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

Primary Purpose

Hepatitis B, Chronic

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ARB-001467
Placebo
Sponsored by
Arbutus Biopharma Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B, Chronic

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Monash Health, Gastroenterology and Hepatology
  • The Alfred, Gastroenterology and Hepatology
  • Linear Clinical Research Ltd
  • Auckland Clinical Studies Ltd

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

0.2 mg/kg ARB-001467 or Placebo

0.4 mg/kg ARB-001467 or Placebo

ARB-001467 or Placebo

0.4 mg/kg ARB-001467

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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).
To evaluate the pharmacokinetics of multiple doses of ARB-001467 in subjects with chronic HBV infection.
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).
To evaluate the pharmacokinetics of multiple doses of ARB-001467 in subjects with chronic HBV infection.
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).
To evaluate the pharmacokinetics of multiple doses of ARB-001467 in subjects with chronic HBV infection.
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.
To evaluate the pharmacokinetics of multiple doses of ARB-001467 in subjects with chronic HBV infection.
Evaluate antiviral activity of ARB 001467 for up to 72 weeks after the first dose of study treatment.
The proportion of subjects in each dose level cohort with ≥0.5 log10 HBsAg decrease from baseline at EOS, and for these subjects, the changes from baseline (expressed as percentage and log10 change) in the following virologic markers will be assessed throughout the study: Quantitative HBV surface antigen (HBsAg) Quantitative HBV surface antibody (HBsAb) Quantitative HBV DNA and HBV-RNA (viral load) For the HBeAg positive cohort only: - Quantitative HBV e antigen (HBeAg)

Full Information

First Posted
December 7, 2015
Last Updated
June 28, 2018
Sponsor
Arbutus Biopharma Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT02631096
Brief Title
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

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
December 2015 (undefined)
Primary Completion Date
May 18, 2018 (Actual)
Study Completion Date
May 18, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arbutus Biopharma Corporation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Masking Description
Single Blind (Subject) in cohort 1-3, Open label in Cohort 4
Allocation
Randomized
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
0.2 mg/kg ARB-001467 or Placebo
Arm Type
Experimental
Arm Description
HBeAg-negative subjects randomized 3:1 to receive ARB-001467 at 0.2 mg/kg versus placebo once a month for 3 months
Arm Title
0.4 mg/kg ARB-001467 or Placebo
Arm Type
Experimental
Arm Description
HBeAg-negative subjects randomized 3:1 to receive ARB-001467 at 0.4 mg/kg versus placebo once a month for 3 months
Arm Title
ARB-001467 or Placebo
Arm Type
Experimental
Arm Description
HBeAg-positive subjects randomized 3:1 to receive ARB-001467 at 0.4 mg/kg versus placebo once a month for 3 months
Arm Title
0.4 mg/kg ARB-001467
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
ARB-001467
Intervention Description
An IV infusion of ARB-001467
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
0.9% sodium chloride
Intervention Description
An IV infusion of placebo
Primary Outcome Measure Information:
Title
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.
Description
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
Time Frame
28 days post last infusion
Secondary Outcome Measure Information:
Title
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).
Description
To evaluate the pharmacokinetics of multiple doses of ARB-001467 in subjects with chronic HBV infection.
Time Frame
Up to 36 Weeks
Title
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).
Description
To evaluate the pharmacokinetics of multiple doses of ARB-001467 in subjects with chronic HBV infection.
Time Frame
Up to 36 Weeks
Title
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).
Description
To evaluate the pharmacokinetics of multiple doses of ARB-001467 in subjects with chronic HBV infection.
Time Frame
Up to 36 Weeks
Title
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.
Description
To evaluate the pharmacokinetics of multiple doses of ARB-001467 in subjects with chronic HBV infection.
Time Frame
Up to 36 Weeks
Title
Evaluate antiviral activity of ARB 001467 for up to 72 weeks after the first dose of study treatment.
Description
The proportion of subjects in each dose level cohort with ≥0.5 log10 HBsAg decrease from baseline at EOS, and for these subjects, the changes from baseline (expressed as percentage and log10 change) in the following virologic markers will be assessed throughout the study: Quantitative HBV surface antigen (HBsAg) Quantitative HBV surface antibody (HBsAb) Quantitative HBV DNA and HBV-RNA (viral load) For the HBeAg positive cohort only: - Quantitative HBV e antigen (HBeAg)
Time Frame
Up to 18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patricia Mendez, MD, PhD
Organizational Affiliation
Arbutus Biopharma Corporation
Official's Role
Study Chair
Facility Information:
Facility Name
Monash Health, Gastroenterology and Hepatology
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
The Alfred, Gastroenterology and Hepatology
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Linear Clinical Research Ltd
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Auckland Clinical Studies Ltd
City
Auckland
ZIP/Postal Code
1010
Country
New Zealand

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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