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The study was terminated early (following completion of SAD Cohort 3; 80 mg) based on PK/PD modelling which demonstrated the medicine's intended target profile was not achievable.
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This is a phase 1, 2-part, double-blind (sponsor-unblinded), randomized, placebo-controlled, FTIH study, that includes both single-ascending and multiple-ascending dose phase to assess the safety, tolerability, and pharmacokinetic (PK)/pharmacodynamic (PD) attributes of GSK3732394 in healthy subjects. The data gathered in this study will further enable clinical development of GSK3732394 in HIV-infected subjects. Approximately 72 healthy subjects will be randomized in the FTIH study. Part 1 will be the single ascending dose (SAD) phase and Part 2 will be the multiple ascending dose (MAD) phase. Each subject in the SAD cohort will receive a single dose of blinded GSK3732394 or blinded placebo (PBO) in 6:2 ratio. Part 1 will consist of five ascending single-dose cohorts with an additional expansion cohort included as needed. Part 2 will consist of up to three ascending repeat-dose cohorts (MAD Cohorts 1, 2, and 3), randomized to four weekly doses of blinded GSK3732394 or blinded PBO in 6:2 ratio to be administered on Days 1, 8, 15, and 22.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1,Cohort 1:Subjects receiving blinded GSK3732394 10mg/PBO | Experimental | GSK3732394 10 milligram (mg) or PBO will be administered by subcutaneous (SC) injection to the subjects. |
|
| Part 1,Cohort 2:Subjects receiving blinded GSK3732394 40mg/PBO | Experimental | GSK3732394 40 mg or PBO will be administered by SC injection to the subjects. This is projected dose, dose will be based on PK/PD results from preceding dosing cohorts. |
|
| Part1,Cohort 3:Subjects receiving blinded GSK3732394 130mg/PBO | Experimental | GSK3732394 130 mg or PBO will be administered by SC injection to the subjects. This is a projected dose. The dose administered in Part 1, Cohort 3 will be based on PK/PD results from preceding dosing cohorts. |
|
| Part1,Cohort 4:Subjects receiving blinded GSK3732394 350mg/PBO | Experimental | GSK3732394 350 mg or PBO will be administered by SC injection to the subjects. This is a projected dose. The dose administered in Part 1, Cohort 4 will be based on PK/PD results from preceding dosing cohorts. |
|
| Part1,Cohort5: Subjects receiving blinded GSK3732394 600mg/PBO |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK3732394 | Drug | It is composed of an anti-CD4 adnectin, an anti-N17 adnectin, and a peptide inhibitor. This will be provided as a solution for injection in 1 (milliliter) mL glass vials with the unit dose strength of 100 mg/mL |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Number of Participants With Non-serious Adverse Event (SAEs) and SAEs | 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. A SAE is defined as any untoward medical occurrence that, at any dose: results in death and is life-threatening which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly, or any other situation that require medical or scientific judgement. Number of participants with common more than or equal to (>=)5 percent (%) non-serious AEs and SAEs are presented. | Up to Day 28 |
| Part 2: Number of Participants With Non-SAEs and SAEs | 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. A SAE is defined as any untoward medical occurrence that, at any dose: results in death and is life-threatening which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly, or any other situation that require medical or scientific judgement. All AEs were planned to be collected from the start of treatment until the follow-up visit. | Up to Day 49 |
| Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Blood samples were collected for the analysis of following clinical chemistry parameters: Glucose, alkaline phosphatase, alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), direct bilirubin, total bilirubin, calcium, creatinine, potassium, lipase and sodium. The clinical chemistry abnormalities were graded using the Division of Acquired immunodeficiency syndrome (DAIDS) criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severe condition. Baseline is defined as the latest pre-dose assessment. Number of participants with clinical chemistry parameters by maximum grade increase post-Baseline is presented. |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Area Under the Plasma Concentration Time Curve From Zero to t (AUC[0-t]) Following Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | ViiV Healthcare | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Baltimore | Maryland | 21225 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36191080 | Derived | Krystal M, Chabria S, Austin D, Wolstenholme A, Wensel D, Lataillade M, Abberbock J, Baker M, Ackerman P. A Phase 1 randomized study of GSK3732394, an investigational long-acting biologic treatment regimen for HIV-1 infection. Antivir Ther. 2022 Oct;27(5):13596535221131164. doi: 10.1177/13596535221131164. |
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IPD for this study will be made available via the Clinical Study Data Request site.
IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
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.
A total of 24 healthy participants were enrolled in the study across the United States. This study was terminated due to non-safety reasons; hence, Part 1 (Cohorts 4 to 6) and Part 2 were not conducted.
This was to have been a 2 part study, conducted to investigate single ascending doses (SAD) in Part 1 and repeated once-weekly multiple ascending doses (MAD) in Part 2. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1- Cohort 1: GSK3732394 10 mg | Healthy adult participants were administered a single subcutaneous (SC) dose of blinded GSK3732394 10 milligrams (mg) on Day 1. |
| FG001 | Part 1- Cohort 2: GSK3732394 20 mg | Healthy adult participants were administered a single SC dose of blinded GSK3732394 20 mg on Day 1. |
| FG002 | Part 1- Cohort 3: GSK3732394 80 mg | Healthy adult participants were administered a single SC dose of blinded GSK3732394 80 mg on Day 1. |
| FG003 | Part 1- Placebo | Healthy adult participants were administered a single SC dose of blinded GSK3732394 matching placebo on Day 1 in cohorts 1, 2, and 3. |
| FG004 | Part 1- Cohort 4: GSK3732394 | Healthy adult participants were planned to be administered a single SC dose of blinded GSK3732394 |
| FG005 | Part 1- Cohort 5: GSK3732394 | Healthy adult participants were planned to be administered a single SC dose of blinded GSK3732394. |
| FG006 | Part 1- Cohort 6: GSK3732394 | Healthy adult participants were planned to be administered a single SC dose of blinded GSK3732394. |
| FG007 | Part 2- Cohort 1: GSK3732394 | Healthy adult participants were planned to be administered a weekly dose of SC GSK3732394 on Days 1, 8, 15 and 22. |
| FG008 | Part 2- Cohort 2: GSK3732394 | Healthy adult participants were planned to be administered a weekly dose of SC GSK3732394 on Days 1, 8, 15 and 22 |
| FG009 | Part 2- Cohort 3: GSK3732394 | Healthy adult participants were planned to be administered a weekly dose of SC GSK3732394 on Days 1, 8, 15 and 22. |
| FG010 | Part 2: Placebo | Healthy adult participants were planned to be administered a weekly dose of SC GSK3732394 matching placebo on Days 1, 8, 15 and 22 in cohorts 1, 2 and 3. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 (Up to Day 28) |
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| ||||||||||||||||||
| Part 2 (Up to Day 49) |
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Only data for Part 1 is presented as study was terminated during Part 1; Part 2 was not initiated.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1- Cohort 1: GSK3732394 10 mg | Healthy adult participants were administered a single subcutaneous (SC) dose of blinded GSK3732394 10 milligrams (mg) on Day 1. |
| BG001 | Part 1- Cohort 2: GSK3732394 20 mg |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Only data for Part 1 is presented as study was terminated during Part 1; Part 2 was not initiated. |
| 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 Non-serious Adverse Event (SAEs) and SAEs | 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. A SAE is defined as any untoward medical occurrence that, at any dose: results in death and is life-threatening which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly, or any other situation that require medical or scientific judgement. Number of participants with common more than or equal to (>=)5 percent (%) non-serious AEs and SAEs are presented. | Safety Population consisted of all participants who received at least 1 dose of study treatment. Participants will be analyzed according to the treatment they actually received. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Count of Participants | Participants | Up to Day 28 |
Non-SAEs and SAEs were collected from start of study intervention (Day 1) up to Day 28.
Safety Population consisted of all participants who received at least 1 dose of study treatment. Data is presented for Part 1- Cohorts 1 to 3. Non-SAEs and SAEs were not collected for Part 1 (Cohorts 4 to 6) and Part 2 as the study was terminated after Part 1-Cohort 3.
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| 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- Cohort 1: GSK3732394 10 mg | Healthy adult participants were administered a single subcutaneous (SC) dose of blinded GSK3732394 10 milligrams (mg) on Day 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site hypersensitivity | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | ViiV Healthcare | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 12, 2019 | Mar 5, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 4, 2020 | Mar 5, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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In Part 1 of the study each of the subjects in the SAD cohorts (SAD Cohorts 1-5; SAD Cohort 6 is a possible expansion cohort that will be added as needed) will receive a single dose of blinded GSK3732394 or blinded PBO (GSK3732394: PBO = 6:2), per their randomization assignment. Part 2 will consist of up to three ascending repeat-dose cohorts (MAD Cohorts 1, 2, and 3), each with 8 subjects (blinded GSK3732394: blinded PBO = 6:2) will receive four weekly doses of GSK3732394 or PBO on Days 1, 8, 15, and 22.
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This is double-blind (sponsor-unblinded) study with subjects and the site staff blinded, except for an unblinded pharmacist at the site who will prepare the blinded drug product. The blind may be broken if, in the opinion of the investigator, it is in the subject's best interest for the investigator to know the study treatment assignment.
GSK3732394 600 mg or PBO will be administered by SC injection to the subjects. This is a projected dose. The dose administered in Part 1, Cohort 5 will be based on PK/PD results from preceding dosing cohorts. |
|
| Part1,Cohort6: Subjects receiving blinded GSK3732394 800mg/PBO | Experimental | GSK3732394 800 mg or PBO will be administered by SC injection to the subjects. This is a projected dose and will be given if necessary. The dose administered in Part 1, Cohort 6 (if necessary) will be based on PK/PD results from preceding dosing cohorts. |
|
| Part2,Cohort1: Subjects receiving blinded GSK3732394 130mg/PBO | Experimental | GSK3732394 130 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. This is a projected dose. The dose administered in Part 2, Cohort 1 will be based on PK/PD results from preceding dosing cohorts. |
|
| Part2,Cohort2: Subjects receiving blinded GSK3732394 400mg/PBO | Experimental | GSK3732394 400 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. This is a projected dose. The administered dose in Part 2, Cohort 2 will be based on PK/PD results from preceding dosing cohorts. |
|
| Part2,Cohort3: Subjects receiving blinded GSK3732394 600mg/PBO | Experimental | GSK3732394 600 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. This is a projected dose. The administered dose in Part 2, Cohort 3 will be based on PK/PD results from preceding dosing cohorts and will not exceed the maximum exposure observed in SAD (Part 1). |
|
| Placebo | Drug | Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride. |
|
| Up to Day 28 |
| Part 2: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Blood samples were planned to be collected for the analysis of the following clinical chemistry parameters: Glucose, alkaline phosphatase, ALT, amylase, AST, direct and total bilirubin, calcium, creatinine, potassium, lipase and sodium. Baseline is defined as the latest pre-dose assessment. | Up to Day 49 |
| Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Blood samples were collected for the analysis of following hematology parameters: Cluster of differentiation (CD) 4 cells, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. The hematology abnormalities were graded using the DAIDS criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severe condition. Baseline is defined as the latest pre-dose assessment. Number of participants with hematology parameters by maximum grade increase post-Baseline is presented. | Up to Day 28 |
| Part 2: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Blood samples were planned to be collected for the analysis of the following hematology parameters: CD4 cells, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. Baseline is defined as the latest pre-dose assessment. | Up to Day 49 |
| Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Urine samples were collected for the analysis of urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. The urinalysis abnormalities were graded using the DAIDS criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Baseline is defined as the latest pre-dose assessment. Number of participants with urinalysis parameters by any increase in discrete or character values post Baseline is presented. | Up to Day 28 |
| Part 2: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Urine samples were planned to be collected for the analysis of urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. Baseline is defined as the latest pre-dose assessment. | Up to Day 49 |
| Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline | Pulse rate was measured in a semi-supine position after 5 minutes of rest. Participants are counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose value category are unchanged (e.g., High to High), or whose value became within range, are recorded in the "To within Range or No Change" category. Participants with missing Baseline value are assumed to have within range value. Participants were counted twice if the participant had both values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment. Number of participants with pulse rate change to low or to high and no change post Baseline is presented. | Up to Day 28 |
| Part 2: Number of Participants With Worst Case Pulse Rate Post Baseline | Pulse rate was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment. | Up to Day 49 |
| Part 1: Change From Baseline in Body Temperature | Body temperature was measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. | Baseline and at Day 1 (1, 2, 4, 8, 12 hours), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
| Part 2: Change From Baseline in Body Temperature | Body temperature was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. | Baseline and Up to Day 49 |
| Part 1: Change From Baseline in Respiratory Rate | Respiratory rate was measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. | Baseline and at Day 1 (1, 2, 4, 8, 12 hours), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
| Part 2: Change From Baseline in Respiratory Rate | Respiratory rate was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. | Baseline and Up to Day 49 |
| Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | SBP and DBP was measured in a semi-supine position after 5 minutes of rest. Participants are counted in the worst case category that their value changes to low, within range or no change, or high), unless there is no change in their category. Participants whose value category are unchanged (e.g., High to High), or whose value became within range, are recorded in the "To within Range or No Change" category. Participants with missing Baseline value are assumed to have within range value. Participants were counted twice if the participant had both values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment. Number of participants with SBP and DBP change to low and to high and no change post Baseline is presented. | Up to Day 28 |
| Part 2: Number of Participants With Worst Case SBP and DBP Post Baseline | SBP and DBP was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment. | Up to Day 49 |
| Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of 5 minutes. Twelve lead ECGs were obtained by using an automated ECG machine. Number of participants with clinical significant abnormal ECG findings are presented. | Pre-dose, 4, 12 hours on Day 1, 24 hours on Day 2, Days 8, 14, 17 and 28 |
| Part 2: Number of Participants With Clinical Significant Abnormal ECG Findings | 12-lead ECG recordings was planned to be measured. | Up to Day 49 |
| Part 2: AUC(0-t) After Repeat Dosing of GSK3732394 in First Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7 |
| Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) Following Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
| Part 2: AUC(0-infinity) After Repeat Dosing of GSK3732394 in First Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7 |
| Part 1: Maximum Observed Concentration (Cmax) Following Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
| Part 2: Cmax After Repeat Dosing of GSK3732394 in First Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7 |
| Part 2: Cmax After Repeat Dosing of GSK3732394 in Last Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28 |
| Part 1: Time of Occurrence of Cmax (Tmax) After Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were calculated using standard non-compartmental analysis. | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
| Part 2: Tmax After Repeat Dosing of GSK3732394 in First Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7 |
| Part 2: Tmax After Repeat Dosing of GSK3732394 in Last Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28 |
| Part 1: Lag Time Before Observation of Drug Concentrations (Tlag) After Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were calculated using standard non-compartmental analysis. | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
| Part 2: Tlag After Repeat Dosing of GSK3732394 in First Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7 |
| Part 1: Last Observable Concentration (Clast) After Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
| Part 1: Time of Last Observable Concentration (Tlast) After Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
| Part 1: Apparent Terminal Phase Half-life (t1/2) After Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
| Part 2: T1/2 After Repeat Dosing of GSK3732394 in Last Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28 |
| Part 1: Apparent Clearance (CL/F) After Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
| Part 2: CL/F After Repeat Dosing of GSK3732394 in Last Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28 |
| Part 2: Area Under the Concentration Time Curve at Steady State Within the Dosing Interval (AUC[0-tau]) After Repeat Dosing of GSK3732394 in Last Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28 |
| Part 2: Trough Concentration (Ctrough) After Repeat Dosing of GSK3732394 in Last Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28 |
| Part 2: Accumulation Ratio Using AUC(0-tau) (RAUC[0-tau]) After Repeat Dosing of GSK3732394 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. RAUC(0-tau) was planned to be calculated as the ratio of AUC(0-tau) on week 4 to AUC(0-tau) on week 1 . | Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28 |
| Part 2: Accumulation Ratio Using Cmax (RCmax) After Repeat Dosing of GSK3732394 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. RCmax was planned to be calculated as the ratio of Cmax on Week 4 to Cmax on Week 1. | Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28 |
| Part 2: Accumulation Ratio Using Ctrough (RCtrough) After Repeat Dosing of GSK3732394 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. RCtrough was planned to be calculated as the ratio of Ctrough on Week 4 to Ctrough on Week 1. | Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28 |
| Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for Pharmacodynamic (PD) analysis of CD4 receptors occupied by GSK3732394 on CD4+ T cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. | Baseline, Day 1 (0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
| Part 2: Change From Baseline in Percent of CD4 RO After Multiple Dose Administration of GSK3732394 | Blood samples were planned to be collected at indicated time points for PD analysis of CD4 receptors occupied by GSK3732394 on CD4+ T cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. | Baseline and up to Day 49 |
| Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for analysis of CD3+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. | Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28 |
| Part 2: Change From Baseline in CD3+ Cells Following Multiple Dose Administration of GSK3732394 | Blood samples were planned to be collected at indicated time points for analysis of CD3+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. | Baseline and up to Day 49 |
| Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for analysis of CD4+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. | Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28 |
| Part 2: Change From Baseline in CD4+ Cells Following Multiple Dose Administration of GSK3732394 | Blood samples were planned to be collected at indicated time points for analysis of CD4+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. | Baseline and up to Day 49 |
| Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for analysis of CD8+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. | Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28 |
| Part 2: Change From Baseline in CD8+ Cells Following Multiple Dose Administration of GSK3732394 | Blood samples were planned to be collected at indicated time points for analysis of CD8+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. | Baseline and up to Day 49 |
| Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for analysis of CD4+ cell MFI. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. | Baseline, Day 1 (0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
| Part 2: Change From Baseline in CD4+ Cell MFI Following Multiple Dose Administration of GSK3732394 | Blood samples were planned to be collected at indicated time points for analysis of CD4+ cell MFI. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. | Baseline and up to Day 49 |
| Part 1: Number of Participants With Anti-GSK3732394 Antibodies on Day 28 | Serum samples were collected to analyze antibodies against GSK3732394. The presence of anti-GSK3732394 antibodies was determined in serum samples using a validated bioanalytical method, which included a screening assay, confirmation assay and titer analysis. Positive samples were further characterized with additional assays to determine the specificity of the anti-GSK3732394 antibodies. Number of participants with presence of anti-GSK3732394 antibodies are presented. | Day 28 |
| Part 2: Number of Participants With Anti-GSK3732394 Antibodies | Serum samples were planned to be collected to analyze antibodies against GSK3732394. | Up to Day 49 |
| Part 1: Titer of Anti-drug Antibodies (ADAs) Against GSK3732394 on Day 28 | Serum samples were collected to analyze the titers of antibodies against GSK3732394. The presence of anti-GSK3732394 antibodies was determined in serum samples using a validated bioanalytical method, which included a screening assay, confirmation assay and titer analysis. Positive samples were further characterized with additional assays to determine the specificity of the anti-GSK3732394 antibodies. Positive samples were titrated to obtain the titers of antibodies. | Day 28 |
| Part 2: Titer of ADAs Against GSK3732394 | Serum samples were planned to be collected to analyze the titers of antibodies against GSK3732394. | Up to Day 49 |
| COMPLETED |
|
| NOT COMPLETED |
|
Healthy adult participants were administered a single SC dose of blinded GSK3732394 20 mg on Day 1.
| BG002 | Part 1- Cohort 3: GSK3732394 80 mg | Healthy adult participants were administered a single SC dose of blinded GSK3732394 80 mg on Day 1. |
| BG003 | Part 1- Placebo | Healthy adult participants were administered a single SC dose of blinded GSK3732394 matching placebo on Day 1 in cohorts 1, 2, and 3. |
| BG004 | Part 1- Cohort 4: GSK3732394 | Healthy adult participants were planned to be administered a single SC dose of blinded GSK3732394 |
| BG005 | Part 1- Cohort 5: GSK3732394 | Healthy adult participants were planned to be administered a single SC dose of blinded GSK3732394. |
| BG006 | Part 1- Cohort 6: GSK3732394 | Healthy adult participants were planned to be administered a single SC dose of blinded GSK3732394. |
| BG007 | Part 2- Cohort 1: GSK3732394 | Healthy adult participants were planned to be administered a weekly dose of SC GSK3732394 on Days 1, 8, 15 and 22. |
| BG008 | Part 2- Cohort 2: GSK3732394 | Healthy adult participants were planned to be administered a weekly dose of SC GSK3732394 on Days 1, 8, 15 and 22 |
| BG009 | Part 2- Cohort 3: GSK3732394 | Healthy adult participants were planned to be administered a weekly dose of SC GSK3732394 on Days 1, 8, 15 and 22. |
| BG010 | Part 2: Placebo | Healthy adult participants were planned to be administered a weekly dose of SC GSK3732394 matching placebo on Days 1, 8, 15 and 22 in cohorts 1, 2 and 3. |
| BG011 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| Years |
|
| Sex: Female, Male | Only data for Part 1 is presented as study was terminated during Part 1; Part 2 was not initiated. | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Only data for Part 1 is presented as study was terminated during Part 1; Part 2 was not initiated. | Count of Participants | Participants |
|
| ID | Title | Description |
|---|
| OG000 | Part 1- Cohort 1: GSK3732394 10 mg | Healthy adult participants were administered a single subcutaneous (SC) dose of blinded GSK3732394 10 milligrams (mg) on Day 1. |
| OG001 | Part 1- Cohort 2: GSK3732394 20 mg | Healthy adult participants were administered a single SC dose of blinded GSK3732394 20 mg on Day 1. |
| OG002 | Part 1- Cohort 3: GSK3732394 80 mg | Healthy adult participants were administered a single SC dose of blinded GSK3732394 80 mg on Day 1. |
| OG003 | Part 1- Placebo | Healthy adult participants were administered a single SC dose of blinded GSK3732394 matching placebo on Day 1 in cohorts 1, 2, and 3. |
| OG004 | Part 1- Cohort 4: GSK3732394 | Healthy adult participants were planned to be administered a single SC dose of blinded GSK3732394 |
| OG005 | Part 1- Cohort 5: GSK3732394 | Healthy adult participants were planned to be administered a single SC dose of blinded GSK3732394. |
| OG006 | Part 1- Cohort 6: GSK3732394 | Healthy adult participants were planned to be administered a single SC dose of blinded GSK3732394. |
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| Primary | Part 2: Number of Participants With Non-SAEs and SAEs | 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. A SAE is defined as any untoward medical occurrence that, at any dose: results in death and is life-threatening which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly, or any other situation that require medical or scientific judgement. All AEs were planned to be collected from the start of treatment until the follow-up visit. | Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Up to Day 49 |
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| Primary | Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Blood samples were collected for the analysis of following clinical chemistry parameters: Glucose, alkaline phosphatase, alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), direct bilirubin, total bilirubin, calcium, creatinine, potassium, lipase and sodium. The clinical chemistry abnormalities were graded using the Division of Acquired immunodeficiency syndrome (DAIDS) criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severe condition. Baseline is defined as the latest pre-dose assessment. Number of participants with clinical chemistry parameters by maximum grade increase post-Baseline is presented. | Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Count of Participants | Participants | Up to Day 28 |
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| Primary | Part 2: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline | Blood samples were planned to be collected for the analysis of the following clinical chemistry parameters: Glucose, alkaline phosphatase, ALT, amylase, AST, direct and total bilirubin, calcium, creatinine, potassium, lipase and sodium. Baseline is defined as the latest pre-dose assessment. | Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Up to Day 49 |
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| Primary | Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Blood samples were collected for the analysis of following hematology parameters: Cluster of differentiation (CD) 4 cells, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. The hematology abnormalities were graded using the DAIDS criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severe condition. Baseline is defined as the latest pre-dose assessment. Number of participants with hematology parameters by maximum grade increase post-Baseline is presented. | Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Count of Participants | Participants | Up to Day 28 |
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| Primary | Part 2: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline | Blood samples were planned to be collected for the analysis of the following hematology parameters: CD4 cells, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. Baseline is defined as the latest pre-dose assessment. | Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Up to Day 49 |
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| Primary | Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Urine samples were collected for the analysis of urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. The urinalysis abnormalities were graded using the DAIDS criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Baseline is defined as the latest pre-dose assessment. Number of participants with urinalysis parameters by any increase in discrete or character values post Baseline is presented. | Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Count of Participants | Participants | Up to Day 28 |
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| Primary | Part 2: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline | Urine samples were planned to be collected for the analysis of urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. Baseline is defined as the latest pre-dose assessment. | Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Up to Day 49 |
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| Primary | Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline | Pulse rate was measured in a semi-supine position after 5 minutes of rest. Participants are counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose value category are unchanged (e.g., High to High), or whose value became within range, are recorded in the "To within Range or No Change" category. Participants with missing Baseline value are assumed to have within range value. Participants were counted twice if the participant had both values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment. Number of participants with pulse rate change to low or to high and no change post Baseline is presented. | Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Count of Participants | Participants | Up to Day 28 |
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| Primary | Part 2: Number of Participants With Worst Case Pulse Rate Post Baseline | Pulse rate was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment. | Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Up to Day 49 |
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| Primary | Part 1: Change From Baseline in Body Temperature | Body temperature was measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. | Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Mean | Standard Deviation | Degrees Celsius | Baseline and at Day 1 (1, 2, 4, 8, 12 hours), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
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| Primary | Part 2: Change From Baseline in Body Temperature | Body temperature was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. | Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Baseline and Up to Day 49 |
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| Primary | Part 1: Change From Baseline in Respiratory Rate | Respiratory rate was measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. | Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Mean | Standard Deviation | Breaths per minute | Baseline and at Day 1 (1, 2, 4, 8, 12 hours), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
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| Primary | Part 2: Change From Baseline in Respiratory Rate | Respiratory rate was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. | Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Baseline and Up to Day 49 |
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| Primary | Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline | SBP and DBP was measured in a semi-supine position after 5 minutes of rest. Participants are counted in the worst case category that their value changes to low, within range or no change, or high), unless there is no change in their category. Participants whose value category are unchanged (e.g., High to High), or whose value became within range, are recorded in the "To within Range or No Change" category. Participants with missing Baseline value are assumed to have within range value. Participants were counted twice if the participant had both values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment. Number of participants with SBP and DBP change to low and to high and no change post Baseline is presented. | Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Count of Participants | Participants | Up to Day 28 |
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| Primary | Part 2: Number of Participants With Worst Case SBP and DBP Post Baseline | SBP and DBP was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment. | Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Up to Day 49 |
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| Primary | Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings | A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of 5 minutes. Twelve lead ECGs were obtained by using an automated ECG machine. Number of participants with clinical significant abnormal ECG findings are presented. | Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Count of Participants | Participants | Pre-dose, 4, 12 hours on Day 1, 24 hours on Day 2, Days 8, 14, 17 and 28 |
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| Primary | Part 2: Number of Participants With Clinical Significant Abnormal ECG Findings | 12-lead ECG recordings was planned to be measured. | Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Up to Day 49 |
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| Secondary | Part 1: Area Under the Plasma Concentration Time Curve From Zero to t (AUC[0-t]) Following Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. | PK Population consisted of all participants in the Safety population who had at least 1 non-missing PK assessment. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*micrograms per milliliter | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
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| Secondary | Part 2: AUC(0-t) After Repeat Dosing of GSK3732394 in First Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. | Posted | Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7 |
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| Secondary | Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) Following Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*micrograms per milliliter | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
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| Secondary | Part 2: AUC(0-infinity) After Repeat Dosing of GSK3732394 in First Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. | Posted | Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7 |
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| Secondary | Part 1: Maximum Observed Concentration (Cmax) Following Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. | Posted | Geometric Mean | Geometric Coefficient of Variation | Micrograms per milliliter | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
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| Secondary | Part 2: Cmax After Repeat Dosing of GSK3732394 in First Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. | Posted | Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7 |
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| Secondary | Part 2: Cmax After Repeat Dosing of GSK3732394 in Last Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. | Posted | Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28 |
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| Secondary | Part 1: Time of Occurrence of Cmax (Tmax) After Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were calculated using standard non-compartmental analysis. | PK Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. | Posted | Median | Full Range | Hours | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
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| Secondary | Part 2: Tmax After Repeat Dosing of GSK3732394 in First Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. | Posted | Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7 |
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| Secondary | Part 2: Tmax After Repeat Dosing of GSK3732394 in Last Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. | Posted | Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28 |
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| Secondary | Part 1: Lag Time Before Observation of Drug Concentrations (Tlag) After Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were calculated using standard non-compartmental analysis. | PK Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. | Posted | Median | Full Range | Hours | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
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| Secondary | Part 2: Tlag After Repeat Dosing of GSK3732394 in First Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. | Posted | Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7 |
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| Secondary | Part 1: Last Observable Concentration (Clast) After Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. | Posted | Geometric Mean | Geometric Coefficient of Variation | Micrograms per milliliter | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
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| Secondary | Part 1: Time of Last Observable Concentration (Tlast) After Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. | Posted | Median | Full Range | Hours | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
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| Secondary | Part 1: Apparent Terminal Phase Half-life (t1/2) After Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. | Posted | Median | Full Range | Hours | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
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| Secondary | Part 2: T1/2 After Repeat Dosing of GSK3732394 in Last Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. | Posted | Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28 |
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| Secondary | Part 1: Apparent Clearance (CL/F) After Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters per hour | Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
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| Secondary | Part 2: CL/F After Repeat Dosing of GSK3732394 in Last Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. | Posted | Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28 |
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| Secondary | Part 2: Area Under the Concentration Time Curve at Steady State Within the Dosing Interval (AUC[0-tau]) After Repeat Dosing of GSK3732394 in Last Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. | Posted | Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28 |
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|
| Secondary | Part 2: Trough Concentration (Ctrough) After Repeat Dosing of GSK3732394 in Last Week | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. | PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. | Posted | Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28 |
|
|
| Secondary | Part 2: Accumulation Ratio Using AUC(0-tau) (RAUC[0-tau]) After Repeat Dosing of GSK3732394 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. RAUC(0-tau) was planned to be calculated as the ratio of AUC(0-tau) on week 4 to AUC(0-tau) on week 1 . | PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. | Posted | Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28 |
|
|
| Secondary | Part 2: Accumulation Ratio Using Cmax (RCmax) After Repeat Dosing of GSK3732394 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. RCmax was planned to be calculated as the ratio of Cmax on Week 4 to Cmax on Week 1. | PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. | Posted | Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28 |
|
|
| Secondary | Part 2: Accumulation Ratio Using Ctrough (RCtrough) After Repeat Dosing of GSK3732394 | Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. RCtrough was planned to be calculated as the ratio of Ctrough on Week 4 to Ctrough on Week 1. | PK Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. | Posted | Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28 |
|
|
| Secondary | Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for Pharmacodynamic (PD) analysis of CD4 receptors occupied by GSK3732394 on CD4+ T cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. | Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Mean | Standard Deviation | Percentage of CD4 receptor occupancy | Baseline, Day 1 (0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
|
|
|
| Secondary | Part 2: Change From Baseline in Percent of CD4 RO After Multiple Dose Administration of GSK3732394 | Blood samples were planned to be collected at indicated time points for PD analysis of CD4 receptors occupied by GSK3732394 on CD4+ T cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. | Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Baseline and up to Day 49 |
|
|
| Secondary | Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for analysis of CD3+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. | Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Mean | Standard Deviation | 10^9 cells per Liter | Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28 |
|
|
|
| Secondary | Part 2: Change From Baseline in CD3+ Cells Following Multiple Dose Administration of GSK3732394 | Blood samples were planned to be collected at indicated time points for analysis of CD3+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. | Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Baseline and up to Day 49 |
|
|
| Secondary | Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for analysis of CD4+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. | Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Mean | Standard Deviation | 10^6 cells per Liter | Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28 |
|
|
|
| Secondary | Part 2: Change From Baseline in CD4+ Cells Following Multiple Dose Administration of GSK3732394 | Blood samples were planned to be collected at indicated time points for analysis of CD4+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. | Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Baseline and up to Day 49 |
|
|
| Secondary | Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for analysis of CD8+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. | Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Mean | Standard Deviation | 10^6 cells per Liter | Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28 |
|
|
|
| Secondary | Part 2: Change From Baseline in CD8+ Cells Following Multiple Dose Administration of GSK3732394 | Blood samples were planned to be collected at indicated time points for analysis of CD8+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. | Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Baseline and up to Day 49 |
|
|
| Secondary | Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394 | Blood samples were collected at indicated time points for analysis of CD4+ cell MFI. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value. | Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles). Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Median | Full Range | Median fluorescence intensity | Baseline, Day 1 (0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28 |
|
|
|
| Secondary | Part 2: Change From Baseline in CD4+ Cell MFI Following Multiple Dose Administration of GSK3732394 | Blood samples were planned to be collected at indicated time points for analysis of CD4+ cell MFI. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. | Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Baseline and up to Day 49 |
|
|
| Secondary | Part 1: Number of Participants With Anti-GSK3732394 Antibodies on Day 28 | Serum samples were collected to analyze antibodies against GSK3732394. The presence of anti-GSK3732394 antibodies was determined in serum samples using a validated bioanalytical method, which included a screening assay, confirmation assay and titer analysis. Positive samples were further characterized with additional assays to determine the specificity of the anti-GSK3732394 antibodies. Number of participants with presence of anti-GSK3732394 antibodies are presented. | Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Count of Participants | Participants | Day 28 |
|
|
|
| Secondary | Part 2: Number of Participants With Anti-GSK3732394 Antibodies | Serum samples were planned to be collected to analyze antibodies against GSK3732394. | Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Up to Day 49 |
|
|
| Secondary | Part 1: Titer of Anti-drug Antibodies (ADAs) Against GSK3732394 on Day 28 | Serum samples were collected to analyze the titers of antibodies against GSK3732394. The presence of anti-GSK3732394 antibodies was determined in serum samples using a validated bioanalytical method, which included a screening assay, confirmation assay and titer analysis. Positive samples were further characterized with additional assays to determine the specificity of the anti-GSK3732394 antibodies. Positive samples were titrated to obtain the titers of antibodies. | Safety Population. Data was not collected for Cohort 4 to 6, as the study was terminated after Part 1-Cohort 3 and hence no participants were enrolled. Only those participants with data available at the specified data points were analyzed. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Median | Full Range | Titer | Day 28 |
|
|
|
| Secondary | Part 2: Titer of ADAs Against GSK3732394 | Serum samples were planned to be collected to analyze the titers of antibodies against GSK3732394. | Safety Population. Data was not collected for Part 2 as the study was terminated after Part 1-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan. | Posted | Up to Day 49 |
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 4 |
| 6 |
| EG001 | Part 1- Cohort 2: GSK3732394 20 mg | Healthy adult participants were administered a single SC dose of blinded GSK3732394 20 mg on Day 1. | 0 | 6 | 0 | 6 | 4 | 6 |
| EG002 | Part 1- Cohort 3: GSK3732394 80 mg | Healthy adult participants were administered a single SC dose of blinded GSK3732394 80 mg on Day 1. | 0 | 6 | 0 | 6 | 4 | 6 |
| EG003 | Part 1- Placebo | Healthy adult participants were administered a single SC dose of blinded GSK3732394 matching placebo on Day 1 in cohorts 1, 2, and 3. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG004 | Part 1- Cohort 4: GSK3732394 | Healthy adult participants were planned to be administered a single SC dose of blinded GSK3732394 | 0 | 0 | 0 | 0 | 0 | 0 |
| EG005 | Part 1- Cohort 5: GSK3732394 | Healthy adult participants were planned to be administered a single SC dose of blinded GSK3732394. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG006 | Part 1- Cohort 6: GSK3732394 | Healthy adult participants were planned to be administered a single SC dose of blinded GSK3732394. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG007 | Part 2- Cohort 1: GSK3732394 | Healthy adult participants were planned to be administered a weekly dose of SC GSK3732394 on Days 1, 8, 15 and 22. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG008 | Part 2- Cohort 2: GSK3732394 | Healthy adult participants were planned to be administered a weekly dose of SC GSK3732394 on Days 1, 8, 15 and 22 | 0 | 0 | 0 | 0 | 0 | 0 |
| EG009 | Part 2- Cohort 3: GSK3732394 | Healthy adult participants were planned to be administered a weekly dose of SC GSK3732394 on Days 1, 8, 15 and 22. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG010 | Part 2: Placebo | Healthy adult participants were planned to be administered a weekly dose of SC GSK3732394 matching placebo on Days 1, 8, 15 and 22 in cohorts 1, 2 and 3. | 0 | 0 | 0 | 0 | 0 | 0 |
| Chest pain | General disorders | MedDRA 22.1 | Systematic Assessment |
|
| Injection site bruising | General disorders | MedDRA 22.1 | Systematic Assessment |
|
| Vessel puncture site pain | General disorders | MedDRA 22.1 | Systematic Assessment |
|
| Vessel puncture site swelling | General disorders | MedDRA 22.1 | Systematic Assessment |
|
| Folliculitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
|
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
|
| Transaminases increased | Investigations | MedDRA 22.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 22.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Drug eruption | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
| Miliaria | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
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.
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| Glucose; increase to Grade 2 |
|
| Glucose; increase to Grade 3 |
|
| Glucose; increase to Grade 4 |
|
| Alkaline phosphatase; increase to Grade 1 |
|
| Alkaline phosphatase; increase to Grade 2 |
|
| Alkaline phosphatase; increase to Grade 3 |
|
| Alkaline phosphatase; increase to Grade 4 |
|
| ALT, increase to Grade 1 |
|
| ALT, increase to Grade 2 |
|
| ALT, increase to Grade 3 |
|
| ALT, increase to Grade 4 |
|
| Amylase; increase to Grade 1 |
|
| Amylase; increase to Grade 2 |
|
| Amylase; increase to Grade 3 |
|
| Amylase; increase to Grade 4 |
|
| AST; increase to Grade 1 |
|
| AST; increase to Grade 2 |
|
| AST; increase to Grade 3 |
|
| AST; increase to Grade 4 |
|
| Direct bilirubin; increase to Grade 1 |
|
| Direct bilirubin; increase to Grade 2 |
|
| Direct bilirubin; increase to Grade 3 |
|
| Direct bilirubin; increase to Grade 4 |
|
| Total bilirubin; increase to Grade 1 |
|
| Total bilirubin; increase to Grade 2 |
|
| Total bilirubin; increase to Grade 3 |
|
| Total bilirubin; increase to Grade 4 |
|
| Calcium; increase to Grade 1 |
|
| Calcium; increase to Grade 2 |
|
| Calcium; increase to Grade 3 |
|
| Calcium; increase to Grade 4 |
|
| Creatinine; increase to Grade 1 |
|
| Creatinine; increase to Grade 2 |
|
| Creatinine; increase to Grade 3 |
|
| Creatinine; increase to Grade 4 |
|
| Potassium; increase to Grade 1 |
|
| Potassium; increase to Grade 2 |
|
| Potassium; increase to Grade 3 |
|
| Potassium; increase to Grade 4 |
|
| Lipase: increase to Grade 1 |
|
| Lipase: increase to Grade 2 |
|
| Lipase: increase to Grade 3 |
|
| Lipase: increase to Grade 4 |
|
| Sodium; increase to Grade 1 |
|
| Sodium; increase to Grade 2 |
|
| Sodium; increase to Grade 3 |
|
| Sodium; increase to Grade 4 |
|
| CD4; increase to grade 2 |
|
| CD4; increase to grade 3 |
|
| CD4; increase to grade 4 |
|
| Hemoglobin; increase to grade 1 |
|
| Hemoglobin; increase to grade 2 |
|
| Hemoglobin; increase to grade 3 |
|
| Hemoglobin; increase to grade 4 |
|
| Lymphocytes; increase to grade 1 |
|
| Lymphocytes; increase to grade 2 |
|
| Lymphocytes; increase to grade 3 |
|
| Lymphocytes; increase to grade 4 |
|
| Neutrophils; increase to grade 1 |
|
| Neutrophils; increase to grade 2 |
|
| Neutrophils; increase to grade 3 |
|
| Neutrophils; increase to grade 4 |
|
| Platelets; increase to grade 1 |
|
| Platelets; increase to grade 2 |
|
| Platelets; increase to grade 3 |
|
| Platelets; increase to grade 4 |
|
| Leukocytes; increase to grade 1 |
|
| Leukocytes; increase to grade 2 |
|
| Leukocytes; increase to grade 3 |
|
| Leukocytes; increase to grade 4 |
|
| Glucose; any increase |
|
| Ketones; any increase |
|
| Leukocyte esterase; any increase |
|
| Nitrite; any increase |
|
| Occult blood; any increase |
|
| Protein; any increase |
|
| Urobilinogen; any increase; |
|
| To high |
|
| No change |
|
|
| Day 1: 2 hours; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 1: 4 hours; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 1: 8 hours; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 1: 12 hours; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 2; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 3; n = 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 4; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 5; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 6; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 7; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 8; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 9; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 10; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 11; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 12; n= 6, 5, 6, 6, 0, 0, 0 |
|
|
| Day 13; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 14; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 17; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 21; n= 6, 5, 6, 6, 0, 0, 0 |
|
|
| Day 24; n= 6, 5, 6, 6, 0, 0, 0 |
|
|
| Day 28; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
|
| Day 1: 2 hours; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 1: 4 hours; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 1: 8 hours; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 1: 12 hours; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 2; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 3; n = 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 4; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 5; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 6; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 7; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 8; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 9; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 10; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 11; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 12; n= 6, 5, 6, 6, 0, 0, 0 |
|
|
| Day 13; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 14; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 17; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| Day 21; n= 6, 5, 6, 6, 0, 0, 0 |
|
|
| Day 24; n= 6, 5, 6, 6, 0, 0, 0 |
|
|
| Day 28; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| SBP: To high |
|
| SBP: No change |
|
| DBP: To low |
|
| DBP: To high |
|
| DBP: No change |
|
| Day 1- 4 hours |
|
| Day 1- 12 hours |
|
| Day 2- 24 hours |
|
| Day 8 |
|
| Day 14 |
|
| Day 17 |
|
| Day 28 |
|
|
| %CD4 RO; Day 1- 1 hour; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 1- 2 hours; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 1- 4 hours; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 1- 8 hours; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 1- 12 hours; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 2; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 3; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 4; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 5; n= 6, 5, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 6; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 7; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 8; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 9; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 10; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 11; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 12; n= 5, 6, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 13; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 14; n= 6, 6, 6, 5, 0, 0, 0 |
|
|
| %CD4 RO; Day 17; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 21; n= 6, 5, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 24; n= 6, 5, 6, 6, 0, 0, 0 |
|
|
| %CD4 RO; Day 28; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
|
| CD3+: Day 3; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| CD3+: Day 5; n= 6, 6, 5, 6, 0, 0, 0 |
|
|
| CD3+; Day 8; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| CD3+; Day 11; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| CD3+; Day 14; n= 6, 6, 6, 5, 0, 0, 0 |
|
|
| CD3+; Day 17; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| CD3+; Day 21; n= 6, 5, 6, 6, 0, 0, 0 |
|
|
| CD3+; Day 24; n= 6, 5, 6, 6, 0, 0, 0 |
|
|
| CD3+; Day 28; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
|
| CD4+: Day 3; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| CD4+: Day 5; n= 6, 6, 5, 6, 0, 0, 0 |
|
|
| CD4+; Day 8; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| CD4+; Day 11; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| CD4+; Day 14; n= 6, 6, 6, 5, 0, 0, 0 |
|
|
| CD4+; Day 17; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| CD4+; Day 21; n= 6, 5, 6, 6, 0, 0, 0 |
|
|
| CD4+; Day 24; n= 6, 5, 6, 6, 0, 0, 0 |
|
|
| CD4+; Day 28; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
|
| CD8+; Day 3;n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| CD8+: Day 5; n= 6, 6, 5, 6, 0, 0, 0 |
|
|
| CD8+; Day 8; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| CD8+; Day 11; n= 6, 6, 6, 6, 0, 0, 0 |
|
|
| CD8+; Day 14; n= 6, 6, 6, 5, 0, 0, 0 |
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| CD8+; Day 17; n= 6, 6, 6, 6, 0, 0, 0 |
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| CD8+; Day 21; n= 6, 5, 6, 6, 0, 0, 0 |
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| CD8+; Day 24; n= 6, 5, 6, 6, 0, 0, 0 |
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| CD8+; Day 28; n= 6, 6, 6, 6, 0, 0, 0 |
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| CD4+ MFI: Day 1- 1 hour; n= 6, 6, 6, 6, 0, 0, 0 |
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| CD4+ MFI; Day 1- 2 hours; n= 6, 6, 6, 6, 0, 0, 0 |
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| CD4+ MFI; Day 1- 4 hours; n= 6, 6, 6, 6, 0, 0, 0 |
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| CD4+ MFI; Day 1- 8 hours; n= 6, 6, 6, 6, 0, 0, 0 |
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| CD4+ MFI; Day 1- 12 hours; n= 6, 6, 6, 6, 0, 0, 0 |
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| CD4+ MFI; Day 2; n= 6, 6, 6, 6, 0, 0, 0 |
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| CD4+ MFI; Day 3; n= 6, 6, 6, 6, 0, 0, 0 |
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| CD4+ MFI; Day 4; n= 6, 6, 6, 6, 0, 0, 0 |
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| CD4+ MFI; Day 5; n= 6, 5, 6, 6, 0, 0, 0 |
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| CD4+ MFI; Day 6; n= 6, 6, 6, 6, 0, 0, 0 |
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| CD4+ MFI: Day 7; n= 6, 6, 6, 6, 0, 0, 0 |
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| CD4+ MFI: Day 8; n= 6, 6, 6, 6, 0, 0, 0 |
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| CD4+ MFI; Day 9; n= 6, 6, 6, 6, 0, 0, 0 |
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| CD4+ MFI; Day 10; n= 6, 6, 6, 6, 0, 0, 0 |
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| CD4+ MFI; Day 11; n= 6, 6, 6, 6, 0, 0, 0 |
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| CD4+ MFI; Day 12; n= 5, 6, 6, 6, 0, 0, 0 |
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| CD4+ MFI; Day 13; n= 6, 6, 6, 6, 0, 0, 0 |
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| CD4+ MFI; Day 14; n= 6, 6, 6, 5, 0, 0, 0 |
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| CD4+ MFI; Day 17; n= 6, 6, 6, 6, 0, 0, 0 |
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| CD4+ MFI; Day 21;n= 6, 5, 6, 6, 0, 0, 0 |
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| CD4+ MFI: Day 24; n= 6, 5, 6, 6, 0, 0, 0 |
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| CD4+ MFI: Day 28; n= 6, 6, 6, 6, 0, 0, 0 |
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