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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Chronic Hepatitis

Intervention / Treatment
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* Drug: AB-836
* Drug: Placebo
* Drug: AB-836
* Drug: Placebo
* Drug: Nucleos(t)ide Analogue


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |