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

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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Hepatitis
• Intervention / Treatment: Drug: Placebo; Drug: AB-836; Drug: Placebo; Drug: AB-836; Drug: Nucleos(t)ide Analogue

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia
      • Royal Prince Alfred Hospital
    • Kingswood, New South Wales, Australia
      • Nepean Hospital
• Canada
  • Ontario
    • Ottawa, Ontario, Canada
      • Ottawa Hospital Research Institute
    • Toronto, Ontario, Canada
      • Toronto Liver Center
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
• Korea, Republic of
  • Busan, Korea, Republic of
    • Pusan National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
    • Arensia Exploratory Medicine
• New Zealand
  • Auckland, New Zealand
    • New Zealand Clinical Research Auckland
• Thailand
  • Bangkok, Thailand
    • King Chulalongkorn Memorial Hospital
  • Bangkok, Thailand
    • Hospital for Tropical Diseases
  • Chiang Mai, Thailand
    • Maharaj Nakorn Chiang Mai Hospital
  • Khon Kaen, Thailand
    • Srinagarind Hospital
  • Phitsanulok, Thailand
    • Naresuan University Hospital
• Ukraine
  • Kyiv, Ukraine
    • Medical Center of Limited Liability Company Arensia Exploratory Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 (Healthy Subjects): Single Ascending Dose (SAD); 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.	Drug: Placebo; Tablets; Drug: AB-836; Capsules or Tablets; Drug: Placebo; Capsules of Tablets; Drug: AB-836; Tablets
Experimental: Part 2a (Healthy Subjects): Multiple Ascending Dose (MAD); Participants in Cohorts C, D and E will receive a once daily dose of AB-836/placebo for 10 days	Drug: Placebo; Tablets; Drug: AB-836; Capsules or Tablets; Drug: Placebo; Capsules of Tablets; Drug: AB-836; Tablets
Experimental: Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohorts F-H; Participants in Cohorts F, G, and H will receive multiple doses of AB-836/placebo once daily for 28 days.	Drug: Placebo; Tablets; Drug: AB-836; Capsules or Tablets; Drug: Placebo; Capsules of Tablets; Drug: AB-836; Tablets
Experimental: Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohort I; 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.	Drug: Placebo; Tablets; Drug: AB-836; Capsules or Tablets; Drug: Placebo; Capsules of Tablets; Drug: AB-836; Tablets; Drug: Nucleos(t)ide Analogue; Tablets
Experimental: Part 2b (Healthy Subjects): MAD; Participants in Cohorts J will receive a once daily dose of AB-836/placebo for 35 days	Drug: Placebo; Tablets; Drug: AB-836; Capsules or Tablets; Drug: Placebo; Capsules of Tablets; Drug: AB-836; Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of TEAEs	Up to 35 days after last dose of AB-836/placebo
Incidence of discontinuations due to AEs	Up to 35 days after last dose of AB-836/placebo
Incidence of lab abnormalities	Up to 35 days after last dose of AB-836/placebo

Collaborators and Investigators

• Sponsor: Arbutus Biopharma Corporation

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2021
• Primary Completion (Actual): November 17, 2022
• Study Completion (Actual): November 17, 2022

Study Registration Dates

• First Submitted: February 24, 2021
• First Submitted That Met QC Criteria: February 26, 2021
• First Posted (Actual): March 1, 2021

Study Record Updates

• Last Update Posted (Actual): November 21, 2022
• Last Update Submitted That Met QC Criteria: November 17, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Hepatitis; Hepatitis, Chronic
• Other Study ID Numbers: AB-836-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No