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

Chronic Hepatitis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04775797
• Other study ID #: AB-836-001
• Status: Terminated
• Phase: Phase 1
• Start date: June 25, 2021
• Est. completion date: November 17, 2022

Study information

• Verified date: November 2022
• Source: Arbutus Biopharma Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 110
• Est. completion date: November 17, 2022
• Est. primary completion date: November 17, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Hepatitis
• Hepatitis, Chronic

Intervention

Drug:
• AB-836
Capsules or Tablets
• Placebo
Capsules of Tablets
• AB-836
Tablets
• Placebo
Tablets
• Nucleos(t)ide Analogue
Tablets

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Nepean Hospital	Kingswood	New South Wales
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Toronto Liver Center	Toronto	Ontario
Hong Kong	Queen Mary Hospital	Hong Kong
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Asan Medical Center	Seoul
Moldova, Republic of	Arensia Exploratory Medicine	Chisinau
New Zealand	New Zealand Clinical Research Auckland	Auckland
Thailand	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
Ukraine	Medical Center of Limited Liability Company Arensia Exploratory Medicine	Kyiv

Sponsors (1)

Lead Sponsor	Collaborator
Arbutus Biopharma Corporation

Countries where clinical trial is conducted

Australia,  Canada,  Hong Kong,  Korea, Republic of,  Moldova, Republic of,  New Zealand,  Thailand,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of TEAEs		Up to 35 days after last dose of AB-836/placebo
Primary	Incidence of discontinuations due to AEs		Up to 35 days after last dose of AB-836/placebo
Primary	Incidence of lab abnormalities		Up to 35 days after last dose of AB-836/placebo