Safety, Tolerability, PK & PD of AB-101 Following Oral Administration in Healthy and CHB Subjects.

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-101. Parts 1 and 2 will be a Phase 1a SAD/MAD of AB-101 in healthy adult subjects. Part 3 will be a Phase 1b dose-ranging assessment of AB-101 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, PK and PD of AB-101, an Oral PD-L1 Inhibitor, in Healthy Subjects and Subjects With Chronic HBV Infection.

Conditions
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Chronic Hepatitis b

Intervention / Treatment
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* Drug: AB-101
* Drug: Placebo
* Drug: Nucleos(t)ide Analogue


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part 1 and 2 (Healthy Volunteers) Male between ages 18-50 years Willing and able to provide informed consent Willing to follow protocol-specified contraception requirement Inclusion Criteria: Part 3 (CHB Subjects) Male or female subjects between the ages of 18-60 years Willing to provide informed consent Chronic HBV infection for at least 6 months Willing to follow protocol-specified contraception requirement Exclusion Criteria: Part 1 and 2 (Healthy Volunteers) Key Exclusion Criteria: Clinically significant lab abnormalities A history of clinically significant gastrointestinal, hematologic, renal, hepatic, bronchopulmonary, neurological, psychiatric, cardiovascular, autoimmune or other immune-mediated disease. HIV or Hep C positive Known chronic or severe infection or recent significant exposure to infections such as tuberculosis or endemic mycosis, untreated latent infections like tuberculosis, or a positive or indeterminate QuantiFERON test. Exclusion Criteria: Part 3 (CHB Subjects) Have extensive fibrosis or cirrhosis of the liver Have or had liver cancer (hepatocellular carcinoma) Have a history or current autoimmune disease or has been on immunosuppressive medications within 6 months of the start of the study Females who breastfeeding, pregnant or who wish to become pregnant during the study Known chronic or severe infection or recent significant exposure to infections such as tuberculosis or endemic mycosis, untreated latent infections like tuberculosis, or a positive or indeterminate QuantiFERON test.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br> | Drug: AB-101<br>* AB-101 is an oral small molecule PD-L1 checkpoint inhibitor being developed for the treatment of chronic infection with HBV in combination with other agents.<br>Drug: Placebo<br>* A placebo is any treatment that has no active properties, such as a sugar pill. We will use matching placebo for this study.<br>|
| Experimental: Part 2<br> | Drug: AB-101<br>* AB-101 is an oral small molecule PD-L1 checkpoint inhibitor being developed for the treatment of chronic infection with HBV in combination with other agents.<br>Drug: Placebo<br>* A placebo is any treatment that has no active properties, such as a sugar pill. We will use matching placebo for this study.<br>|
| Experimental: Part 3<br> | Drug: AB-101<br>* AB-101 is an oral small molecule PD-L1 checkpoint inhibitor being developed for the treatment of chronic infection with HBV in combination with other agents.<br>Drug: Placebo<br>* A placebo is any treatment that has no active properties, such as a sugar pill. We will use matching placebo for this study.<br>Drug: Nucleos(t)ide Analogue<br>* Nucleos(t)ide analogues (NUCs) are the standard and mostly lifelong treatment for chronic HBeAg-negative hepatitis B.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts 1 and 2: Incidence of adverse events (AEs), serious AEs (SAEs), immune related AEs (irAEs) and discontinuations due to AEs and irAEs. |  | [Time Frame: Up to 57 (Part 1) or 84 (Part 2) days] | 
| Part 3: Incidence of AEs, SAEs, irAEs and discontinuations due to AEs and irAEs |  | [Time Frame: Up to 196 days] | 
| Parts 1 and 2: Incidence of clinically significant laboratory abnormalities Parts 1 and 2: Incidence of clinically significant laboratory abnormalities |  | [Time Frame: Up to 57 (Part 1) or 84 (Part 2) days] | 
| Parts 1 and 2: Incidence of clinically significant changes in vital signs (heart rate, blood pressure, temperature, respiratory rate), physical examinations and electrocardiograms (ECGs) |  | [Time Frame: Up to 57 (Part 1) or 84 (Part 2) days] | 
| Part 3: Incidence of clinically significant laboratory abnormalities |  | [Time Frame: Up to 196 days] | 
| Part 3: Incidence of clinically significant changes in vital signs (heart rate, blood pressure, temperature, respiratory rate), physical examinations and electrocardiograms (ECGs) |  | [Time Frame: Up to 196 days] |