Clinical trial NCT04454567: A Study Evaluating Treatment Intensification With ABI-H0731 in Participants With Chronic Hepatitis B Infection on Nucleos(t)Ide Reverse Transcriptase Inhibitors
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Lead sponsor: Assembly Biosciences
Sponsor class: INDUSTRY
First posted: 2020-07-01
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With an Adverse Event
timeFrame: Baseline and up to 5 months
measure: Number of Participants With Premature Discontinuation of Treatment
timeFrame: Baseline and up to 5 months
measure: Number of Participants With a Laboratory Abnormality
timeFrame: Baseline and up to 5 months
measure: Number of Participants With HBV DNA <Lower Limit of Quantification (LLOQ) at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Mean Change From Baseline in log10 HBV DNA
timeFrame: Baseline and up to 5 months
measure: Number of Participants With HBV DNA <LLOQ at Each Timepoint
timeFrame: Baseline and up to 5 months
measure: Number of Participants With HBV DNA <Limit of Detection (LOD)
timeFrame: Baseline and up to 5 months
measure: Mean Change From Baseline in log10 HBV Pregenomic RNA (pgRNA)
timeFrame: Baseline and up to 5 months
measure: Number of Participants With HBV pgRNA <LLOQ
timeFrame: Baseline and up to 5 months
measure: Mean Change From Baseline in log10 Serum Hepatitis B 'e' Antigen (HBeAg)
timeFrame: Baseline and up to 5 months
measure: Mean Change From Baseline in log10 Serum Hepatitis B Core-related Antigen (HBcrAg)
timeFrame: Baseline and up to 5 months
measure: Mean Change From Baseline in log10 Serum Hepatitis B Surface Antigen (HBsAg)
timeFrame: Baseline and up to 5 months
measure: Number of Participants With Normalized Alanine Aminotransferase (ALT)
timeFrame: Baseline and up to 5 months
measure: Plasma Concentrations of ABI-H0731
timeFrame: Baseline and up to 5 months
measure: Plasma Concentrations of Entecavir
timeFrame: Baseline and up to 5 months
measure: Incidence of HBV Variants Among Participants With Evidence of Non-response to Treatment
timeFrame: Baseline and up to 5 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Asia Pacific Liver Center
state: California
city: Pasadena
country: United States
facility: California Liver Research Institute
state: California
city: San Diego
country: United States
facility: Research and Education
state: California
city: San Francisco
country: United States
facility: Quest Clinical Research
state: California
city: Miami
country: United States
facility: Schiff Center for Liver Disease
state: Florida
city: Baltimore
country: United States
facility: Institute of Human Virology
state: Maryland
city: Hillsborough
country: United States
facility: Infectious Disease Care
state: New Jersey
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: Philadelphia
country: United States
facility: Office of X.M., MD
state: Pennsylvania
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Grafton
country: New Zealand
facility: Auckland Clinical Studies
state: Auckland
Study officials:
affiliation: Assembly Biosciences
name: Steven Knox
role: STUDY_DIRECTOR
References: