A Study Evaluating Treatment Intensification With ABI-H0731 in Participants With Chronic Hepatitis B Infection on Nucleos(t)Ide Reverse Transcriptase Inhibitors

Chronic Hepatitis B Clinical Trial

Official title:

A Phase 2a, Multi-Center, Single-Blind, Placebo-Controlled Study Evaluating Treatment Intensification With ABI-H0731 in Subjects With Chronic Hepatitis B Infection on Nucleos(t)Ide Reverse Transcriptase Inhibitors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04454567
• Other study ID #: ABI-H0731-205
• Secondary ID: UTN 1111-1251-71
• Status: Terminated
• Phase: Phase 2
• Start date: November 11, 2020
• Est. completion date: April 8, 2021

Study information

• Verified date: September 2022
• Source: Assembly Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will explore the safety and antiviral activity of ABI-H0731 when added to a nucleos(t)ide reverse transcriptase inhibitor (NrtI) in participants who are partially virologically suppressed.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: April 8, 2021
• Est. primary completion date: April 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Body mass index (BMI) 18 to 36 kg/m^2 and a minimum body weight of 45 kg (inclusive)

• In good general health except for chronic hepatitis B (CHB)

• HBeAg positive or HBeAg negative chronic hepatitis B

• HBV DNA >LLOQ using a commercially available assay with LLOQ=20 IU/mL

• On a stable NrtI regimen (ETV, TDF or TAF) for more than 12 months

• Lack of cirrhosis or advanced liver disease

Exclusion Criteria:

• Current or prior treatment for CHB with lamivudine, telbivudine, adefovir, HBV core inhibitor, or previous treatment with an investigational agent for HBV infection

• Presence of substitutions in the HBV polymerase coding region which may confer reduced susceptibility to NrtIs

• Co-infection with human immunodeficiency virus, hepatitis A virus, hepatitis C virus, hepatitis E virus, or hepatitis D virus

• Females who are lactating or wish to become pregnant during the course of the trial

• History or evidence of advanced liver disease or hepatic decompensation

• Clinically significant cardiac disease including poorly-controlled or unstable hypertension; pulmonary disease; chronic or recurrent renal or urinary tract disease; liver disease other than CHB; endocrine disorder; autoimmune disorder; poorly controlled diabetes mellitus; neuromuscular, musculoskeletal, or mucocutaneous conditions requiring frequent treatment, seizure disorders requiring treatment; ongoing infection 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 subject unsuitable for trial participation

• History of hepatocellular carcinoma (HCC)

• Exclusionary laboratory parameters at Screening:

• Platelet count <100,000/mm^3

• Albumin <lower limit of normal

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

• Direct bilirubin >1.2 × ULN

• ALT >10 × ULN

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

• International Normalized Ratio >1.5 × ULN

• Glomerular filtration rate <50 mL/min/1.73 m^2 by Chronic Kidney Disease Epidemiology Collaboration equation

• Any other laboratory abnormality deemed clinically significant by the Sponsor or the Investigator.

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 tablets orally once daily
• Placebo
Participants will receive placebo to ABI-H0731 tablets orally once daily
• NrtI
Entecavir (ETV), tenofovir alafenamide (TAF), or tenofovir disoproxil fumarate (TDF) SOC according to the respective package insert

Locations

Country	Name	City	State
Hong Kong	Prince of Wales Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
New Zealand	Auckland Clinical Studies	Grafton	Auckland
United States	Institute of Human Virology	Baltimore	Maryland
United States	Infectious Disease Care	Hillsborough	New Jersey
United States	Asia Pacific Liver Center	Los Angeles	California
United States	Northwell Health	Manhasset	New York
United States	Schiff Center for Liver Disease	Miami	Florida
United States	California Liver Research Institute	Pasadena	California
United States	Office of X.M., 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,  Hong Kong,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With an Adverse Event		Baseline and up to 5 months
Primary	Number of Participants With Premature Discontinuation of Treatment		Baseline and up to 5 months
Primary	Number of Participants With a Laboratory Abnormality		Baseline and up to 5 months
Primary	Number of Participants With HBV DNA <Lower Limit of Quantification (LLOQ) at Week 48		Week 48
Secondary	Mean Change From Baseline in log10 HBV DNA		Baseline and up to 5 months
Secondary	Number of Participants With HBV DNA <LLOQ at Each Timepoint		Baseline and up to 5 months
Secondary	Number of Participants With HBV DNA <Limit of Detection (LOD)		Baseline and up to 5 months
Secondary	Mean Change From Baseline in log10 HBV Pregenomic RNA (pgRNA)		Baseline and up to 5 months
Secondary	Number of Participants With HBV pgRNA <LLOQ		Baseline and up to 5 months
Secondary	Mean Change From Baseline in log10 Serum Hepatitis B 'e' Antigen (HBeAg)		Baseline and up to 5 months
Secondary	Mean Change From Baseline in log10 Serum Hepatitis B Core-related Antigen (HBcrAg)		Baseline and up to 5 months
Secondary	Mean Change From Baseline in log10 Serum Hepatitis B Surface Antigen (HBsAg)		Baseline and up to 5 months
Secondary	Number of Participants With Normalized Alanine Aminotransferase (ALT)		Baseline and up to 5 months
Secondary	Plasma Concentrations of ABI-H0731		Baseline and up to 5 months
Secondary	Plasma Concentrations of Entecavir		Baseline and up to 5 months
Secondary	Incidence of HBV Variants Among Participants With Evidence of Non-response to Treatment		Baseline and up to 5 months