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Safety, Tolerability, and Pharmacokinetics of AB-836 in Healthy Subjects and Subjects With Chronic HBV Infection

Primary Purpose

Chronic Hepatitis

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AB-836
Placebo
AB-836
Placebo
Nucleos(t)ide Analogue
Sponsored by
Arbutus Biopharma Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy Subjects

    1. Male and Female (not of childbearing potential in Part 1 and 2a) subjects between 18 and 45 years old
    2. Free from clinically significant illness or disease as determined by their medical history, physical examination, vital signs, and clinical laboratory test results.
    3. BMI of 18-32 kg/m2.

  • CHB Subjects:

    1. Male or female between 18 and 65 years old.
    2. Chronic HBV infection documented as a positive HBsAg, HBV DNA, or HBeAg test at least 6 months prior to the Screening Visit, or a historical liver biopsy consistent with chronic HBV infection

    3. For cohort F, G, H:

      1. HBV DNA ≥2,000 IU/mL at Screening (subjects may be either treatment-naïve or treatment-experienced but currently off-treatment).
      2. ALT ≤ 5x ULN

    4. For Cohort I:

      1. HBV DNA <LLOQ at Screening
      2. Subjects must have been receiving either TAF, TDF, or ETV consistently for ≥6 months prior to Day 1 and are willing to continue with the same NA treatment through the final study visit.
      3. ALT ≤ 2.5 x ULN
    5. HbsAg ≥250 IU/mL at screening

Exclusion Criteria:

  • CHB Subjects

    1. Advanced fibrosis, cirrhosis or other signs of advanced liver disease as assessed by clinical history, ultrasound or FibroScan, or history of cirrhosis or any clinically significant medical condition associated with chronic liver disease.
    2. Co-infection with HIV or other non-B hepatitis viruses.
    3. Any clinically significant or unstable medical condition or illness that could confound study findings.
    4. Subjects who are unwilling to comply with protocol contraception requirements, and female subjects who are pregnant or breastfeeding.
    5. Previous treatment with a capsid inhibitor, core inhibitor, or core protein assembly modifier [CpAM or CAM]) within 6 months of the Day 1 visit, or prior treatment with an HBV-targeted siRNA or antisense oligonucleotide compound at any time.

Sites / Locations

  • Royal Prince Alfred Hospital
  • Nepean Hospital
  • Ottawa Hospital Research Institute
  • Toronto Liver Center
  • Queen Mary Hospital
  • Pusan National University Hospital
  • Asan Medical Center
  • Arensia Exploratory Medicine
  • New Zealand Clinical Research Auckland
  • Hospital For Tropical Diseases
  • King Chulalongkorn Memorial Hospital
  • Maharaj Nakorn Chiang Mai Hospital
  • Srinagarind Hospital
  • Naresuan University Hospital
  • Medical Center of Limited Liability Company Arensia Exploratory Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Part 1 (Healthy Subjects): Single Ascending Dose (SAD)

Part 2a (Healthy Subjects): Multiple Ascending Dose (MAD)

Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohorts F-H

Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohort I

Part 2b (Healthy Subjects): MAD

Arm Description

Two cohorts (Cohorts A and B) of healthy subjects will receive single doses of AB-836/placebo in an alternating cohort design under fasted conditions. One additional treatment will be administered under fed conditions.

Participants in Cohorts C, D and E will receive a once daily dose of AB-836/placebo for 10 days

Participants in Cohorts F, G, and H will receive multiple doses of AB-836/placebo once daily for 28 days.

Participants in Cohort I will receive multiple doses of AB-836/placebo once daily for 28 days in combination with ongoing nucleos(t)ide analog (NA) therapy.

Participants in Cohorts J will receive a once daily dose of AB-836/placebo for 35 days

Outcomes

Primary Outcome Measures

Incidence of TEAEs
Incidence of discontinuations due to AEs
Incidence of lab abnormalities

Secondary Outcome Measures

Full Information

First Posted
February 24, 2021
Last Updated
November 17, 2022
Sponsor
Arbutus Biopharma Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT04775797
Brief Title
Safety, Tolerability, and Pharmacokinetics of AB-836 in Healthy Subjects and Subjects With Chronic HBV Infection
Official Title
A Double-Blind, Randomized, Placebo-Controlled, Single and Multiple Dose Study Evaluating the Safety, Tolerability, and Pharmacokinetics of AB-836, an HBV Capsid Inhibitor, in Healthy Subjects and Subjects With Chronic HBV Infection
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Terminated
Why Stopped
Safety
Study Start Date
June 25, 2021 (Actual)
Primary Completion Date
November 17, 2022 (Actual)
Study Completion Date
November 17, 2022 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This three-part, Phase 1 protocol will be the first clinical study of AB-836. Parts 1 and 2a/b will be a Phase 1a SAD/MAD of AB-836 in healthy adult subjects. Part 3 will be a Phase 1b dose-ranging assessment of AB-836 in non-cirrhotic Chronic Hepatitis B (CHB) subjects.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
Single blind only (Participant) in Part 2b
Allocation
Randomized
Enrollment
110 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1 (Healthy Subjects): Single Ascending Dose (SAD)
Arm Type
Experimental
Arm Description
Two cohorts (Cohorts A and B) of healthy subjects will receive single doses of AB-836/placebo in an alternating cohort design under fasted conditions. One additional treatment will be administered under fed conditions.
Arm Title
Part 2a (Healthy Subjects): Multiple Ascending Dose (MAD)
Arm Type
Experimental
Arm Description
Participants in Cohorts C, D and E will receive a once daily dose of AB-836/placebo for 10 days
Arm Title
Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohorts F-H
Arm Type
Experimental
Arm Description
Participants in Cohorts F, G, and H will receive multiple doses of AB-836/placebo once daily for 28 days.
Arm Title
Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohort I
Arm Type
Experimental
Arm Description
Participants in Cohort I will receive multiple doses of AB-836/placebo once daily for 28 days in combination with ongoing nucleos(t)ide analog (NA) therapy.
Arm Title
Part 2b (Healthy Subjects): MAD
Arm Type
Experimental
Arm Description
Participants in Cohorts J will receive a once daily dose of AB-836/placebo for 35 days
Intervention Type
Drug
Intervention Name(s)
AB-836
Intervention Description
Capsules or Tablets
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Capsules of Tablets
Intervention Type
Drug
Intervention Name(s)
AB-836
Intervention Description
Tablets
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Tablets
Intervention Type
Drug
Intervention Name(s)
Nucleos(t)ide Analogue
Intervention Description
Tablets
Primary Outcome Measure Information:
Title
Incidence of TEAEs
Time Frame
Up to 35 days after last dose of AB-836/placebo
Title
Incidence of discontinuations due to AEs
Time Frame
Up to 35 days after last dose of AB-836/placebo
Title
Incidence of lab abnormalities
Time Frame
Up to 35 days after last dose of AB-836/placebo

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy Subjects Male and Female (not of childbearing potential in Part 1 and 2a) subjects between 18 and 45 years old Free from clinically significant illness or disease as determined by their medical history, physical examination, vital signs, and clinical laboratory test results. BMI of 18-32 kg/m2. CHB Subjects: Male or female between 18 and 65 years old. Chronic HBV infection documented as a positive HBsAg, HBV DNA, or HBeAg test at least 6 months prior to the Screening Visit, or a historical liver biopsy consistent with chronic HBV infection For cohort F, G, H: HBV DNA ≥2,000 IU/mL at Screening (subjects may be either treatment-naïve or treatment-experienced but currently off-treatment). ALT ≤ 5x ULN For Cohort I: HBV DNA <LLOQ at Screening Subjects must have been receiving either TAF, TDF, or ETV consistently for ≥6 months prior to Day 1 and are willing to continue with the same NA treatment through the final study visit. ALT ≤ 2.5 x ULN HbsAg ≥250 IU/mL at screening Exclusion Criteria: CHB Subjects Advanced fibrosis, cirrhosis or other signs of advanced liver disease as assessed by clinical history, ultrasound or FibroScan, or history of cirrhosis or any clinically significant medical condition associated with chronic liver disease. Co-infection with HIV or other non-B hepatitis viruses. Any clinically significant or unstable medical condition or illness that could confound study findings. Subjects who are unwilling to comply with protocol contraception requirements, and female subjects who are pregnant or breastfeeding. Previous treatment with a capsid inhibitor, core inhibitor, or core protein assembly modifier [CpAM or CAM]) within 6 months of the Day 1 visit, or prior treatment with an HBV-targeted siRNA or antisense oligonucleotide compound at any time.
Facility Information:
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Wales
Country
Australia
Facility Name
Nepean Hospital
City
Kingswood
State/Province
New South Wales
Country
Australia
Facility Name
Ottawa Hospital Research Institute
City
Ottawa
State/Province
Ontario
Country
Canada
Facility Name
Toronto Liver Center
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Pusan National University Hospital
City
Busan
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
Country
Korea, Republic of
Facility Name
Arensia Exploratory Medicine
City
Chisinau
Country
Moldova, Republic of
Facility Name
New Zealand Clinical Research Auckland
City
Auckland
Country
New Zealand
Facility Name
Hospital For Tropical Diseases
City
Bangkok
Country
Thailand
Facility Name
King Chulalongkorn Memorial Hospital
City
Bangkok
Country
Thailand
Facility Name
Maharaj Nakorn Chiang Mai Hospital
City
Chiang Mai
Country
Thailand
Facility Name
Srinagarind Hospital
City
Khon Kaen
Country
Thailand
Facility Name
Naresuan University Hospital
City
Phitsanulok
Country
Thailand
Facility Name
Medical Center of Limited Liability Company Arensia Exploratory Medicine
City
Kyiv
Country
Ukraine

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Safety, Tolerability, and Pharmacokinetics of AB-836 in Healthy Subjects and Subjects With Chronic HBV Infection

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