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
Overview
- Phase
- Phase 2
- Intervention
- ARB-001467
- Conditions
- Hepatitis B, Chronic
- Sponsor
- Arbutus Biopharma Corporation
- Enrollment
- 36
- Locations
- 4
- Primary Endpoint
- 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.
- Status
- Completed
- Last Updated
- 7 years ago
Overview
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.
Investigators
Eligibility Criteria
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.
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.
Arms & Interventions
0.2 mg/kg ARB-001467 or Placebo
HBeAg-negative subjects randomized 3:1 to receive ARB-001467 at 0.2 mg/kg versus placebo once a month for 3 months
Intervention: ARB-001467
0.2 mg/kg ARB-001467 or Placebo
HBeAg-negative subjects randomized 3:1 to receive ARB-001467 at 0.2 mg/kg versus placebo once a month for 3 months
Intervention: Placebo
0.4 mg/kg ARB-001467 or Placebo
HBeAg-negative subjects randomized 3:1 to receive ARB-001467 at 0.4 mg/kg versus placebo once a month for 3 months
Intervention: ARB-001467
0.4 mg/kg ARB-001467 or Placebo
HBeAg-negative subjects randomized 3:1 to receive ARB-001467 at 0.4 mg/kg versus placebo once a month for 3 months
Intervention: Placebo
ARB-001467 or Placebo
HBeAg-positive subjects randomized 3:1 to receive ARB-001467 at 0.4 mg/kg versus placebo once a month for 3 months
Intervention: ARB-001467
ARB-001467 or Placebo
HBeAg-positive subjects randomized 3:1 to receive ARB-001467 at 0.4 mg/kg versus placebo once a month for 3 months
Intervention: Placebo
0.4 mg/kg ARB-001467
HBeAg-negative subjects receive ARB-001467 at. 0.4 mg/kg (open label) bi-weekly for 5 treatments and then subjects with HBsAg ≤1000 IU/mL AND ≥1.0 log10 decrease from baseline at Day 71 will continue monthly dosing through 48 weeks
Intervention: ARB-001467
Outcomes
Primary Outcomes
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.
Time Frame: 28 days post last infusion
To evaluate the safety and tolerability of multiple doses of ARB-001467 in HBeAg-negative and HBeAg-positive subjects with chronic Hepatitis B virus infection who are receiving nucleos(t)ide analogue therapy
Secondary Outcomes
- 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.(Up to 36 Weeks)
- 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).(Up to 36 Weeks)
- 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).(Up to 36 Weeks)
- 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).(Up to 36 Weeks)
- Evaluate antiviral activity of ARB 001467 for up to 72 weeks after the first dose of study treatment.(Up to 18 months)