Safety, Tolerability, and Pharmacokinetics of AB-836 in Healthy Subjects and Subjects With Chronic HBV Infection
- Conditions
- Chronic Hepatitis
- Interventions
- Registration Number
- NCT04775797
- Lead Sponsor
- Arbutus Biopharma Corporation
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 110
-
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
-
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohorts F-H Placebo Participants in Cohorts F, G, and H will receive multiple doses of AB-836/placebo once daily for 28 days. Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohorts F-H AB-836 Participants in Cohorts F, G, and H will receive multiple doses of AB-836/placebo once daily for 28 days. Part 1 (Healthy Subjects): Single Ascending Dose (SAD) Placebo 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. Part 2a (Healthy Subjects): Multiple Ascending Dose (MAD) AB-836 Participants in Cohorts C, D and E will receive a once daily dose of AB-836/placebo for 10 days Part 2a (Healthy Subjects): Multiple Ascending Dose (MAD) Placebo Participants in Cohorts C, D and E will receive a once daily dose of AB-836/placebo for 10 days Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohort I AB-836 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. Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohort I Placebo 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. Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohort I Nucleos(t)ide Analogue 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. Part 2b (Healthy Subjects): MAD AB-836 Participants in Cohorts J will receive a once daily dose of AB-836/placebo for 35 days Part 2b (Healthy Subjects): MAD Placebo Participants in Cohorts J will receive a once daily dose of AB-836/placebo for 35 days Part 1 (Healthy Subjects): Single Ascending Dose (SAD) AB-836 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.
- Primary Outcome Measures
Name Time Method 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
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (15)
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Ottawa Hospital Research Institute
🇨🇦Ottawa, Ontario, Canada
Toronto Liver Center
🇨🇦Toronto, Ontario, Canada
Nepean Hospital
🇦🇺Kingswood, New South Wales, Australia
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Arensia Exploratory Medicine
🇲🇩Chisinau, Moldova, Republic of
Hospital For Tropical Diseases
🇹🇭Bangkok, Thailand
New Zealand Clinical Research Auckland
🇳🇿Auckland, New Zealand
Srinagarind Hospital
🇹🇭Khon Kaen, Thailand
Medical Center of Limited Liability Company Arensia Exploratory Medicine
🇺🇦Kyiv, Ukraine
King Chulalongkorn Memorial Hospital
🇹🇭Bangkok, Thailand
Naresuan University Hospital
🇹🇭Phitsanulok, Thailand
Maharaj Nakorn Chiang Mai Hospital
🇹🇭Chiang Mai, Thailand
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong