A Study Evaluating ABI-H0731+ Entecavir vs Entecavir Alone for the Treatment of Viremic HBeAg-positive Participants With Chronic Hepatitis B Virus Infection (cHBV)

Chronic Hepatitis B Clinical Trial

Official title:

A Phase 2a, Multi-center, Double-blind, Placebo-controlled Study Evaluating ABI-H0731+ Entecavir vs Entecavir Alone for the Treatment of Viremic HBeAg-positive Patients With Chronic Hepatitis B

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03577171
• Other study ID #: ABI-H0731-202
• Status: Completed
• Phase: Phase 2
• Start date: June 19, 2018
• Est. completion date: June 21, 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) entecavir (ETV) is safe and effective in participants with chronic hepatitis B infection (cHBV)

Description:

This is a Phase 2a, multi-center, double-blind, placebo-controlled study evaluating ABI-H0731+ ETV vs ETV alone for the treatment of viremic hepatitis B "e" antigen (HBeAg)-positive participants with cHBV.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: June 21, 2019
• Est. primary completion date: June 21, 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

• HBeAg-positive at screening

• In good general health except for cHBV

• HBV viral load =2×105 IU/mL

• Hepatitis B surface antigen (HBsAg) >1000 IU/mL at screening

Key Exclusion Criteria:

• Any prior treatment with lamivudine or telbivudine, previous treatment with an investigational agent for HBV other than ABI-H0731; or any other SOC treatment for >4 weeks

• 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:

• Platelet count <100,000/mm3

• Albumin <lower limit of normal (LLN)

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

• Alanine aminotransferase (ALT) >10×ULN at screening

• Serum alpha fetoprotein (AFP) =100 ng/mL. If AFP at Screening is >ULN but <100 ng/mL, participant is eligible if a hepatic imaging study prior to the initiation of study drug reveals no lesions suspicious of possible HCC

• 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 300mg QD of ABI-H0731 tablets orally.
• SOC ETV
Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.
• Placebo Oral Tablet
Participants will receive matching QD placebo tablets orally.

Locations

Country	Name	City	State
Canada	Toronto Liver Center	Toronto	Ontario
Canada	GI Research Institute	Vancouver	British Columbia
Hong Kong	University of Hong Kong, Queen Mary Hospital	Hong Kong
New Zealand	Waikato Hospital	Hamilton
United Kingdom	King's College London	London
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Southern California Research Center	Coronado	California
United States	Asia Pacific Liver Center	Los Angeles	California
United States	NYU Langone Health	New York	New York
United States	Xiaoli Ma MD	Philadelphia	Pennsylvania
United States	Research and Education	San Diego	California
United States	Quest Clinical Research	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Assembly Biosciences

Countries where clinical trial is conducted

United States,  Canada,  Hong Kong,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Mean log10 HBV DNA From Baseline (Day 1) to Week 12 or Week 24 on ABI H0731 + SOC ETV as Compared to Placebo + SOC ETV	Hepatitis B virus (HBV) DNA was measured using COBAS TaqMan Version 2.0. The lower limit of quantitation (LLOQ) was 20 IU/mL and the limit of detection (LOD) was 10 IU/mL.	Baseline, Week 12, and Week 24
Secondary	Number of Participants 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 + SOC ETV as Compared to Placebo + SOC ETV		Baseline to Week 24
Secondary	Number of Participants With a Decline in Viral DNA to Below Limit of Quantitation on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV	HBV DNA was measured using COBAS TaqMan Version 2.0. The LLOQ was 20 IU/mL and the LOD was 10 IU/mL. The number of participants with HBV DNA below the limit of quantitation (<20 IU/mL) and target detected (=10 IU/mL) was assessed.	Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24
Secondary	Median Time to Viral Suppression, Defined as HBV DNA <20 IU/mL, on ABI-H0731 + ETV as Compared to Placebo + ETV	Median time to viral suppression will be calculated and evaluated between participants on ABI-H0731 + ETV as compared to placebo + ETV.	Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24
Secondary	Number of Participants With Emergence of Resistant HBV Variants on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV	Emergence of a resistant HBV variant was defined as an increase of =1 log10 IU/mL from the nadir in HBV DNA.	Up to Week 36
Secondary	Trough Levels of ABI-H0731 on ABI-H0731 + SOC ETV Therapy		Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
Secondary	Trough Levels of ETV on ABI-H0731 + ETV Therapy as Compared With Placebo + ETV Therapy		Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
Secondary	Trough to Peak Ratios of ABI-H0731 on ABI-H0731 + ETV Therapy		Baseline, Weeks 2, 4, 12, and 24
Secondary	Trough to Peak Ratios of ETV on ABI-H0731 + ETV Therapy as Compared With Placebo + ETV Therapy		Baseline, Weeks 2, 4, 12, 24, and 28