Clinical trial NCT02631096: Study of ARB-001467 in Subjects With Chronic HBV Infection Receiving Nucleos(t)Ide Analogue Therapy
Official title: A Phase 2a Single-Blind, Randomized, Placebo-Controlled Study Evaluating the Safety, Anti Viral Activity, and Pharmacokinetics of ARB-001467 in Non Cirrhotic, HBeAg Negative and Positive Subjects With Chronic HBV Infection Receiving Nucleos(t)Ide Analogue Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis B, Chronic
Lead sponsor: Arbutus Biopharma Corporation
Sponsor class: INDUSTRY
First posted: 2015-12-15
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is a phase 2a, single blind, randomized, placebo controlled, study evaluating the safety, anti-viral activity, and pharmacokinetics (PK) following multiple doses of intravenous ARB-001467

Detailed description: Approximately 24 subjects will be enrolled in three cohorts: two cohorts of HBeAg-negative subjects and one cohort of HBeAg-positive subjects and 12 HbeAg-negative subjects will be enrolled in cohort 4. All subjects will be non-cirrhotic, with chronic hepatitis B virus (HBV) infection, and will have been receiving nucleos(t)ide-analogue (NA) therapy with entecavir or tenofovir for at least 12 months.

Eligibility criteria: Key Inclusion Criteria:

* Documented chronic HBV infection for ≥12 months prior to Screening Visit.
* Quantitative HBsAg ≥1000 IU/mL at the Screening Visit.
* Subjects currently receiving entecavir and/or tenofovir for ≥12 months and HBV DNA undetectable.

Key Exclusion Criteria:

* Known co-infection with HIV, hepatitis C virus, and hepatitis D virus.
* Receiving or planning to receive systemic immunosuppressive medications during the study or ≤2 months prior to the first dose of study treatment.
* Receiving or planning to receive interferon during the study or ≤12 months prior to the first dose of study treatment.
* Significant immunosuppression from, but not limited to immunodeficiency conditions such as common variable hypogammaglobulinemia.
* Clinical diagnosis of substance abuse with alcohol, narcotics, or cocaine ≤12 months prior to the Screening Visit.
* Any known pre-existing medical or psychiatric condition that could interfere with the subject's ability to provide informed consent or participate in study conduct, or that may confound study findings.

Primary outcomes:
measure: Frequency and severity of treatment-emergent SAEs, discontinuations due to AEs, and laboratory abnormalities, by cohort, through 28 days after the last infusion of study treatment.
timeFrame: 28 days post last infusion
Secondary outcomes:
measure: Evaluate ARB-001467 Maximum plasma concentration (Cmax) at multiple time points from baseline through Day 85; 28 days after the last infusion of study treatment (cohort 1-3) and Week 36 (Cohort 4).
timeFrame: Up to 36 Weeks
measure: Evaluate ARB-001467 Time to maximum plasma concentration (Tmax) at multiple time points from baseline through Day 85; 28 days after the last infusion of study treatment (cohort 1-3) and Week 36 (Cohort 4).
timeFrame: Up to 36 Weeks
measure: Evaluate ARB-001467 Area under the plasma concentration-time curve from the start of infusion to the last measurable concentration (AUC0-t) at multiple time points from baseline through Day 85 (cohort 1-3) and Week 36 (Cohort 4).
timeFrame: Up to 36 Weeks
measure: Evaluate additional parameters for ARB-001467 from plasma concentration-time curve from start of infusion and extrapolated to infinity (AUC0-t), inf) partial, AUCs, T1/2, volume of distribution (VD) and clearance (CL) -baseline through Day 85 or Week 36.
timeFrame: Up to 36 Weeks
measure: Evaluate antiviral activity of ARB 001467 for up to 72 weeks after the first dose of study treatment.
timeFrame: Up to 18 months
Other outcomes:
Locations:
city: Clayton
country: Australia
facility: Monash Health, Gastroenterology and Hepatology
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred, Gastroenterology and Hepatology
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research Ltd
state: Western Australia
city: Auckland
country: New Zealand
facility: Auckland Clinical Studies Ltd
Study officials:
affiliation: Arbutus Biopharma Corporation
name: Patricia Mendez, MD, PhD
role: STUDY_CHAIR
References: