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

NCT04775797 | Terminated Phase 1 DMC

• 1 other identifier: AB-836-001
• Study Type: interventional
• Target: 110
• Locations: 8 countries
• Sites: 15

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

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (5)

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

EXPERIMENTAL

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: AB-836; Drug: Placebo

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

EXPERIMENTAL

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

Drug: AB-836; Drug: Placebo

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

EXPERIMENTAL

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

Drug: AB-836; Drug: Placebo

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

EXPERIMENTAL

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: AB-836; Drug: Placebo; Drug: Nucleos(t)ide Analogue

Part 2b (Healthy Subjects): MAD

EXPERIMENTAL

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

Drug: AB-836; Drug: Placebo

Interventions

AB-836 DRUG

Capsules or Tablets

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

Placebo DRUG

Capsules of Tablets

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

Nucleos(t)ide Analogue DRUG

Tablets

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

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Arbutus Biopharma Corporation: lead

Study Sites (15)

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Location

Nepean Hospital

Kingswood, New South Wales, Australia

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Location

Toronto Liver Center

Toronto, Ontario, Canada

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Arensia Exploratory Medicine

Chisinau, Moldova

Location

New Zealand Clinical Research Auckland

Auckland, New Zealand

Location

Pusan National University Hospital

Busan, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Hospital For Tropical Diseases

Bangkok, Thailand

Location

King Chulalongkorn Memorial Hospital

Bangkok, Thailand

Location

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, Thailand

Location

Srinagarind Hospital

Khon Kaen, Thailand

Location

Naresuan University Hospital

Phitsanulok, Thailand

Location

Medical Center of Limited Liability Company Arensia Exploratory Medicine

Kyiv, Ukraine

Location

MeSH Terms

Conditions

Hepatitis, Chronic

Condition Hierarchy (Ancestors)

Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Single blind only (Participant) in Part 2b
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2021
• First Posted: March 1, 2021
• Study Start: June 25, 2021
• Primary Completion: November 17, 2022
• Study Completion: November 17, 2022
• Last Updated: November 21, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

TH (5); HK (1); MO (1); NZ (1); UA (1); KR (2); AU (2); CA (2)