A Multi-dose Study of ARC-520 in Patients With Hepatitis... | NCT02604199

NCT02604199

ID	Type	Description	Link
2014-004145-27	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
PBO Low Dose	Placebo Comparator	0.9% normal saline, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period	Other: placebo Drug: entecavir Drug: tenofovir Drug: antihistamine
PBO High Dose	Placebo Comparator	0.9% normal saline, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period	Other: placebo Drug: entecavir Drug: tenofovir Drug: antihistamine
ARC-520 Injection 1 mg/kg	Experimental	Intravenous ARC-520 at 1.0 mg/kg, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period	Drug: ARC-520 Injection Drug: entecavir Drug: tenofovir Drug: antihistamine
ARC-520 Injection 2 mg/kg	Experimental	Intravenous ARC-520 at 2.0 mg/kg, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period	Drug: ARC-520 Injection Drug: entecavir Drug: tenofovir Drug: antihistamine

Interventions

Name	Type	Description	Arm Group Labels	Other Names
ARC-520 Injection	Drug	ARC-520 Injection was administered concomitantly, IV with 0.9% normal saline using an infusion rate of 0.4 mL/min for study treatment and 3.6 mL/min for saline.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) at Day 113	Change From Baseline in log qHBsAg at Day 113 in response to multiple doses of ARC-520 versus placebo, using a a mixed effect model for repeated measures (MMRM). Includes parameter baseline as a continuous covariate, and treatment and visit as fixed factors, interaction of treatment and visit, and interaction of parameter baseline and visit.	Baseline, Day 113

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time	Change From Baseline in log qHBsAg at Day 113 in response to multiple doses of ARC-520 versus placebo, using a a mixed effect model for repeated measures (MMRM). Includes parameter baseline as a continuous covariate, and treatment and visit as fixed factors, interaction of treatment and visit, and interaction of parameter baseline and visit.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female, 18 to 75 years of age
Written informed consent
No clinically significant abnormalities at screening/pre-dose 12-lead ECG assessment
No new abnormal finding of clinical relevance at the screening evaluation.
Diagnosis of HBeAg negative, immune active, chronic HBV infection
> 2 months of continuous treatment with daily, oral entecavir or tenofovir
Willingness to continue taking entecavir or tenofovir throughout the study.
Must use 2 effective methods of contraception (double barrier contraception or hormonal contraceptive along with a barrier contraceptive) (both male and female partners)

Exclusion Criteria:

Pregnant or lactating
Acute signs of hepatitis/other infection within 4 weeks of screening
Antiviral therapy other than entecavir or tenofovir within 3 months of screening
Prior treatment with interferon in the last 3 years.
Use within the last 6 months or anticipated requirement for anticoagulants, corticosteroids, immunomodulators, or immunosuppressants.
Use of prescription medication within 14 days prior to treatment administration except: topical products without systemic absorption, statins (except rosuvastatin), hypertension medications, or hormonal contraceptives.
Depot injection or implant of any drug within 3 months prior to treatment administration, except injectable/implantable birth control.
Diagnosis of diabetes mellitus.
History of autoimmune disease especially autoimmune hepatitis.
Human immunodeficiency virus (HIV) infection.
Sero-positive for Hepatitis C Virus (HCV), and/or a history of delta virus hepatitis.
Hypertension defined as blood pressure > 150/100 mmHg
History of cardiac rhythm disturbances
Family history or congenital long QT syndrome, Brugada syndrome or unexplained sudden cardiac death
Symptomatic heart failure, unstable angina, myocardial infarction, severe cardiovascular disease within 6 months prior to study entry.
History of malignancy except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer.
Has had a major surgery within 3 months of screening.
History of alcohol and/or drug abuse < 12 months from screening.
Regular uses of alcohol within 6 months prior to screening (ie, more than 14 units of alcohol per week).
Evidence of severe systemic acute inflammation, sepsis, or hemolysis.
Diagnosed with a significant psychiatric disorder.
Use of recreational drugs, such as marijuana, within 3 months prior to screening
Use of drugs such as cocaine, phencyclidine (PCP), and methamphetamines, within 1 year prior to screening.
History of allergy to bee sting.
Use of investigational agents or devices within 30 days prior to planned study dosing or current participation in an investigational study.
Clinically significant history or presence of any gastrointestinal pathology, unresolved gastrointestinal symptoms, liver or kidney disease.
Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction.
Clinically significant history or presence of poorly controlled/uncontrolled systemic disease.
History of fever within 2 weeks of screening.
Immunized with a live attenuated vaccine within 7 days prior to dosing or planned vaccination (excluding flu vaccine by injection).
Presence of any medical or psychiatric condition or social situation that impacts compliance or results in additional safety risk.
Participated in excessive exercise/physical activity within 7 days of screening or planned during the trial.
History of coagulopathy/stroke within past 6 months, and/or concurrent anticoagulant medication(s).

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Research Site 1		Hong Kong		999077	China
Research Site 2

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	PBO Low Dose	0.9% normal saline, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period
FG001	PBO High Dose

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

ARC-520 Injection 1 mg/kg

ARC-520 Injection 2 mg/kg

0.9% normal saline, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	PBO Low Dose	0.9% normal saline, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period
BG001	PBO High Dose	0.9% normal saline, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period
BG002	ARC-520 Injection 1 mg/kg	Intravenous ARC-520 at 1.0 mg/kg, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period
BG003	ARC-520 Injection 2 mg/kg	Intravenous ARC-520 at 2.0 mg/kg, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG000-0.070± 0.033 OG001-0.157± 0.036 OG002-0.379± 0.033

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		MMRM	Within-subject covariance is unstructured.	0.0810	Mixed effect model repeat measurement (MMRM) includes terms of parameter baseline as continuous covariate, and treatment and visit as fixed factors, interaction of treatment and visit, and interaction of parameter baseline and visit.	LS Mean Difference	-0.086	Standard Error of the Mean	0.048	2-Sided	95	-0.183	0.011					Superiority

Secondary

Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) Over Time

Intent to treat population: all participants who received at least 1 dose of study drug and had valid qHBsAg values at baseline and at least one time point on or after the Day 15 visit.

Posted

Least Squares Mean

Standard Error

log IU/mL

Baseline, Day 15, 29, 43, 57, 71, 85, 99

ID	Title	Description
OG000	Placebo	Placebo (low dose or high dose) 0.9% normal saline, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period
OG001	ARC-520 Injection 1 mg/kg	Intravenous ARC-520 at 1.0 mg/kg, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period
OG002	ARC-520 Injection 2 mg/kg	Intravenous ARC-520 at 2.0 mg/kg, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period

Secondary

Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs

An AE is any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. An SAE is any AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is a medically important event or reaction. A treatment emergent AE (TEAE) was defined as an AE that was not present prior to the first study medication administration and started at/after the time of initiation of administration of study medication, or an AE which was present prior to initiation of study medication administration, which increased in severity after study medication administration.

Safety Population: all participants who received at least 1 dose of study treatment or placebo, and had at least 1 post-dose safety assessment.

Posted

Count of Participants

Participants

Through Day 169

ID	Title	Description
OG000	PBO Low Dose	0.9% normal saline, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period
OG001	PBO High Dose	0.9% normal saline, once every 4 weeks for 4 doses plus daily oral entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg) throughout the study period

Secondary

Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24)

Due to the early suspension and termination of the study, all pharmacokinetic analyses were removed from the initial statistical analysis plan for this study. No collected samples were analyzed and all were destroyed.

Posted