Phase 1b/2a Study of ABI-H0731 in Patients With Chronic Hepatitis B

Study Overview
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Brief Summary
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The purpose of this protocol is to obtain pharmacodynamic and pharmacokinetic data on ABI-H0731 and to provide the opportunity for preliminary evaluation of combination therapy of ABI-H0731 with currently approved antiviral treatment for chronic hepatitis B.

Detailed Description
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The Phase 1b/2a assessments of the dose-related safety, PK, and initial antiviral efficacy of ABI-H0731 in hepatitis B patients will be conducted at approximately 17 different sites to meet enrollment goals of 108 chronic hepatitis B patients.

Official Title
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A Phase 1b/2a, Dose-Ranging Study of the Safety, Tolerability, Pharmacokinetics, and Initial Efficacy of ABI-H0731 in 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 to 65 years of age Chronic HBV infection Body Mass Index (BMI) 18-38 kg/m2 and a minimum body weight of 45 kg Exclusion Criteria: Seropositive for HIV, HCV, or HDV antibody at Screen Previous treatment with any investigational HBV antiviral treatments within the last 6 months Other known cause of liver disease, including NASH Other medical condition that requires persistent medical management or chronic or recurrent pharmacologic or surgical intervention

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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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort B1<br>ABI-H0731 or Placebo in varying doses by mouth for 28 days | Drug: ABI-H0731<br>* A novel HBV core protein allosteric modifier (CpAM) which is being developed as a potential therapeutic advance for CHB patients<br>Drug: Placebo for ABI-H0731<br>* Sugar pill manufactured to mimic the ABI-H0731 tablet<br>|
| Experimental: Cohort B2<br>ABI-H0731 or Placebo in varying doses by mouth for 28 days | Drug: ABI-H0731<br>* A novel HBV core protein allosteric modifier (CpAM) which is being developed as a potential therapeutic advance for CHB patients<br>Drug: Placebo for ABI-H0731<br>* Sugar pill manufactured to mimic the ABI-H0731 tablet<br>|
| Experimental: Cohort B3<br>ABI-H0731 or Placebo in varying doses by mouth for 28 days | Drug: ABI-H0731<br>* A novel HBV core protein allosteric modifier (CpAM) which is being developed as a potential therapeutic advance for CHB patients<br>Drug: Placebo for ABI-H0731<br>* Sugar pill manufactured to mimic the ABI-H0731 tablet<br>|
| Experimental: Cohort B4<br>ABI-H0731 or Placebo in varying doses by mouth for 28 days | Drug: ABI-H0731<br>* A novel HBV core protein allosteric modifier (CpAM) which is being developed as a potential therapeutic advance for CHB patients<br>Drug: Placebo for ABI-H0731<br>* Sugar pill manufactured to mimic the ABI-H0731 tablet<br>|
| Experimental: Cohort B5<br>ABI-H0731 or Placebo in combination with entecavir or tenofovir for 28 days | Drug: ABI-H0731<br>* A novel HBV core protein allosteric modifier (CpAM) which is being developed as a potential therapeutic advance for CHB patients<br>Drug: Placebo for ABI-H0731<br>* Sugar pill manufactured to mimic the ABI-H0731 tablet<br>Drug: Entecavir<br>* An antiviral medication used in the treatment of hepatitis B virus infection<br>* Other names: ETV;Drug: Tenofovir Disoproxil Fumarate<br>* An antiviral medication used in the treatment of hepatitis B virus infection<br>* Other names: TDF;|
| Experimental: Cohort B6<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>* A novel HBV core protein allosteric modifier (CpAM) which is being developed as a potential therapeutic advance for CHB patients<br>Drug: Placebo for ABI-H0731<br>* Sugar pill manufactured to mimic the ABI-H0731 tablet<br>Drug: Pegasys<br>* Used to treat adults with chronic hepatitis B virus who show signs of liver damage<br>* Other names: peginterferon alfa-2a;|

What is the study measuring?
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Primary Outcome Measures

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