Study of ARB-001467 in Subjects With Chronic HBV Infection Receiving Nucleos(t)Ide Analogue Therapy

NCT02631096 | Completed Phase 2 DMC

• 1 other identifier: ARB-001467-002
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 4

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

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  28 days post last infusion

Secondary Outcomes (5)

• 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 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 antiviral activity of ARB 001467 for up to 72 weeks after the first dose of study treatment.

  Up to 18 months

Study Arms (4)

0.2 mg/kg ARB-001467 or Placebo

EXPERIMENTAL

HBeAg-negative subjects randomized 3:1 to receive ARB-001467 at 0.2 mg/kg versus placebo once a month for 3 months

Drug: ARB-001467; Other: Placebo

0.4 mg/kg ARB-001467 or Placebo

EXPERIMENTAL

HBeAg-negative subjects randomized 3:1 to receive ARB-001467 at 0.4 mg/kg versus placebo once a month for 3 months

Drug: ARB-001467; Other: Placebo

ARB-001467 or Placebo

EXPERIMENTAL

HBeAg-positive subjects randomized 3:1 to receive ARB-001467 at 0.4 mg/kg versus placebo once a month for 3 months

Drug: ARB-001467; Other: Placebo

0.4 mg/kg ARB-001467

EXPERIMENTAL

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

Drug: ARB-001467

Interventions

ARB-001467 DRUG

An IV infusion of ARB-001467

0.2 mg/kg ARB-001467 or Placebo; 0.4 mg/kg ARB-001467; 0.4 mg/kg ARB-001467 or Placebo; ARB-001467 or Placebo

Placebo OTHER

An IV infusion of placebo

Also known as: 0.9% sodium chloride

0.2 mg/kg ARB-001467 or Placebo; 0.4 mg/kg ARB-001467 or Placebo; ARB-001467 or Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Arbutus Biopharma Corporation: lead

Study Sites (4)

Monash Health, Gastroenterology and Hepatology

Clayton, Victoria, 3168, Australia

Location

The Alfred, Gastroenterology and Hepatology

Melbourne, Victoria, 3004, Australia

Location

Linear Clinical Research Ltd

Nedlands, Western Australia, 6009, Australia

Location

Auckland Clinical Studies Ltd

Auckland, 1010, New Zealand

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Patricia Mendez, MD, PhD

  Arbutus Biopharma Corporation

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Single Blind (Subject) in cohort 1-3, Open label in Cohort 4
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2015
• First Posted: December 15, 2015
• Study Start: December 1, 2015
• Primary Completion: May 18, 2018
• Study Completion: May 18, 2018
• Last Updated: June 29, 2018

Record last verified: 2018-06

Locations

NZ (1); AU (3)