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

NCT ID: NCT04775797

Last Updated: 2022-11-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-25
• Study Completion Date: 2022-11-17

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.

Conditions

Chronic Hepatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

AB-836

Intervention Type: DRUG

Capsules or Tablets

Placebo

Intervention Type: DRUG

Capsules of Tablets

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

Group Type: EXPERIMENTAL

AB-836

Intervention Type: DRUG

Tablets

Placebo

Intervention Type: DRUG

Tablets

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.

Group Type: EXPERIMENTAL

AB-836

Intervention Type: DRUG

Tablets

Placebo

Intervention Type: DRUG

Tablets

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.

Group Type: EXPERIMENTAL

AB-836

Intervention Type: DRUG

Tablets

Placebo

Intervention Type: DRUG

Tablets

Nucleos(t)ide Analogue

Intervention Type: DRUG

Tablets

Part 2b (Healthy Subjects): MAD

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

Group Type: EXPERIMENTAL

AB-836

Intervention Type: DRUG

Tablets

Placebo

Intervention Type: DRUG

Tablets

Interventions

AB-836

Capsules or Tablets

Intervention Type: DRUG

Placebo

Capsules of Tablets

Intervention Type: DRUG

AB-836

Tablets

Intervention Type: DRUG

Placebo

Tablets

Intervention Type: DRUG

Nucleos(t)ide Analogue

Tablets

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Arbutus Biopharma Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Nepean Hospital

Kingswood, New South Wales, Australia

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Toronto Liver Center

Toronto, Ontario, Canada

Queen Mary Hospital

Hong Kong, , Hong Kong

Arensia Exploratory Medicine

Chisinau, , Moldova

New Zealand Clinical Research Auckland

Auckland, , New Zealand

Pusan National University Hospital

Busan, , South Korea

Asan Medical Center

Seoul, , South Korea

Hospital For Tropical Diseases

Bangkok, , Thailand

King Chulalongkorn Memorial Hospital

Bangkok, , Thailand

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, , Thailand

Srinagarind Hospital

Khon Kaen, , Thailand

Naresuan University Hospital

Phitsanulok, , Thailand

Medical Center of Limited Liability Company Arensia Exploratory Medicine

Kyiv, , Ukraine

Countries

Australia; Canada; Hong Kong; Moldova; New Zealand; South Korea; Thailand; Ukraine

Other Identifiers

AB-836-001

Identifier Type: -

Identifier Source: org_study_id