A Multi-dose Study of ARC-520 in Patients With Hepatitis... | NCT02604212

ID	Type	Description	Link
2014-004751-31	EudraCT Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo Low Dose Comparator	Placebo Comparator	Placebo (low dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)	Other: Placebo Drug: entecavir Drug: antihistamine Drug: tenofovir
Placebo High Dose Comparator	Placebo Comparator	Placebo (high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)	Other: Placebo Drug: entecavir Drug: antihistamine Drug: tenofovir
ARC-520 1.0 mg/kg	Experimental	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)	Drug: ARC-520 Drug: entecavir Drug: antihistamine Drug: tenofovir
ARC-520 2.0 mg/kg	Experimental	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)	Drug: ARC-520 Drug: entecavir Drug: antihistamine Drug: tenofovir

Name	Type	Description	Arm Group Labels	Other Names
ARC-520	Drug		ARC-520 1.0 mg/kg ARC-520 2.0 mg/kg
Placebo

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 Log qHBsAg Over Time	Change From Baseline in log qHBsAg up to Day 99 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, Days 15, 29, 43, 57, 71, 85, 99

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 positive, immune active, chronic HBV infection.
> 2months 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).

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

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo Low Dose Comparator	Placebo (low dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
FG001	Placebo High Dose Comparator

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Placebo Low Dose Comparator	Placebo (low dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
BG001	Placebo High Dose Comparator	Placebo (high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
BG002	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
BG003	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
BG004	Total	Total of all reporting groups

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

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.

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 113

ID	Title	Description
OG000	Placebo	Placebo (low or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG002	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Units	Counts
Participants	OG0006 OG0016 OG0028

Title

Denominators

Categories

Title	Measurements
	OG000-0.104± 0.073 OG001-0.146± 0.065 OG002-0.542± 0.061

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		0.6815		LS Mean Difference	-0.042	Standard Error of the Mean	0.102	2-Sided	95	-0.243	0.159					Superiority
OG000 OG002		MMRM		<.0001

Secondary

Change From Baseline in Log qHBsAg Over Time

Change From Baseline in log qHBsAg up to Day 99 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.

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

Mean

Standard Deviation

log IU/mL

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

ID	Title	Description
OG000	Placebo	Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG002	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Secondary

Change From Baseline at Day 15 in Log qHBsAg, by Category

Change in log qHBsAg from baseline, categorized into the following groups: no decrease, decrease > 0 to < 0.5 log IU/mL; decrease 0.5 to 1.0 log IU/mL; decrease > 1.0 log IU/mL, tabulated by dose and treatment for each visit.

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

Mean

Standard Deviation

log IU/mL

Baseline, Day 15

ID	Title	Description
OG000	Placebo	Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG002	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Secondary

Change From Baseline at Day 29 in Log qHBsAg, by Category

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

Mean

Standard Deviation

log IU/mL

Baseline, Day 29

ID	Title	Description
OG000	Placebo	Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG002	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Secondary

Change From Baseline at Day 43 in Log qHBsAg, by Category

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

Mean

Standard Deviation

log IU/mL

Baseline, Day 43

ID	Title	Description
OG000	Placebo	Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG002	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Secondary

Change From Baseline at Day 57 in Log qHBsAg, by Category

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

Mean

Standard Deviation

log IU/mL

Baseline, Day 57

ID	Title	Description
OG000	Placebo	Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG002	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Secondary

Change From Baseline at Day 71 in Log qHBsAg, by Category

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

Mean

Standard Deviation

log IU/mL

Baseline, Day 71

ID	Title	Description
OG000	Placebo	Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG002	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Secondary

Change From Baseline at Day 85 in Log qHBsAg, by Category

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

Mean

Standard Deviation

log IU/mL

Baseline, Day 85

ID	Title	Description
OG000	Placebo	Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG002	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Secondary

Change From Baseline at Day 99 in Log qHBsAg, by Category

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

Mean

Standard Deviation

log IU/mL

Baseline, Day 99

ID	Title	Description
OG000	Placebo	Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG002	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Secondary

Change From Baseline at Day 113 in Log qHBsAg, by Category

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

Mean

Standard Deviation

log IU/mL

Baseline, Day 113

ID	Title	Description
OG000	Placebo	Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG002	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

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 to have a causal relationship with this treatment. A treatment emergent AE (TEAE) was defined as an AE that was not present prior to the first study drug administration and started at/after the time of initiation of administration of study drug, or an AE which was present prior to initiation of study drug administration, which increased in severity after study drug administration. An SAE is any untoward medical occurrence that, at any dose: 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; is a medically important event or reaction.

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

Posted

Number

participants

Through Day 169 (± 3 days)

ID	Title	Description
OG000	Placebo Low Dose Comparator	Placebo (low dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	Placebo High Dose Comparator	Placebo (high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

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

Through 48 hours post-dosing on Day 1 and Day 85

ID	Title	Description
OG000	Placebo	Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG002	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Units	Counts
Participants

Secondary

Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast)

Posted

Through 48 hours post-dosing on Day 1 and Day 85

ID	Title	Description
OG000	Placebo	Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG002	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Units	Counts
Participants

Secondary

Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf)

Posted

Through 48 hours post-dosing on Day 1 and Day 85

ID	Title	Description
OG000	Placebo High Dose Comparator	Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG002	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Units	Counts
Participants

Secondary

Pharmacokinetics of ARC-520: Maximum Observed Plasma Concentration (Cmax)

Posted

Through 48 hours post-dosing on Day 1 and Day 85

ID	Title	Description
OG000	Placebo High Dose Comparator	Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG002	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Units	Counts
Participants

Secondary

Pharmacokinetics of ARC-520: Clearance (CL)

Posted

Through 48 hours post-dosing on Day 1 and Day 85

ID	Title	Description
OG000	Placebo High Dose Comparator	Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG002	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Units	Counts
Participants

Secondary

Pharmacokinetics of ARC-520: Apparent Volume of Distribution (V)

Posted

Through 48 hours post-dosing on Day 1 and Day 85

ID	Title	Description
OG000	Placebo High Dose Comparator	Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG002	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Units	Counts
Participants

Secondary

Pharmacokinetics of ARC-520: Terminal Elimination Rate Constant (Kel)

Posted

Through 48 hours post-dosing on Day 1 and Day 85

ID	Title	Description
OG000	Placebo High Dose Comparator	Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG002	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Units	Counts
Participants

Secondary

Pharmacokinetics of ARC-520: Terminal Elimination Half-Life (t1/2)

Posted

Through 48 hours post-dosing on Day 1 and Day 85

ID	Title	Description
OG000	Placebo High Dose Comparator	Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG001	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)
OG002	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo Low Dose Comparator	Placebo (low dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)	6	4	6
EG001	Placebo High Dose Comparator	Placebo (high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)	5	0	5
EG002	ARC-520 1.0 mg/kg	Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)	10	5	10
EG003	ARC-520 2.0 mg/kg	High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day)	11	3	11

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected5 at risk EG0020 affected10 at risk EG0030 affected11 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected5 at risk EG0021 affected10 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected5 at risk EG0021 affected10 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected5 at risk EG0020 affected10 at risk EG003
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected5 at risk EG0020 affected10 at risk EG003
Chills	General disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected5 at risk EG0021 affected10 at risk EG003
Discomfort	General disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected5 at risk EG0021 affected10 at risk EG003
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected5 at risk EG0021 affected10 at risk EG003
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected5 at risk EG0021 affected10 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected5 at risk EG0020 affected10 at risk EG003
Pharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected5 at risk EG0020 affected10 at risk EG003
Rhinitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected5 at risk EG0020 affected10 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected5 at risk EG0020 affected10 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected5 at risk EG0020 affected10 at risk EG003
Eosinophil count increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected5 at risk EG0020 affected10 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected5 at risk EG0021 affected10 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected5 at risk EG0021 affected10 at risk EG003
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected5 at risk EG0020 affected10 at risk EG003
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected5 at risk EG0021 affected10 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected5 at risk EG0021 affected10 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected6 at risk EG0010 affected5 at risk EG0021 affected10 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected6 at risk EG0010 affected5 at risk EG0020 affected10 at risk EG003

ID	Term
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D018347	Hepadnaviridae Infections
D004266	DNA Virus Infections
D014777	Virus Diseases
D006525	Hepatitis, Viral, Human
D006505	Hepatitis
D008107	Liver Diseases
D004066	Digestive System Diseases

ID	Term
C000717093	ARC-520
C413685	entecavir
D006633	Histamine Antagonists
D000068698	Tenofovir

ID	Term
D018494	Histamine Agents
D018377	Neurotransmitter Agents
D045504	Molecular Mechanisms of Pharmacological Action
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses
D045505	Physiological Effects of Drugs
D063065	Organophosphonates
D009943	Organophosphorus Compounds
D009930	Organic Chemicals
D000225	Adenine
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds