of either Treatment Periods 1, 2, 3, or 4.
OG001
Part 1: Cohort 1 - GSK3965193 Dose 1
Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 1 was the lowest dose in Cohort 1.
Primary
Part 2A: Number of Participants With Clinically Significant Hematology, Clinical Chemistry, and Urinalysis Parameters
Blood samples were collected to analyze hematology and clinical chemistry parameters: platelet count, RBC count, hemoglobin, hematocrit, RBC indices (MCV and MCH), WBC count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), BUN, creatinine, glucose (non-fasting), potassium, sodium, calcium, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Urine samples were analyzed using automated urinalysis or urine dipstick. Microscopic examination was performed if abnormal blood or protein was present in the urine sample. Clinical significance of laboratory parameters was determined by the investigator.
Safety population included all participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
Up to 21 days
ID
Title
Description
OG000
Part 2A: Placebo
Healthy participants received repeat doses of placebo oral solution twice daily (BID) for 14 days.
OG001
Part 2A: Cohort 5 - GSK3965193 Dose 9 BID
Healthy participants received repeat doses of GSK3965193 Dose 9 oral solution BID for 14 days. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
OG002
Primary
Part 2B: Number of Participants With Clinically Significant Hematology, Clinical Chemistry, and Urinalysis Parameters
Blood samples were collected to analyze hematology and clinical chemistry parameters: platelet count, RBC count, hemoglobin, hematocrit, RBC indices (MCV and MCH), WBC count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), BUN, creatinine, glucose (non-fasting), potassium, sodium, calcium, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Urine samples were analyzed using automated urinalysis or urine dipstick. Microscopic examination was performed if abnormal blood or protein was present in the urine sample. Clinical significance of laboratory parameters was determined by the investigator.
Safety population included all participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
Up to 9 weeks
ID
Title
Description
OG000
Part 2B: Cohort 6 - GSK3965193 Dose 10 Fasted
Healthy participants received GSK3965193 Dose 10 oral tablets under fasted condition in either Treatment Periods 1 or 2. Dose 10 of GSK3965193 was higher than Dose 5 but lower than Dose 6.
OG001
Part 2B: Cohort 6 - GSK3965193 Dose 10 Fed
Healthy participants received GSK3965193 Dose 10 oral tablets under fed condition in either Treatment Periods 1 or 2. Dose 10 of GSK3965193 was higher than Dose 5 but lower than Dose 6.
Primary
Part 3: Number of Participants With Clinically Significant Hematology and Clinical Chemistry Parameters
Blood samples were collected to analyze hematology and clinical chemistry parameters: platelet count, RBC count, hemoglobin, hematocrit, RBC indices (MCV and MCH), WBC count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), BUN, creatinine, glucose (non-fasting), potassium, sodium, calcium, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Clinical significance of laboratory parameters was determined by the investigator. Data for the placebo or GSK3965193 monotherapy phase were presented.
Safety population included all participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
Up to 35 days
ID
Title
Description
OG000
Part 3: Cohort 7 - Placebo
Participants living with chronic hepatitis B infection (PLWCHB) on stable nucleos(t)ide analog (NA) therapy received repeat doses of placebo oral tablets for 28 days. Participants who completed placebo monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen subcutaneous (SC) injection from Day 43.
OG001
Part 3: Cohort 7 - GSK3965193 Dose 9
PLWCHB on stable NA therapy received repeat doses of GSK3965193 Dose 9 oral tablets for 28 days. Participants who completed GSK3965193 monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen SC injection from Day 43. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
Primary
Part 3: Number of Participants With Clinically Significant Urinalysis Parameters
Urine samples were analyzed using automated urinalysis or urine dipstick. Microscopic examination was performed if abnormal blood or protein was present in the urine sample. Clinical significance of laboratory parameters was determined by the investigator. Data for the placebo or GSK3965193 monotherapy phase were presented.
Safety population included all participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
Up to 28 days
ID
Title
Description
OG000
Part 3: Cohort 7 - Placebo
Participants living with chronic hepatitis B infection (PLWCHB) on stable nucleos(t)ide analog (NA) therapy received repeat doses of placebo oral tablets for 28 days. Participants who completed placebo monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen subcutaneous (SC) injection from Day 43.
OG001
Part 3: Cohort 7 - GSK3965193 Dose 9
PLWCHB on stable NA therapy received repeat doses of GSK3965193 Dose 9 oral tablets for 28 days. Participants who completed GSK3965193 monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen SC injection from Day 43. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
Primary
Part 4: Number of Participants With Clinically Significant Hematology, Clinical Chemistry, and Urinalysis Parameters
Blood samples were planned to be collected to analyze hematology and clinical chemistry parameters: platelet count, RBC count, hemoglobin, hematocrit, RBC indices (MCV and MCH), WBC count with differential (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), BUN, creatinine, glucose (non-fasting), potassium, sodium, calcium, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin, indirect bilirubin, direct bilirubin, total protein, and albumin. Urine samples were planned to be analyzed using automated urinalysis or urine dipstick. Microscopic examination was planned to be performed if abnormal blood or protein was present in the urine sample. Clinical significance of laboratory parameters would be determined by the investigator.
The study was terminated after completion of Part 3 as a strategic decision. Hence, no participants were enrolled in Part 4.
Posted
Up to 48 weeks
ID
Title
Description
OG000
Part 4: Cohort 8 - Placebo + Bepirovirsen
PLWCHB on stable NA therapy were planned to receive placebo oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
OG001
Part 4: Cohort 8 - GSK3965193 + Bepirovirsen
PLWCHB on stable NA therapy were planned to receive GSK3965193 oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
Primary
Part 1: Number of Participants With Clinically Significant Vital Sign Findings
Vital signs included systolic blood pressure (SBP) and diastolic blood pressure (DBP), pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings was determined by the investigator.
Safety population included all participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
Up to 12 weeks
ID
Title
Description
OG000
Part 1: Cohorts 1 and 2 - Placebo
Healthy participants from Part 1: Cohorts 1 and 2 received a single dose of placebo oral solution on Day 1 of either Treatment Periods 1, 2, 3, or 4.
OG001
Part 1: Cohort 1 - GSK3965193 Dose 1
Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 1 was the lowest dose in Cohort 1.
OG002
Part 1: Cohort 1 - GSK3965193 Dose 2
Healthy participants received a single dose of GSK3965193 Dose 2 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 2 was higher than Dose 1 but lower than Dose 3.
Primary
Part 2A: Number of Participants With Clinically Significant Vital Sign Findings
Vital signs included SBP and DBP, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings was determined by the investigator.
Safety population included all participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
Up to 21 days
ID
Title
Description
OG000
Part 2A: Placebo
Healthy participants received repeat doses of placebo oral solution twice daily (BID) for 14 days.
OG001
Part 2A: Cohort 5 - GSK3965193 Dose 9 BID
Healthy participants received repeat doses of GSK3965193 Dose 9 oral solution BID for 14 days. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
OG002
Part 2A: Cohort 3 - GSK3965193 Dose 5 BID
Healthy participants received repeat doses of GSK3965193 Dose 5 oral solution BID for 14 days. Dose 5 of GSK3965193 was higher than Dose 9 but lower than Dose 10.
OG003
Part 2A: Cohort 4 - GSK3965193 Dose 6 BID
Primary
Part 2B: Number of Participants With Clinically Significant Vital Sign Findings
Vital signs included SBP and DBP, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings was determined by the investigator.
Safety population included all participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
Up to 9 weeks
ID
Title
Description
OG000
Part 2B: Cohort 6 - GSK3965193 Dose 10 Fasted
Healthy participants received GSK3965193 Dose 10 oral tablets under fasted condition in either Treatment Periods 1 or 2. Dose 10 of GSK3965193 was higher than Dose 5 but lower than Dose 6.
OG001
Part 2B: Cohort 6 - GSK3965193 Dose 10 Fed
Healthy participants received GSK3965193 Dose 10 oral tablets under fed condition in either Treatment Periods 1 or 2. Dose 10 of GSK3965193 was higher than Dose 5 but lower than Dose 6.
Units
Counts
Participants
Primary
Part 3: Number of Participants With Clinically Significant Vital Sign Findings
Vital signs included temperature, SBP and DBP, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings was determined by the investigator. Data for the placebo or GSK3965193 monotherapy phase were presented.
Safety population included all participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
Up to 35 days
ID
Title
Description
OG000
Part 3: Cohort 7 - Placebo
Participants living with chronic hepatitis B infection (PLWCHB) on stable nucleos(t)ide analog (NA) therapy received repeat doses of placebo oral tablets for 28 days. Participants who completed placebo monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen subcutaneous (SC) injection from Day 43.
OG001
Part 3: Cohort 7 - GSK3965193 Dose 9
PLWCHB on stable NA therapy received repeat doses of GSK3965193 Dose 9 oral tablets for 28 days. Participants who completed GSK3965193 monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen SC injection from Day 43. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
Primary
Part 4: Number of Participants With Clinically Significant Vital Signs Findings
Vital signs were planned to include temperature, SBP and DBP, pulse and respiratory rate and were planned to be measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of the vital sign findings would be determined by the investigator.
The study was terminated after completion of Part 3 as a strategic decision. Hence, no participants were enrolled in Part 4.
Posted
Up to 48 weeks
ID
Title
Description
OG000
Part 4: Cohort 8 - Placebo + Bepirovirsen
PLWCHB on stable NA therapy were planned to receive placebo oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
OG001
Part 4: Cohort 8 - GSK3965193 + Bepirovirsen
PLWCHB on stable NA therapy were planned to receive GSK3965193 oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
Units
Counts
Participants
Primary
Part 1: Number of Participants With Clinically Significant Electrocardiogram [ECG] Findings
A 12-lead ECG was recorded with the participant in a semi-supine position after 5 minutes of rest using an ECG machine. The parameters collected were PR, QRS, QT, and corrected QT (QTc) intervals. Clinical significance of ECG parameters was determined by the investigator.
Safety population included all participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
Up to 12 weeks
ID
Title
Description
OG000
Part 1: Cohorts 1 and 2 - Placebo
Healthy participants from Part 1: Cohorts 1 and 2 received a single dose of placebo oral solution on Day 1 of either Treatment Periods 1, 2, 3, or 4.
OG001
Part 1: Cohort 1 - GSK3965193 Dose 1
Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 1 was the lowest dose in Cohort 1.
OG002
Part 1: Cohort 1 - GSK3965193 Dose 2
Healthy participants received a single dose of GSK3965193 Dose 2 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 2 was higher than Dose 1 but lower than Dose 3.
Primary
Part 2A: Number of Participants With Clinically Significant ECG Findings
A 12-lead ECG was recorded with the participant in a semi-supine position after 5 minutes of rest using an ECG machine. The parameters collected were PR, QRS, QT, and QTc intervals. Clinical significance of ECG parameters was determined by the investigator.
Safety population included all participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
Up to 21 days
ID
Title
Description
OG000
Part 2A: Placebo
Healthy participants received repeat doses of placebo oral solution twice daily (BID) for 14 days.
OG001
Part 2A: Cohort 5 - GSK3965193 Dose 9 BID
Healthy participants received repeat doses of GSK3965193 Dose 9 oral solution BID for 14 days. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
OG002
Part 2A: Cohort 3 - GSK3965193 Dose 5 BID
Healthy participants received repeat doses of GSK3965193 Dose 5 oral solution BID for 14 days. Dose 5 of GSK3965193 was higher than Dose 9 but lower than Dose 10.
OG003
Primary
Part 3: Number of Participants With Clinically Significant ECG Findings
A 12-lead ECG was recorded with the participant in a semi-supine position after 5 minutes of rest using an ECG machine. The parameters collected were PR, QRS, QT, and QTc intervals. Clinical significance of ECG parameters was determined by the investigator. Data for the placebo or GSK3965193 monotherapy phase were presented.
Safety population included all participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
Up to 35 days
ID
Title
Description
OG000
Part 3: Cohort 7 - Placebo
Participants living with chronic hepatitis B infection (PLWCHB) on stable nucleos(t)ide analog (NA) therapy received repeat doses of placebo oral tablets for 28 days. Participants who completed placebo monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen subcutaneous (SC) injection from Day 43.
OG001
Part 3: Cohort 7 - GSK3965193 Dose 9
PLWCHB on stable NA therapy received repeat doses of GSK3965193 Dose 9 oral tablets for 28 days. Participants who completed GSK3965193 monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen SC injection from Day 43. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
Primary
Part 4: Number of Participants With Clinically Significant ECG Findings
A 12-lead ECG was planned to be recorded with the participant in a semi-supine position after 5 minutes of rest using an ECG machine. The parameters planned to be collected were PR, QRS, QT, and QTc intervals. Clinical significance of ECG findings would be determined by the investigator.
The study was terminated after completion of Part 3 as a strategic decision. Hence, no participants were enrolled in Part 4.
Posted
Up to 25 weeks
ID
Title
Description
OG000
Part 4: Cohort 8 - Placebo + Bepirovirsen
PLWCHB on stable NA therapy were planned to receive placebo oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
OG001
Part 4: Cohort 8 - GSK3965193 + Bepirovirsen
PLWCHB on stable NA therapy were planned to receive GSK3965193 oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
Units
Counts
Participants
Primary
Part 2A: Number of Participants With Changes in Sensory Nerve Conduction at Day 7
Sensory nerve conduction testing was performed to detect neuropathy in participants. Nerve conduction velocity (NCV) and nerve conduction amplitude were determined. Sensory nerve conduction studies at Baseline were collected twice, one at the time of screen and one prior to dosing. Mean (arithmetic mean) of two measurements were considered as Baseline. Number of participants with 25 percent (%) decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 7 was reported.
Safety population included all participants who received at least one dose of study treatment. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field.
Posted
Count of Participants
Participants
Baseline and Day 7
ID
Title
Description
OG000
Part 2A: Placebo
Healthy participants received repeat doses of placebo oral solution twice daily (BID) for 14 days.
OG001
Part 2A: Cohort 5 - GSK3965193 Dose 9 BID
Healthy participants received repeat doses of GSK3965193 Dose 9 oral solution BID for 14 days. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
OG002
Part 2A: Cohort 3 - GSK3965193 Dose 5 BID
Primary
Part 2A: Number of Participants With Changes in Sensory Nerve Conduction at Day 14
Sensory nerve conduction testing was performed to detect neuropathy in participants. NCV and nerve conduction amplitude were determined. Sensory nerve conduction studies at Baseline were collected twice, one at the time of screen and one prior to dosing. Mean (arithmetic mean) of two measurements were considered as Baseline. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 14 was reported.
Safety population included all participants who received at least one dose of study treatment. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field. Treatment to Cohort 4 was discontinued before Day 14 due to adverse events. Hence, 'Overall Number of Participants Analyzed' for this arm is "0".
Posted
Count of Participants
Participants
Baseline and Day 14
ID
Title
Description
OG000
Part 2A: Placebo
Healthy participants received repeat doses of placebo oral solution twice daily (BID) for 14 days.
OG001
Part 2A: Cohort 5 - GSK3965193 Dose 9 BID
Healthy participants received repeat doses of GSK3965193 Dose 9 oral solution BID for 14 days. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
Primary
Part 2A: Number of Participants With Changes in Sensory Nerve Conduction at Day 42
Sensory nerve conduction testing was performed to detect neuropathy in participants. NCV and nerve conduction amplitude were determined. Sensory nerve conduction studies at Baseline were collected twice, one at the time of screen and one prior to dosing. Mean (arithmetic mean) of two measurements were considered as Baseline. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 42 was reported.
Safety population included all participants who received at least one dose of study treatment. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field. Treatment to Cohort 4 was discontinued before Day 14 due to adverse events. Hence, 'Overall Number of Participants Analyzed' for this arm is "0".
Posted
Count of Participants
Participants
Baseline and Day 42
ID
Title
Description
OG000
Part 2A: Placebo
Healthy participants received repeat doses of placebo oral solution twice daily (BID) for 14 days.
OG001
Part 2A: Cohort 5 - GSK3965193 Dose 9 BID
Healthy participants received repeat doses of GSK3965193 Dose 9 oral solution BID for 14 days. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
Primary
Part 3: Number of Participants With Changes in Sensory Nerve Conduction at Day 15
Sensory nerve conduction testing was performed to detect neuropathy in participants. NCV and nerve conduction amplitude were determined. The best measurement out of Screening and Day -1 was considered as Baseline, best being the higher measurement. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 15 for the placebo or GSK3965193 monotherapy phase was reported.
Safety population included all participants who received at least one dose of study treatment.
Posted
Count of Participants
Participants
Baseline and Day 15
ID
Title
Description
OG000
Part 3: Cohort 7 - Placebo
Participants living with chronic hepatitis B infection (PLWCHB) on stable nucleos(t)ide analog (NA) therapy received repeat doses of placebo oral tablets for 28 days. Participants who completed placebo monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen subcutaneous (SC) injection from Day 43.
OG001
Part 3: Cohort 7 - GSK3965193 Dose 9
PLWCHB on stable NA therapy received repeat doses of GSK3965193 Dose 9 oral tablets for 28 days. Participants who completed GSK3965193 monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen SC injection from Day 43. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
Primary
Part 3: Number of Participants With Changes in Sensory Nerve Conduction at Day 29
Sensory nerve conduction testing was performed to detect neuropathy in participants. NCV and nerve conduction amplitude were determined. The best measurement out of Screening and Day -1 was considered as Baseline, best being the higher measurement. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from Baseline at Day 29 for the placebo or GSK3965193 monotherapy phase was reported.
Safety population included all participants who received at least one dose of study treatment. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field.
Posted
Count of Participants
Participants
Baseline and Day 29
ID
Title
Description
OG000
Part 3: Cohort 7 - Placebo
Participants living with chronic hepatitis B infection (PLWCHB) on stable nucleos(t)ide analog (NA) therapy received repeat doses of placebo oral tablets for 28 days. Participants who completed placebo monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen subcutaneous (SC) injection from Day 43.
OG001
Part 3: Cohort 7 - GSK3965193 Dose 9
PLWCHB on stable NA therapy received repeat doses of GSK3965193 Dose 9 oral tablets for 28 days. Participants who completed GSK3965193 monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen SC injection from Day 43. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
Primary
Part 4: Number of Participants With Changes in Sensory Nerve Conduction
Sensory nerve conduction testing was planned to be performed to detect neuropathy in participants. NCV and nerve conduction amplitude were planned to be determined. Number of participants with 25% decrease in NCV and 50% decrease in nerve conduction amplitude from baseline was planned to be reported.
The study was terminated after completion of Part 3 as a strategic decision. Hence, no participants were enrolled in Part 4.
Posted
Baseline up to 29 days
ID
Title
Description
OG000
Part 4: Cohort 8 - Placebo + Bepirovirsen
PLWCHB on stable NA therapy were planned to receive placebo oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
OG001
Part 4: Cohort 8 - GSK3965193 + Bepirovirsen
PLWCHB on stable NA therapy were planned to receive GSK3965193 oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
Units
Counts
Participants
Primary
Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3965193 Following Single Dose Administration
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
PK parameter population included all participants in the Safety population who received an active study treatment and had at least 1 non-missing PK assessment (non-quantifiable [NQ] values were considered as non-missing values) and had evaluable parameters estimated.
Posted
Geometric Mean
Geometric Coefficient of Variation
Hours*nanograms per milliliter
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours (h) post-dose
ID
Title
Description
OG000
Part 1: Cohort 1 - GSK3965193 Dose 1
Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 1 was the lowest dose in Cohort 1.
OG001
Part 1: Cohort 1 - GSK3965193 Dose 2
Healthy participants received a single dose of GSK3965193 Dose 2 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 2 was higher than Dose 1 but lower than Dose 3.
OG002
Part 1: Cohort 1 - GSK3965193 Dose 3
Primary
Part 2A: AUC Over the Dosing Interval Tau (AUC[0-tau]) of GSK3965193 Following Repeat Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods. As the dosing interval Tau was 12 hours, AUC(0-tau) is the same as AUC from time zero to 12 hours after dosing (AUC[0-12]).
PK parameter population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field. 'Number Analyzed' signifies participants evaluable for the specified categories. Treatment to Cohort 4 was discontinued before Day 14 due to adverse events. Hence, 'Number Analyzed' for this arm is "0" for Day 14.
Posted
Geometric Mean
Geometric Coefficient of Variation
Hours*nanograms per milliliter
Pre-dose and 15 minutes (min), 30 min, 1 h, 2 h, 3 h, 4, h, 8 h, and 12 h post-first dose on Day 1; pre-dose and 15 min, 30 min, 1 h, 2h, 4 h, 8 h, and 12 h post-first dose on Day 14
ID
Title
Description
OG000
Part 2A: Cohort 5 - GSK3965193 Dose 9 BID
Healthy participants received repeat doses of GSK3965193 Dose 9 oral solution BID for 14 days. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
OG001
Part 2A: Cohort 3 - GSK3965193 Dose 5 BID
Healthy participants received repeat doses of GSK3965193 Dose 5 oral solution BID for 14 days. Dose 5 of GSK3965193 was higher than Dose 9 but lower than Dose 10.
Primary
Part 1: Maximum Observed Concentration (Cmax) of GSK3965193 Following Single Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
PK parameter population included all participants in the Safety population who received an active study treatment and had at least 1 non-missing PK assessment (NQ values were considered as non-missing values) and had evaluable parameters estimated.
Posted
Geometric Mean
Geometric Coefficient of Variation
Nanograms per milliliter
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post-dose
ID
Title
Description
OG000
Part 1: Cohort 1 - GSK3965193 Dose 1
Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 1 was the lowest dose in Cohort 1.
OG001
Part 1: Cohort 1 - GSK3965193 Dose 2
Healthy participants received a single dose of GSK3965193 Dose 2 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 2 was higher than Dose 1 but lower than Dose 3.
OG002
Part 1: Cohort 1 - GSK3965193 Dose 3
Healthy participants received a single dose of GSK3965193 Dose 3 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 3 was higher than Dose 2 but lower than Dose 4.
Primary
Part 2A: Cmax of GSK3965193 Following Repeat Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
PK parameter population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field. 'Number Analyzed' signifies participants evaluable for the specified categories. Treatment to Cohort 4 was discontinued before Day 14 due to adverse events. Hence, 'Number Analyzed' for this arm is "0" for Day 14.
Posted
Geometric Mean
Geometric Coefficient of Variation
Nanograms per milliliter
Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4, h, 8 h, and 12 h post-first dose on Day 1; pre-morning dose on Days 2 through 6 and Days 12 through 13; pre-dose and 15 min, 30 min, 1 h, 2h, 4 h, 8 h, 12 h, 24 h, 48 h, and 72 h post-first dose on Day 14
ID
Title
Description
OG000
Part 2A: Cohort 5 - GSK3965193 Dose 9 BID
Healthy participants received repeat doses of GSK3965193 Dose 9 oral solution BID for 14 days. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
OG001
Part 2A: Cohort 3 - GSK3965193 Dose 5 BID
Healthy participants received repeat doses of GSK3965193 Dose 5 oral solution BID for 14 days. Dose 5 of GSK3965193 was higher than Dose 9 but lower than Dose 10.
Primary
Part 1: Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK3965193 Following Single Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
PK parameter population included all participants in the Safety population who received an active study treatment and had at least 1 non-missing PK assessment (NQ values were considered as non-missing values) and had evaluable parameters estimated.
Posted
Median
Full Range
Hours
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post-dose
ID
Title
Description
OG000
Part 1: Cohort 1 - GSK3965193 Dose 1
Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 1 was the lowest dose in Cohort 1.
OG001
Part 1: Cohort 1 - GSK3965193 Dose 2
Healthy participants received a single dose of GSK3965193 Dose 2 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 2 was higher than Dose 1 but lower than Dose 3.
OG002
Part 1: Cohort 1 - GSK3965193 Dose 3
Healthy participants received a single dose of GSK3965193 Dose 3 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 3 was higher than Dose 2 but lower than Dose 4.
Primary
Part 2A: Tmax of GSK3965193 Following Repeat Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
PK parameter population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field. 'Number Analyzed' signifies participants evaluable for the specified categories. Treatment to Cohort 4 was discontinued before Day 14 due to adverse events. Hence, 'Number Analyzed' for this arm is "0" for Day 14.
Posted
Median
Full Range
Hours
Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4, h, 8 h, and 12 h post-first dose on Day 1; pre-morning dose on Days 2 through 6 and Days 12 through 13; pre-dose and 15 min, 30 min, 1 h, 2h, 4 h, 8 h, 12 h, 24 h, 48 h, and 72 h post-first dose on Day 14
ID
Title
Description
OG000
Part 2A: Cohort 5 - GSK3965193 Dose 9 BID
Healthy participants received repeat doses of GSK3965193 Dose 9 oral solution BID for 14 days. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
OG001
Part 2A: Cohort 3 - GSK3965193 Dose 5 BID
Healthy participants received repeat doses of GSK3965193 Dose 5 oral solution BID for 14 days. Dose 5 of GSK3965193 was higher than Dose 9 but lower than Dose 10.
Primary
Part 1: Apparent Terminal Half-life (T1/2) of GSK3965193 Following Single Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
PK parameter population included all participants in the Safety population who received an active study treatment and had at least 1 non-missing PK assessment (NQ values were considered as non-missing values) and had evaluable parameters estimated.
Posted
Mean
Standard Deviation
Hours
Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post-dose
ID
Title
Description
OG000
Part 1: Cohort 1 - GSK3965193 Dose 1
Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 1 was the lowest dose in Cohort 1.
OG001
Part 1: Cohort 1 - GSK3965193 Dose 2
Healthy participants received a single dose of GSK3965193 Dose 2 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 2 was higher than Dose 1 but lower than Dose 3.
OG002
Part 1: Cohort 1 - GSK3965193 Dose 3
Healthy participants received a single dose of GSK3965193 Dose 3 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 3 was higher than Dose 2 but lower than Dose 4.
Primary
Part 2A: T1/2 of GSK3965193 Following Repeat Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
PK parameter population. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field. 'Number Analyzed' signifies participants evaluable for the specified categories. Treatment to Cohort 4 was discontinued before Day 14 due to adverse events. Hence, 'Number Analyzed' for this arm is "0" for Day 14.
Posted
Mean
Standard Deviation
Hours
Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4, h, 8 h, and 12 h post-first dose on Day 1; pre-morning dose on Days 2 through 6 and Days 12 through 13; pre-dose and 15 min, 30 min, 1 h, 2h, 4 h, 8 h, 12 h, 24 h, 48 h, and 72 h post-first dose on Day 14
ID
Title
Description
OG000
Part 2A: Cohort 5 - GSK3965193 Dose 9 BID
Healthy participants received repeat doses of GSK3965193 Dose 9 oral solution BID for 14 days. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
OG001
Part 2A: Cohort 3 - GSK3965193 Dose 5 BID
Healthy participants received repeat doses of GSK3965193 Dose 5 oral solution BID for 14 days. Dose 5 of GSK3965193 was higher than Dose 9 but lower than Dose 10.
Primary
Part 3: Maximum Reduction of Serum HBsAg Levels From Baseline
Blood samples were collected from participants to assess HBsAg levels for the placebo or GSK3965193 monotherapy phase. Baseline was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Posterior mean and associated 95 percent (%) credible interval were derived for maximum reduction of serum HBsAg levels from Baseline using Bayesian mixed model repeated measures. The data presented are mean referring to posterior mean, with 95% confidence interval referring to 95% credible interval.
Pharmacodynamic (PD) population included all participants in Safety population who had at least one non-missing PD assessment and had neither taken any prohibited medication nor participated in previous clinical studies that were prohibited, as defined in protocol exclusion criteria, which might affect the efficacy assessment. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field.
Posted
Mean
95% Confidence Interval
Log10 international units per milliliter
From Baseline (Pre-dose on Day 1) up to 6 weeks
ID
Title
Description
OG000
Part 3: Cohort 7 - Placebo
Participants living with chronic hepatitis B infection (PLWCHB) on stable nucleos(t)ide analog (NA) therapy received repeat doses of placebo oral tablets for 28 days. Participants who completed placebo monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen subcutaneous (SC) injection from Day 43.
Primary
Part 4: Number of Participants Achieving Complete Response
Blood samples were planned to be collected to assess HBsAg and hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Complete response is defined HBsAg and HBV DNA below lower limit of quantification (LLOQ) for 6 consecutive months after the planned end of treatment.
The study was terminated after completion of Part 3 as a strategic decision. Hence, no participants were enrolled in Part 4.
Posted
Up to 48 weeks
ID
Title
Description
OG000
Part 4: Cohort 8 - Placebo + Bepirovirsen
PLWCHB on stable NA therapy were planned to receive placebo oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
OG001
Part 4: Cohort 8 - GSK3965193 + Bepirovirsen
PLWCHB on stable NA therapy were planned to receive GSK3965193 oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
Units
Counts
Participants
Secondary
Part 2B: AUC(0-inf) of GSK3965193 Following Single Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Not Posted
Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 48 h, and 72 h post-dose
Participants
Secondary
Part 2B: Cmax of GSK3965193 Following Single Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Not Posted
Pre-dose and 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, 48 h, and 72 h post-dose
Participants
Secondary
Part 3: AUC(0-tau) of GSK3965193 Following Repeat Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Not Posted
Pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 1; pre-dose on Day 4, Day 8, Day 11, Day 15, Day 22; pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 28
Participants
Secondary
Part 3: Cmax of GSK3965193 Following Repeat Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Not Posted
Pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 1; pre-dose on Day 4, Day 8, Day 11, Day 15, Day 22; pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 28
Participants
Secondary
Part 3: Tmax of GSK3965193 Following Repeat Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Not Posted
Pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 1; pre-dose on Day 4, Day 8, Day 11, Day 15, Day 22; pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 28
Participants
Secondary
Part 3: T1/2 of GSK3965193 Following Repeat Dose Administration
Blood samples were collected at indicated time points for PK analysis of GSK3965193. PK analysis was conducted using standard non-compartmental methods.
Not Posted
Pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 1; pre-dose on Day 4, Day 8, Day 11, Day 15, Day 22; pre-dose and 0.25 h, 0.5 h, 1 h, 2, h, 3 h, 4 h, 6 h, 8 h, and 12 h post-dose on Day 28
Participants
Secondary
Part 3: Number of Participants With Greater Than or Equal to [≥] 0.5 Times Log International Units Per Milliliters [IU/mL] Reduction From Baseline in Serum HBsAg Levels
Blood samples were collected from participants at indicated time points to assess HBsAg levels.
Not Posted
From Baseline (Day 1) up to 42 days
Participants
Secondary
Part 3: Number of Participants With TEAEs, STEAEs, and Treatment Withdrawals Due to TEAEs Among Participants Opting for Optional Bepirovirsen Treatment
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; abnormal pregnancy outcomes or other situations as per the medical or scientific judgment of the investigator.
Not Posted
From the start of study intervention up to 54 weeks
Participants
Secondary
Part 3: Number of Participants With Clinically Significant Hematology, Clinical Chemistry, and Urinalysis Parameters Among Participants Opting for Optional Bepirovirsen Treatment
Blood samples were planned to be collected to analyze clinical chemistry and hematology parameters: hemoglobin, leukocytes, lymphocytes/leukocytes, neutrophils/leukocytes, platelets, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cells, reticulocytes, ALT, albumin, alkaline phosphatase, AST, bilirubin, calcium corrected for albumin, creatinine, glucose, potassium, and sodium. Urine samples were planned to be analyzed using automated urinalysis or urine dipstick. Microscopic examination was performed if abnormal blood or protein was present in the urine sample. Number of participants with clinically significant clinical chemistry, hematology, and urinalysis parameters were reported. Clinical significance was determined by the investigator.
Not Posted
From Week 7 up to 54 weeks
Participants
Secondary
Part 3: Number of Participants With Clinically Significant Vital Signs Among Participants Opting for Optional Bepirovirsen Treatment
Vital signs were planned to include temperature and were planned to be measured with the participant in semi-supine position after 5 minutes rest. Clinical significance of vital signs was determined by the investigator.
Not Posted
From Week 7 up to 54 weeks
Participants
Secondary
Part 4: Number of Participants With HBsAg Loss
Blood samples were collected from participants at indicated time points to assess HBsAg levels. HBsAg loss is defined by two consecutive measurements of HBsAg below the LLOQ any time during the study (on-treatment and post-treatment).
Not Posted
Up to 48 weeks
Participants
Time Frame
All-cause mortality, non-serious TEAEs and STEAEs were collected up to 12 weeks for Part 1, 6 weeks for Part 2A, 9 weeks for Part 2B, and 6 weeks in Part 3.
Description
Safety Analysis Set included all participants who received at least one dose of study treatment. The study was terminated after completion of Part 3 as a strategic decision. Hence, no participants were enrolled in Part 4. STEAEs and non-serious TEAEs were coded to Medical Dictionary for Regulatory Activity (MedDRA) version (v) 25.1 for Part 1, v26.0 for Parts 2A and 2B, v28.1 for Part 3.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Part 1: Cohorts 1 and 2 - Placebo
Healthy participants from Part 1: Cohorts 1 and 2 received a single dose of placebo oral solution on Day 1 of either Treatment Periods 1, 2, 3, or 4.
0
16
0
16
2
16
EG001
Part 1: Cohort 1 - GSK3965193 Dose 1
Healthy participants received a single dose of GSK3965193 Dose 1 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 1 was the lowest dose in Cohort 1.
0
6
0
6
3
6
EG002
Part 1: Cohort 1 - GSK3965193 Dose 2
Healthy participants received a single dose of GSK3965193 Dose 2 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 2 was higher than Dose 1 but lower than Dose 3.
0
6
0
6
1
6
EG003
Part 1: Cohort 1 - GSK3965193 Dose 3
Healthy participants received a single dose of GSK3965193 Dose 3 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 3 was higher than Dose 2 but lower than Dose 4.
0
6
0
6
1
6
EG004
Part 1: Cohort 1 - GSK3965193 Dose 4
Healthy participants received a single dose of GSK3965193 Dose 4 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 4 was the highest dose in Cohort 1.
0
6
0
6
1
6
EG005
Part 1: Cohort 2 - GSK3965193 Dose 5
Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 5 was the lowest dose in Cohort 2 but was higher than Dose 4 of Cohort 1.
0
6
0
6
3
6
EG006
Part 1: Cohort 2 - GSK3965193 Dose 6
Healthy participants received a single dose of GSK3965193 Dose 6 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 6 was higher than Dose 5 but lower than Dose 7.
0
6
0
6
0
6
EG007
Part 1: Cohort 2 - GSK3965193 Dose 7
Healthy participants received a single dose of GSK3965193 Dose 7 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 7 was higher than Dose 6 but lower than Dose 8.
0
6
0
6
1
6
EG008
Part 1: Cohort 2 - GSK3965193 Dose 8
Healthy participants received a single dose of GSK3965193 Dose 8 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 8 was the highest dose in Cohort 2.
0
6
0
6
0
6
EG009
Part 2A: Placebo
Healthy participants received repeat doses of placebo oral solution twice daily (BID) for 14 days.
0
6
0
6
4
6
EG010
Part 2A: Cohort 5 - GSK3965193 Dose 9 BID
Healthy participants received repeat doses of GSK3965193 Dose 9 oral solution BID for 14 days. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
0
6
0
6
6
6
EG011
Part 2A: Cohort 3 - GSK3965193 Dose 5 BID
Healthy participants received repeat doses of GSK3965193 Dose 5 oral solution BID for 14 days. Dose 5 of GSK3965193 was higher than Dose 9 but lower than Dose 10.
0
7
0
7
4
7
EG012
Part 2A: Cohort 4 - GSK3965193 Dose 6 BID
Healthy participants received repeat doses of GSK3965193 Dose 6 oral solution BID for 14 days. Dose 6 of GSK3965193 was higher than Dose 10 but lower than Dose 7.
0
4
0
4
4
4
EG013
Part 2B: Cohort 6 - GSK3965193 Dose 10 Fasted
Healthy participants received GSK3965193 Dose 10 oral tablets under fasted condition in either Treatment Periods 1 or 2. Dose 10 of GSK3965193 was higher than Dose 5 but lower than Dose 6.
0
11
0
11
3
11
EG014
Part 2B: Cohort 6 - GSK3965193 Dose 10 Fed
Healthy participants received GSK3965193 Dose 10 oral tablets under fed condition in either Treatment Periods 1 or 2. Dose 10 of GSK3965193 was higher than Dose 5 but lower than Dose 6.
0
13
0
13
1
13
EG015
Part 3: Cohort 7 - Placebo
Participants living with chronic hepatitis B infection (PLWCHB) on stable nucleos(t)ide analog (NA) therapy received repeat doses of placebo oral tablets for 28 days. Participants who completed placebo monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen subcutaneous (SC) injection from Day 43.
0
4
0
4
2
4
EG016
Part 3: Cohort 7 - GSK3965193 Dose 9
PLWCHB on stable NA therapy received repeat doses of GSK3965193 Dose 9 oral tablets for 28 days. Participants who completed GSK3965193 monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen SC injection from Day 43. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
0
14
0
14
4
14
EG017
Part 4: Cohort 8 - Placebo + Bepirovirsen
PLWCHB on stable NA therapy were planned to receive placebo oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
0
0
0
0
0
0
EG018
Part 4: Cohort 8 - GSK3965193 + Bepirovirsen
PLWCHB on stable NA therapy were planned to receive GSK3965193 oral tablets plus bepirovirsen SC injection for 28 days. All participants were further planned to continue receiving bepirovirsen SC injection after 28 days.
0
0
0
0
0
0
Serious Adverse Events
Not provided
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Palpitations
Cardiac disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected6 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected6 at risk
EG0090 events0 affected6 at risk
EG0101 events1 affected6 at risk
EG0110 events0 affected7 at risk
EG0120 events0 affected4 at risk
EG0130 events0 affected11 at risk
EG0140 events0 affected13 at risk
EG0150 events0 affected4 at risk
EG0163 events1 affected14 at risk
EG0170 events0 affected0 at risk
EG0180 events0 affected0 at risk
Sinus tachycardia
Cardiac disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Ear discomfort
Ear and labyrinth disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Tinnitus
Ear and labyrinth disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Asthenia
General disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Catheter site bruise
General disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Catheter site haemorrhage
General disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0001 events1 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Catheter site pain
General disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Chills
General disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Fatigue
General disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Feeling abnormal
General disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Feeling hot
General disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hangover
General disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hunger
General disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
COVID-19
Infections and infestations
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Folliculitis
Infections and infestations
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Suspected COVID-19
Infections and infestations
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Arthropod bite
Injury, poisoning and procedural complications
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Ligament sprain
Injury, poisoning and procedural complications
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Lip injury
Injury, poisoning and procedural complications
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Post procedural complication
Injury, poisoning and procedural complications
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Balance disorder
Nervous system disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Brain fog
Nervous system disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dizziness
Nervous system disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Head discomfort
Nervous system disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Headache
Nervous system disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0001 events1 affected16 at risk
EG0012 events2 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Memory impairment
Nervous system disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Migraine
Nervous system disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Presyncope
Nervous system disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Sensory disturbance
Nervous system disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Somnolence
Nervous system disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Disorientation
Psychiatric disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Nervousness
Psychiatric disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Nightmare
Psychiatric disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Tension
Psychiatric disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dry throat
Respiratory, thoracic and mediastinal disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Sinus congestion
Respiratory, thoracic and mediastinal disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dermal cyst
Skin and subcutaneous tissue disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dermatitis contact
Skin and subcutaneous tissue disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Skin irritation
Skin and subcutaneous tissue disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Flushing
Vascular disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hypotension
Vascular disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Poor peripheral circulation
Vascular disorders
MedDRA25.1;26.0;28.1
Systematic Assessment
EG0000 events0 affected16 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single site data not precede the primary publication of the entire clinical trial.
Healthy participants received a single dose of GSK3965193 Dose 7 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 7 was higher than Dose 6 but lower than Dose 8.
OG008
Part 1: Cohort 2 - GSK3965193 Dose 8
Healthy participants received a single dose of GSK3965193 Dose 8 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 8 was the highest dose in Cohort 2.
6
OG0046
OG0056
OG0066
OG0076
OG0086
1
OG0041
OG0053
OG0060
OG0071
OG0080
Any STEAE
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0060
OG0070
OG0080
Treatment Withdrawals due to TEAEs
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0051
OG0060
OG0071
OG0080
Part 2A: Cohort 3 - GSK3965193 Dose 5 BID
Healthy participants received repeat doses of GSK3965193 Dose 5 oral solution BID for 14 days. Dose 5 of GSK3965193 was higher than Dose 9 but lower than Dose 10.
OG003
Part 2A: Cohort 4 - GSK3965193 Dose 6 BID
Healthy participants received repeat doses of GSK3965193 Dose 6 oral solution BID for 14 days. Dose 6 of GSK3965193 was higher than Dose 10 but lower than Dose 7.
Units
Counts
Participants
OG0006
OG0016
OG0027
OG0034
Title
Denominators
Categories
Any TEAE
Title
Measurements
OG0004
OG0016
OG0024
OG0034
Any STEAE
Title
Measurements
OG0000
OG0010
OG0020
OG003
Treatment Withdrawals due to TEAEs
Title
Measurements
OG0000
OG0011
OG0022
OG003
Healthy participants received GSK3965193 Dose 10 oral tablets under fed condition in either Treatment Periods 1 or 2. Dose 10 of GSK3965193 was higher than Dose 5 but lower than Dose 6.
Units
Counts
Participants
OG00011
OG00113
Title
Denominators
Categories
Any TEAE
Title
Measurements
OG0003
OG0011
Any STEAE
Title
Measurements
OG0000
OG0010
Treatment Withdrawals due to TEAEs
Title
Measurements
OG0000
OG0010
PLWCHB on stable NA therapy received repeat doses of GSK3965193 Dose 9 oral tablets for 28 days. Participants who completed GSK3965193 monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen SC injection from Day 43. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.
Units
Counts
Participants
OG0004
OG00114
Title
Denominators
Categories
Any TEAE
Title
Measurements
OG0002
OG0014
Any STEAE
Title
Measurements
OG0000
OG0010
Withdrawals due to TEAEs
Title
Measurements
OG0000
OG0011
Units
Counts
Participants
OG0000
OG0010
OG002
Part 1: Cohort 1 - GSK3965193 Dose 2
Healthy participants received a single dose of GSK3965193 Dose 2 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 2 was higher than Dose 1 but lower than Dose 3.
OG003
Part 1: Cohort 1 - GSK3965193 Dose 3
Healthy participants received a single dose of GSK3965193 Dose 3 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 3 was higher than Dose 2 but lower than Dose 4.
OG004
Part 1: Cohort 1 - GSK3965193 Dose 4
Healthy participants received a single dose of GSK3965193 Dose 4 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 4 was the highest dose in Cohort 1.
OG005
Part 1: Cohort 2 - GSK3965193 Dose 5
Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 5 was the lowest dose in Cohort 2 but was higher than Dose 4 of Cohort 1.
OG006
Part 1: Cohort 2 - GSK3965193 Dose 6
Healthy participants received a single dose of GSK3965193 Dose 6 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 6 was higher than Dose 5 but lower than Dose 7.
OG007
Part 1: Cohort 2 - GSK3965193 Dose 7
Healthy participants received a single dose of GSK3965193 Dose 7 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 7 was higher than Dose 6 but lower than Dose 8.
OG008
Part 1: Cohort 2 - GSK3965193 Dose 8
Healthy participants received a single dose of GSK3965193 Dose 8 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 8 was the highest dose in Cohort 2.
Units
Counts
Participants
OG00016
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
OG0076
OG0086
Title
Denominators
Categories
Hematology
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0060
OG0070
OG0080
Clinical Chemistry
Title
Measurements
OG0000
OG0010
OG0020
OG003
Part 2A: Cohort 3 - GSK3965193 Dose 5 BID
Healthy participants received repeat doses of GSK3965193 Dose 5 oral solution BID for 14 days. Dose 5 of GSK3965193 was higher than Dose 9 but lower than Dose 10.
OG003
Part 2A: Cohort 4 - GSK3965193 Dose 6 BID
Healthy participants received repeat doses of GSK3965193 Dose 6 oral solution BID for 14 days. Dose 6 of GSK3965193 was higher than Dose 10 but lower than Dose 7.
Units
Counts
Participants
OG0006
OG0016
OG0027
OG0034
Title
Denominators
Categories
Hematology
Title
Measurements
OG0000
OG0010
OG0020
OG0030
Clinical Chemistry
Title
Measurements
OG0000
OG0010
OG0020
OG003
Urinalysis
Title
Measurements
OG0000
OG0010
OG0020
OG003
Units
Counts
Participants
OG00011
OG00113
Title
Denominators
Categories
Hematology
Title
Measurements
OG0000
OG0010
Clinical Chemistry
Title
Measurements
OG0000
OG0010
Urinalysis
Title
Measurements
OG0000
OG0010
Units
Counts
Participants
OG0004
OG00114
Title
Denominators
Categories
Hematology
Title
Measurements
OG0000
OG0010
Clinical Chemistry
Title
Measurements
OG0001
OG0010
Units
Counts
Participants
OG0004
OG00114
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
Units
Counts
Participants
OG0000
OG0010
OG003
Part 1: Cohort 1 - GSK3965193 Dose 3
Healthy participants received a single dose of GSK3965193 Dose 3 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 3 was higher than Dose 2 but lower than Dose 4.
OG004
Part 1: Cohort 1 - GSK3965193 Dose 4
Healthy participants received a single dose of GSK3965193 Dose 4 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 4 was the highest dose in Cohort 1.
OG005
Part 1: Cohort 2 - GSK3965193 Dose 5
Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 5 was the lowest dose in Cohort 2 but was higher than Dose 4 of Cohort 1.
OG006
Part 1: Cohort 2 - GSK3965193 Dose 6
Healthy participants received a single dose of GSK3965193 Dose 6 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 6 was higher than Dose 5 but lower than Dose 7.
OG007
Part 1: Cohort 2 - GSK3965193 Dose 7
Healthy participants received a single dose of GSK3965193 Dose 7 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 7 was higher than Dose 6 but lower than Dose 8.
OG008
Part 1: Cohort 2 - GSK3965193 Dose 8
Healthy participants received a single dose of GSK3965193 Dose 8 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 8 was the highest dose in Cohort 2.
Units
Counts
Participants
OG00016
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
OG0076
OG0086
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0060
OG0070
OG0080
Healthy participants received repeat doses of GSK3965193 Dose 6 oral solution BID for 14 days. Dose 6 of GSK3965193 was higher than Dose 10 but lower than Dose 7.
Units
Counts
Participants
OG0006
OG0016
OG0027
OG0034
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0021
OG0030
OG00011
OG00113
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
Units
Counts
Participants
OG0004
OG00114
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0000
OG0010
OG003
Part 1: Cohort 1 - GSK3965193 Dose 3
Healthy participants received a single dose of GSK3965193 Dose 3 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 3 was higher than Dose 2 but lower than Dose 4.
OG004
Part 1: Cohort 1 - GSK3965193 Dose 4
Healthy participants received a single dose of GSK3965193 Dose 4 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 4 was the highest dose in Cohort 1.
OG005
Part 1: Cohort 2 - GSK3965193 Dose 5
Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 5 was the lowest dose in Cohort 2 but was higher than Dose 4 of Cohort 1.
OG006
Part 1: Cohort 2 - GSK3965193 Dose 6
Healthy participants received a single dose of GSK3965193 Dose 6 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 6 was higher than Dose 5 but lower than Dose 7.
OG007
Part 1: Cohort 2 - GSK3965193 Dose 7
Healthy participants received a single dose of GSK3965193 Dose 7 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 7 was higher than Dose 6 but lower than Dose 8.
OG008
Part 1: Cohort 2 - GSK3965193 Dose 8
Healthy participants received a single dose of GSK3965193 Dose 8 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 8 was the highest dose in Cohort 2.
Units
Counts
Participants
OG00016
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
OG0076
OG0086
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
OG0060
OG0070
OG0080
Part 2A: Cohort 4 - GSK3965193 Dose 6 BID
Healthy participants received repeat doses of GSK3965193 Dose 6 oral solution BID for 14 days. Dose 6 of GSK3965193 was higher than Dose 10 but lower than Dose 7.
Units
Counts
Participants
OG0006
OG0016
OG0027
OG0034
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
Units
Counts
Participants
OG0004
OG00114
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0000
OG0010
Healthy participants received repeat doses of GSK3965193 Dose 5 oral solution BID for 14 days. Dose 5 of GSK3965193 was higher than Dose 9 but lower than Dose 10.
OG003
Part 2A: Cohort 4 - GSK3965193 Dose 6 BID
Healthy participants received repeat doses of GSK3965193 Dose 6 oral solution BID for 14 days. Dose 6 of GSK3965193 was higher than Dose 10 but lower than Dose 7.
Units
Counts
Participants
OG0005
OG0016
OG0026
OG0034
Title
Denominators
Categories
25% decrease in nerve conduction velocity
Title
Measurements
OG0000
OG0010
OG0020
OG0030
50% decrease in nerve conduction amplitude
Title
Measurements
OG0000
OG0010
OG0021
OG003
OG002
Part 2A: Cohort 3 - GSK3965193 Dose 5 BID
Healthy participants received repeat doses of GSK3965193 Dose 5 oral solution BID for 14 days. Dose 5 of GSK3965193 was higher than Dose 9 but lower than Dose 10.
OG003
Part 2A: Cohort 4 - GSK3965193 Dose 6 BID
Healthy participants received repeat doses of GSK3965193 Dose 6 oral solution BID for 14 days. Dose 6 of GSK3965193 was higher than Dose 10 but lower than Dose 7.
Units
Counts
Participants
OG0004
OG0013
OG0025
OG0030
Title
Denominators
Categories
25% decrease in nerve conduction velocity
Title
Measurements
OG0000
OG0010
OG0020
50% decrease in nerve conduction amplitude
Title
Measurements
OG0000
OG0010
OG0020
OG002
Part 2A: Cohort 3 - GSK3965193 Dose 5 BID
Healthy participants received repeat doses of GSK3965193 Dose 5 oral solution BID for 14 days. Dose 5 of GSK3965193 was higher than Dose 9 but lower than Dose 10.
OG003
Part 2A: Cohort 4 - GSK3965193 Dose 6 BID
Healthy participants received repeat doses of GSK3965193 Dose 6 oral solution BID for 14 days. Dose 6 of GSK3965193 was higher than Dose 10 but lower than Dose 7.
Units
Counts
Participants
OG0004
OG0012
OG0025
OG0030
Title
Denominators
Categories
25% decrease in nerve conduction velocity
Title
Measurements
OG0000
OG0010
OG0020
50% decrease in nerve conduction amplitude
Title
Measurements
OG0000
OG0010
OG0020
Units
Counts
Participants
OG0004
OG00114
Title
Denominators
Categories
25% decrease in nerve conduction velocity
Title
Measurements
OG0000
OG0010
50% decrease in nerve conduction amplitude
Title
Measurements
OG0000
OG0010
Units
Counts
Participants
OG0004
OG00113
Title
Denominators
Categories
25% decrease in nerve conduction velocity
Title
Measurements
OG0000
OG0010
50% decrease in nerve conduction amplitude
Title
Measurements
OG0000
OG0010
OG0000
OG0010
Healthy participants received a single dose of GSK3965193 Dose 3 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 3 was higher than Dose 2 but lower than Dose 4.
OG003
Part 1: Cohort 1 - GSK3965193 Dose 4
Healthy participants received a single dose of GSK3965193 Dose 4 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 4 was the highest dose in Cohort 1.
OG004
Part 1: Cohort 2 - GSK3965193 Dose 5
Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 5 was the lowest dose in Cohort 2 but was higher than Dose 4 of Cohort 1.
OG005
Part 1: Cohort 2 - GSK3965193 Dose 6
Healthy participants received a single dose of GSK3965193 Dose 6 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 6 was higher than Dose 5 but lower than Dose 7.
OG006
Part 1: Cohort 2 - GSK3965193 Dose 7
Healthy participants received a single dose of GSK3965193 Dose 7 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 7 was higher than Dose 6 but lower than Dose 8.
OG007
Part 1: Cohort 2 - GSK3965193 Dose 8
Healthy participants received a single dose of GSK3965193 Dose 8 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 8 was the highest dose in Cohort 2.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
OG0076
Title
Denominators
Categories
Title
Measurements
OG0001.95± 20.31
OG0017.46± 20.21
OG00214.50± 15.24
OG00347.35± 15.72
OG004147.02± 26.27
OG005412.52± 23.01
OG0061675.39± 29.13
OG0073207.43± 34.82
OG002
Part 2A: Cohort 4 - GSK3965193 Dose 6 BID
Healthy participants received repeat doses of GSK3965193 Dose 6 oral solution BID for 14 days. Dose 6 of GSK3965193 was higher than Dose 10 but lower than Dose 7.
Units
Counts
Participants
OG0006
OG0017
OG0024
Title
Denominators
Categories
Day 1
ParticipantsOG0006
ParticipantsOG0017
ParticipantsOG0024
Title
Measurements
OG00054.16± 18.53
OG001123.78± 14.85
OG002296.23± 15.40
Day 14
ParticipantsOG0003
ParticipantsOG0015
ParticipantsOG0020
Title
Measurements
OG000
OG003
Part 1: Cohort 1 - GSK3965193 Dose 4
Healthy participants received a single dose of GSK3965193 Dose 4 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 4 was the highest dose in Cohort 1.
OG004
Part 1: Cohort 2 - GSK3965193 Dose 5
Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 5 was the lowest dose in Cohort 2 but was higher than Dose 4 of Cohort 1.
OG005
Part 1: Cohort 2 - GSK3965193 Dose 6
Healthy participants received a single dose of GSK3965193 Dose 6 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 6 was higher than Dose 5 but lower than Dose 7.
OG006
Part 1: Cohort 2 - GSK3965193 Dose 7
Healthy participants received a single dose of GSK3965193 Dose 7 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 7 was higher than Dose 6 but lower than Dose 8.
OG007
Part 1: Cohort 2 - GSK3965193 Dose 8
Healthy participants received a single dose of GSK3965193 Dose 8 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 8 was the highest dose in Cohort 2.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
OG0076
Title
Denominators
Categories
Title
Measurements
OG0000.26± 14.75
OG0011.05± 22.02
OG0022.24± 16.85
OG0038.43± 14.05
OG00425.08± 11.65
OG00581.00± 13.38
OG006247.21± 21.43
OG007504.23± 24.24
OG002
Part 2A: Cohort 4 - GSK3965193 Dose 6 BID
Healthy participants received repeat doses of GSK3965193 Dose 6 oral solution BID for 14 days. Dose 6 of GSK3965193 was higher than Dose 10 but lower than Dose 7.
Units
Counts
Participants
OG0006
OG0017
OG0024
Title
Denominators
Categories
Day 1
ParticipantsOG0006
ParticipantsOG0017
ParticipantsOG0024
Title
Measurements
OG00010.38± 29.16
OG00122.93± 18.19
OG00272.56± 22.24
Day 14
ParticipantsOG0003
ParticipantsOG0015
ParticipantsOG0020
Title
Measurements
OG000
OG003
Part 1: Cohort 1 - GSK3965193 Dose 4
Healthy participants received a single dose of GSK3965193 Dose 4 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 4 was the highest dose in Cohort 1.
OG004
Part 1: Cohort 2 - GSK3965193 Dose 5
Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 5 was the lowest dose in Cohort 2 but was higher than Dose 4 of Cohort 1.
OG005
Part 1: Cohort 2 - GSK3965193 Dose 6
Healthy participants received a single dose of GSK3965193 Dose 6 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 6 was higher than Dose 5 but lower than Dose 7.
OG006
Part 1: Cohort 2 - GSK3965193 Dose 7
Healthy participants received a single dose of GSK3965193 Dose 7 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 7 was higher than Dose 6 but lower than Dose 8.
OG007
Part 1: Cohort 2 - GSK3965193 Dose 8
Healthy participants received a single dose of GSK3965193 Dose 8 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 8 was the highest dose in Cohort 2.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
OG0076
Title
Denominators
Categories
Title
Measurements
OG0000.50(0.5 to 2.0)
OG0010.51(0.3 to 2.0)
OG0020.38(0.3 to 1.0)
OG0030.38(0.3 to 0.5)
OG0040.50(0.3 to 0.5)
OG0050.38(0.3 to 0.5)
OG0060.50(0.5 to 1.0)
OG0070.50(0.3 to 1.0)
OG002
Part 2A: Cohort 4 - GSK3965193 Dose 6 BID
Healthy participants received repeat doses of GSK3965193 Dose 6 oral solution BID for 14 days. Dose 6 of GSK3965193 was higher than Dose 10 but lower than Dose 7.
Units
Counts
Participants
OG0006
OG0017
OG0024
Title
Denominators
Categories
Day 1
ParticipantsOG0006
ParticipantsOG0017
ParticipantsOG0024
Title
Measurements
OG0000.38(0.3 to 1.0)
OG0010.50(0.3 to 2.0)
OG0020.38(0.3 to 0.5)
Day 14
ParticipantsOG0003
ParticipantsOG0015
ParticipantsOG0020
Title
Measurements
OG000
OG003
Part 1: Cohort 1 - GSK3965193 Dose 4
Healthy participants received a single dose of GSK3965193 Dose 4 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 4 was the highest dose in Cohort 1.
OG004
Part 1: Cohort 2 - GSK3965193 Dose 5
Healthy participants received a single dose of GSK3965193 Dose 5 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 5 was the lowest dose in Cohort 2 but was higher than Dose 4 of Cohort 1.
OG005
Part 1: Cohort 2 - GSK3965193 Dose 6
Healthy participants received a single dose of GSK3965193 Dose 6 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 6 was higher than Dose 5 but lower than Dose 7.
OG006
Part 1: Cohort 2 - GSK3965193 Dose 7
Healthy participants received a single dose of GSK3965193 Dose 7 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 7 was higher than Dose 6 but lower than Dose 8.
OG007
Part 1: Cohort 2 - GSK3965193 Dose 8
Healthy participants received a single dose of GSK3965193 Dose 8 oral solution on Day 1 in either Treatment Periods 1, 2, 3, or 4. Dose 8 was the highest dose in Cohort 2.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG0066
OG0076
Title
Denominators
Categories
Title
Measurements
OG0007.40± 1.732
OG0017.17± 1.568
OG0027.62± 1.061
OG0037.92± 0.814
OG0048.26± 1.415
OG0057.57± 0.443
OG0067.63± 0.561
OG0077.57± 1.054
OG002
Part 2A: Cohort 4 - GSK3965193 Dose 6 BID
Healthy participants received repeat doses of GSK3965193 Dose 6 oral solution BID for 14 days. Dose 6 of GSK3965193 was higher than Dose 10 but lower than Dose 7.
Units
Counts
Participants
OG0006
OG0017
OG0024
Title
Denominators
Categories
Day 1
ParticipantsOG0006
ParticipantsOG0017
ParticipantsOG0024
Title
Measurements
OG0005.53± 0.871
OG0015.15± 1.199
OG0024.26± 0.966
Day 14
ParticipantsOG0003
ParticipantsOG0015
ParticipantsOG0020
Title
Measurements
OG000
OG001
Part 3: Cohort 7 - GSK3965193 Dose 9
PLWCHB on stable NA therapy received repeat doses of GSK3965193 Dose 9 oral tablets for 28 days. Participants who completed GSK3965193 monotherapy were given the option to receive subsequent treatment of optional open label bepirovirsen SC injection from Day 43. Dose 9 of GSK3965193 was higher than Dose 4 but lower than Dose 5.