A Study in Healthy Volunteers and Patients With Chronic Hepatitis B

Study Overview
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Brief Summary
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This two-part, Phase 1 protocol will be the first clinical study of ABI-H0731. Part I will be a Phase 1a dose-ranging assessment of ABI-H0731 in healthy adult volunteers. If the dose-related safety, tolerability and pharmacokinetics (PK) of ABI-H0731 in human volunteers are deemed satisfactory, then the study will advance to Part II, a Phase 1b dose-ranging assessment of ABI-H0731 in non-cirrhotic, CHB patients.

Official Title
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A Phase 1a/1b, Dose-Ranging Study of the Safety, Tolerability, Pharmacokinetics, and Initial Efficacy of ABI-H0731 in Healthy Volunteers and Patients With Chronic Hepatitis B

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: ABI-H0731
* Drug: Placebo for ABI-H0731
* Drug: Entecavir
* Drug: Tenofovir disoproxil fumarate
* Drug: Pegasys
* Drug: Nucleos(t)ide


Participation Criteria
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Eligibility Criteria
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Healthy volunteers: Male or female between 18 and 65 years old with a BMI of 18-32kg/m2 Must be in good health and not have any health condition which could interfere with the absorption, distribution or elimination of study drug, or with the clinical and laboratory assessments in this study CHB patients: Male or female between 18 and 65 years of age, with a BMI of 18-35kg/m2 and a minimum body weight of 45 kg Must have chronic hepatitis B with no history of clinical decompensation Seropositive for HIV, HCV, or HDV antibody at Screen Previous treatment with any HBV antiviral treatments within the last 3 months Other known cause of liver disease, including NASH

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABI-H0731 or Matching Placebo<br>ABI-H0731 in varying doses of tablets by mouth for 1 day, 7 days, or 28 days | Drug: ABI-H0731<br> <br> Drug: Placebo for ABI-H0731<br> <br> * Other names: Sugar pill manufactured to mimic the ABI-H0731 tablet;|
| Experimental: ABI-H0731 or Placebo and ETV or TDF<br>ABI-H0731 and entecavir or tenofovir in combination in a yet to be determined dose by mouth for 28 days | Drug: ABI-H0731<br> <br> Drug: Placebo for ABI-H0731<br> <br> * Other names: Sugar pill manufactured to mimic the ABI-H0731 tablet;Drug: Entecavir<br>* Used to treat adults with chronic hepatitis B virus<br>Drug: Tenofovir disoproxil fumarate<br>* Used to treat adults with chronic hepatitis B virus<br>|
| Experimental: ABI-H0731 or Placebo and a Nucleos(t)ide and Pegasys<br>ABI-H0731 or Placebo, in combination with a commerically-approved nucleos(t)ide plus PegIFN in treatment-experienced patients, for 28 days | Drug: ABI-H0731<br> <br> Drug: Placebo for ABI-H0731<br> <br> * Other names: Sugar pill manufactured to mimic the ABI-H0731 tablet;Drug: Pegasys<br>* Used to treat adults with chronic hepatitis B virus who show signs of liver damage<br>* Other names: peginterferon alfa-2a;Drug: Nucleos(t)ide<br>* Used to treat adults with chronic hepatitis B virus<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of healthy volunteers and patients with chronic HBV infection with treatment-related adverse events as assessed by CTCAE v4.0. |  | Up to 57 days |