A Study Evaluating ABI-H0731 as Adjunctive Therapy in Participants With Chronic Hepatitis B Infection

Chronic Hepatitis B Clinical Trial

Official title:

A Phase 2a, Multi-center, Double-blind, Placebo-controlled Study Evaluating ABI-H0731 as Adjunctive Therapy in Virally-suppressed Patients With Chronic Hepatitis B

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03576066
• Other study ID #: ABI-H0731-201
• Status: Completed
• Phase: Phase 2
• Start date: June 11, 2018
• Est. completion date: July 5, 2019

Study information

• Verified date: January 2021
• Source: Assembly Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if ABI-H0731 given in combination with a standard of care (SOC) hepatitis B virus (HBV) nucleos(t)ide reverse transcriptase inhibitor (NUC) medication is safe and effective in participants with chronic hepatitis B virus infection (cHBV).

Description:

This is a Phase 2a, Multi-center, Double-blind, Placebo-controlled Study Evaluating ABI-H0731 as Adjunctive Therapy in Virally-suppressed Participants with cHBV.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: July 5, 2019
• Est. primary completion date: July 5, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Key Inclusion Criteria:

• Male or female between ages 18 and 70 years

• Virologically-suppressed (defined as HBV DNA =limit of quantitation (LOQ) for at least 6 months before screening on SOC NUC therapy

• HBeAg-positive or HBeAg-negative at screening

• In good general health except for cHBV

Key Exclusion Criteria:

• Co-infection with HIV, hepatitis C virus (HCV), hepatitis E virus (HEV) or hepatitis D virus (HDV)

• History or evidence of hepatic decompensation (including gastrointestinal bleeding or esophageal varices) at any time prior to or at time of screening

• Clinically significant cardiac or pulmonary disease, chronic or recurrent renal or urinary tract disease, liver disease other than HBV, endocrine disorder, autoimmune disorder, diabetes mellitus requiring treatment with insulin or hypoglycemic agents, neuromuscular, musculoskeletal, or mucocutaneous conditions requiring frequent treatment, seizure disorders requiring treatment, or other medical conditions requiring frequent medical management or pharmacologic or surgical treatment that in the opinion of the Investigator or the Sponsor makes the participant unsuitable for the study

• Previous treatment with an investigational agent for HBV other than ABI-H0731 in the last 6 months before screening

• History of hepatocellular carcinoma (HCC)

• Females who are lactating or pregnant or wish to become pregnant are excluded from the study

• Exclusionary laboratory parameters at screening include:

• Platelet count <100,000/mm3

• Albumin <lower limit of normal (LLN)

• Direct bilirubin >1.2×upper limit of normal (ULN)

• Alanine aminotransferase (ALT) >5×ULN at screening

• International Normalized Ratio (INR) >1.5×ULN

• Glomerular filtration rate (GFR) <60 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• ABI-H0731
Participants will receive ABI-H0731 300 mg tablets orally once daily (QD).
• SOC NUC
Participants will continue on their SOC NUC (ETV, TDF or TAF) tablet orally as per approved package insert.
• Placebo Oral Tablet
Participants will receive placebo matching ABI-0731 tablets orally QD.

Locations

Country	Name	City	State
Canada	Toronto General Hospital	Toronto
Canada	Toronto Liver Center	Toronto
Canada	GI Research Institute	Vancouver
New Zealand	Auckland City Hospital	Auckland
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Cedars-Sinai Medical Center	Beverly Hills	California
United States	Digestive Disease Associates	Catonsville	Maryland
United States	Southern California Research Center	Coronado	California
United States	Sing Chan, MD	Flushing	New York
United States	Infectious Disease Care	Hillsborough	New Jersey
United States	Asia Pacific Liver Center	Los Angeles	California
United States	University of California Los Angeles	Los Angeles	California
United States	University of Miami Hospital and Clinics	Miami	Florida
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	NYU Langone Health	New York	New York
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Xiaoli Ma, MD	Philadelphia	Pennsylvania
United States	Medical Associates Research Group	San Diego	California
United States	Research and Education	San Diego	California
United States	Quest Clinical Research	San Francisco	California
United States	Stanford University Medical Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Assembly Biosciences

Countries where clinical trial is conducted

United States,  Canada,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Mean log10 Serum HBsAg From Baseline (Day 1) to Week 24 on ABI-H0731 + SOC NUC as Compared to Placebo + SOC NUC		Baseline to Week 24
Primary	Change in Mean log10 Serum HBeAg From Baseline (Day 1) to Week 24 on ABI-H0731 + SOC NUC as Compared to Placebo + SOC NUC		Baseline to Week 24
Secondary	Number of Participants With One or More Adverse Events		Up to Follow-up (maximum up to Week 36)
Secondary	Number of Participants With Premature Study Discontinuation		Up to Follow-up (maximum up to Week 36)
Secondary	Number of Participants With One or More Abnormal Safety Laboratory Result		Up to Week 36
Secondary	Number of Participants With a Clinically-significant Electrocardiogram Abnormality		Up to Week 24
Secondary	Number of Participants With a Clinically-significant Change in Vital Signs	Vital signs assessed were body temperature, respiratory rate, and pulse rate	Baseline and up to Week 24
Secondary	Number of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at Week 24 on ABI-H0731 + NUC Therapy as Compared With Placebo + NUC Therapy	Abnormal ALT was defined as =1.25 x upper limit of normal (34 Units/L for female and 43 Units/L for male participants).	Baseline to Week 24
Secondary	Trough Levels of ABI-H0731 on ABI-H0731 + SOC NUC Therapy		Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
Secondary	Trough Levels of Entecavir (ETV) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy		Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
Secondary	Trough Levels of Tenofovir Alafenamide (TAF) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy		Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
Secondary	Trough Levels of Tenofovir Disoproxil Fumarate (TDF) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy		Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
Secondary	Trough to Peak Ratios of ABI-H0731 on ABI-H0731 + SOC NUC Therapy		Baseline, Weeks 2, 4, 12, and 24
Secondary	Trough to Peak Ratios of SOC NUC on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy		Baseline, Weeks 2, 4, 12, and 24