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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04454567




Registration number
NCT04454567
Ethics application status
Date submitted
18/06/2020
Date registered
1/07/2020

Titles & IDs
Public title
A Study Evaluating Treatment Intensification With ABI-H0731 in Participants With Chronic Hepatitis B Infection on Nucleos(t)Ide Reverse Transcriptase Inhibitors
Scientific 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
Secondary ID [1] 0 0
UTN 1111-1251-7136
Secondary ID [2] 0 0
ABI-H0731-205
Universal Trial Number (UTN)
UTN 1111-1251-7136
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ABI-H0731
Treatment: Drugs - Placebo
Treatment: Drugs - NrtI

Experimental: ABI-H0731 + SOC NrtI - Participants with chronic hepatitis B virus (HBV) infection with partial virologic suppression on NrtI alone will receive ABI-H0731 300 mg once daily plus standard of care (SOC) NrtI for 96 weeks, followed by SOC NrtI alone for an additional 24 weeks (120 weeks total).

Placebo comparator: Placebo + SOC NrtI - Participants with chronic HBV infection with partial virologic suppression on NrtI alone will receive placebo to ABI-H0731 once daily plus SOC NrtI for 48 weeks, followed by ABI-H0731 300 mg once daily plus SOC NrtI for Weeks 48 to 96, followed by SOC NrtI alone for Weeks 96 to 120.


Treatment: Drugs: ABI-H0731
Participants will receive ABI-H0731 tablets orally once daily

Treatment: Drugs: Placebo
Participants will receive placebo to ABI-H0731 tablets orally once daily

Treatment: Drugs: NrtI
Entecavir (ETV), tenofovir alafenamide (TAF), or tenofovir disoproxil fumarate (TDF) SOC according to the respective package insert
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With an Adverse Event
Timepoint [1] 0 0
Baseline and up to 5 months
Primary outcome [2] 0 0
Number of Participants With Premature Discontinuation of Treatment
Timepoint [2] 0 0
Baseline and up to 5 months
Primary outcome [3] 0 0
Number of Participants With a Laboratory Abnormality
Timepoint [3] 0 0
Baseline and up to 5 months
Primary outcome [4] 0 0
Number of Participants With HBV DNA <Lower Limit of Quantification (LLOQ) at Week 48
Timepoint [4] 0 0
Week 48
Secondary outcome [1] 0 0
Mean Change From Baseline in log10 HBV DNA
Timepoint [1] 0 0
Baseline and up to 5 months
Secondary outcome [2] 0 0
Number of Participants With HBV DNA <LLOQ at Each Timepoint
Timepoint [2] 0 0
Baseline and up to 5 months
Secondary outcome [3] 0 0
Number of Participants With HBV DNA <Limit of Detection (LOD)
Timepoint [3] 0 0
Baseline and up to 5 months
Secondary outcome [4] 0 0
Mean Change From Baseline in log10 HBV Pregenomic RNA (pgRNA)
Timepoint [4] 0 0
Baseline and up to 5 months
Secondary outcome [5] 0 0
Number of Participants With HBV pgRNA <LLOQ
Timepoint [5] 0 0
Baseline and up to 5 months
Secondary outcome [6] 0 0
Mean Change From Baseline in log10 Serum Hepatitis B 'e' Antigen (HBeAg)
Timepoint [6] 0 0
Baseline and up to 5 months
Secondary outcome [7] 0 0
Mean Change From Baseline in log10 Serum Hepatitis B Core-related Antigen (HBcrAg)
Timepoint [7] 0 0
Baseline and up to 5 months
Secondary outcome [8] 0 0
Mean Change From Baseline in log10 Serum Hepatitis B Surface Antigen (HBsAg)
Timepoint [8] 0 0
Baseline and up to 5 months
Secondary outcome [9] 0 0
Number of Participants With Normalized Alanine Aminotransferase (ALT)
Timepoint [9] 0 0
Baseline and up to 5 months
Secondary outcome [10] 0 0
Plasma Concentrations of ABI-H0731
Timepoint [10] 0 0
Baseline and up to 5 months
Secondary outcome [11] 0 0
Plasma Concentrations of Entecavir
Timepoint [11] 0 0
Baseline and up to 5 months
Secondary outcome [12] 0 0
Incidence of HBV Variants Among Participants With Evidence of Non-response to Treatment
Timepoint [12] 0 0
Baseline and up to 5 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/11/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/04/2021
Sample size
Target
Accrual to date
Final
2
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
New Jersey
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
Hong Kong
State/province [7] 0 0
Hong Kong
Country [8] 0 0
New Zealand
State/province [8] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Assembly Biosciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Steven Knox
Address 0 0
Assembly Biosciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04454567