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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04820686




Registration number
NCT04820686
Ethics application status
Date submitted
25/03/2021
Date registered
29/03/2021

Titles & IDs
Public title
A Study Evaluating Treatment Regimens Containing Vebicorvir (ABI-H0731) in Participants With Chronic Hepatitis B Infection
Scientific title
A Randomized Phase 2a, Multicenter, Open-Label, Multiple-Cohort Study Evaluating Regimens Containing Vebicorvir in Subjects With Chronic Hepatitis B Virus Infection
Secondary ID [1] 0 0
ABI-H0731-204
Universal Trial Number (UTN)
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 - VBR
Treatment: Drugs - AB-729
Treatment: Drugs - SOC NrtI

Experimental: VBR + AB-729 + SOC NrtI - Participants with cHBV received VBR + AB-729 + SOC NrtI for 48 weeks followed by 48 weeks in follow-up.

Other: VBR + SOC NrtI - Participants with cHBV received VBR + SOC NrtI for 48 weeks followed by 48 weeks in follow-up. This treatment was used as a reference regimen.

Other: AB-729 + SOC NrtI - Participants with cHBV received AB-729 + SOC NrtI for 48 weeks followed by 48 weeks in follow-up. This treatment was used as a reference regimen.


Treatment: Drugs: VBR
VBR is an HBV core protein inhibitor. Participants will receive VBR 300 mg tablets orally once daily (QD).

Treatment: Drugs: AB-729
AB-729 is a small interfering ribonucleic acid (siRNA) inhibitor of HBV. Participants will receive a 60-mg subcutaneous injection of AB-729 once every 8 weeks.

Treatment: Drugs: SOC NrtI
Participants will receive their SOC NrtI (ETV, TDF or TAF) tablet orally as per approved package insert.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With One or More Adverse Events (AEs)
Timepoint [1] 0 0
AEs were collected from the time of signing the informed consent until the final follow-up visit, up to 96 weeks.
Primary outcome [2] 0 0
Number of Participants With Premature Treatment Discontinuation Due to AEs
Timepoint [2] 0 0
AEs were collected from the time of signing the informed consent until the final follow-up visit, up to 96 weeks.
Primary outcome [3] 0 0
Number of Participants With One or More Abnormal Laboratory Result
Timepoint [3] 0 0
Laboratory results were collected from the time of signing the informed consent until the study was early terminated, up to 96 weeks.
Secondary outcome [1] 0 0
Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment
Timepoint [1] 0 0
Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56.
Secondary outcome [2] 0 0
Number of Participants With Serum HBsAg Below the Lower Limit of Quantitation (<LLOQ)
Timepoint [2] 0 0
Pre-specified time points up to 96 weeks
Secondary outcome [3] 0 0
Number of Participants With HBV Deoxyribonucleic Acid (DNA) Not Detected (<5 IU/mL)
Timepoint [3] 0 0
Week 48
Secondary outcome [4] 0 0
Number of Participants With HBV Ribonucleic Acid (RNA) <LLOQ
Timepoint [4] 0 0
Week 48
Secondary outcome [5] 0 0
Change From Baseline in Mean log10 HBV RNA On-Treatment
Timepoint [5] 0 0
Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 56.
Secondary outcome [6] 0 0
Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) On-Treatment
Timepoint [6] 0 0
Baseline and Week 48
Secondary outcome [7] 0 0
Number of Participants With HBsAg Seroconversion
Timepoint [7] 0 0
Week 48
Secondary outcome [8] 0 0
Number of Participants With Normal Alanine Aminotransferase (ALT)
Timepoint [8] 0 0
Baseline and at pre-specified time points up to 96 weeks
Secondary outcome [9] 0 0
Plasma Levels of VBR
Timepoint [9] 0 0
Before dosing at Baseline (Day 1) and at pre-specified time points up to 48 weeks, and at Week 52
Secondary outcome [10] 0 0
Plasma Levels of AB-729
Timepoint [10] 0 0
2 hours after dosing at pre-specified time points up to 40 weeks
Secondary outcome [11] 0 0
Plasma Levels of SOC NrtI (ETV, TDF, TAF)
Timepoint [11] 0 0
Before dosing at Baseline (Day 1) and at pre-specified time points up to 48 weeks
Secondary outcome [12] 0 0
Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment
Timepoint [12] 0 0
Weeks 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96.
Secondary outcome [13] 0 0
Change From Baseline in Mean log10 HBV RNA Off-Treatment
Timepoint [13] 0 0
Weeks 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96.
Secondary outcome [14] 0 0
Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment
Timepoint [14] 0 0
Weeks 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96.

Eligibility
Key inclusion criteria
* Body mass index (BMI) 18 to 36 kg/m^2 and a minimum body weight of 45 kg (inclusive)
* Female participants must be non-pregnant and have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day 1
* Chronic Hepatitis B defined as HBV infection documented for =6 months prior to Screening
* Hepatitis B 'e' antigen (HBeAg) negative at least 3 months prior to Screening Visit (historical documentation) AND at the Screening Visit
* Virologically suppressed on SOC NrtI therapy with nonquantifiable HBV DNA for at least 6 months prior to Screening
* On a stable SOC NrtI regimen of ETV, TDF, or TAF for >12 months
* HBsAg =100 international units/mL at Screening
* Lack of bridging fibrosis or cirrhosis
* Agreement to comply with protocol-specified contraceptive requirements
* In good general health, except for cHBV, in the opinion of the Investigator
* Able to take oral medication and willing to receive subcutaneous injections of AB-729.
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis D virus (HDV), acute hepatitis A virus (HAV), or acute hepatitis E virus (HEV)
* Females who are lactating or wish to become pregnant during the course of the study
* History of liver transplant or evidence of advanced liver disease, cirrhosis, or hepatic decompensation at any time prior to, or at the time of Screening
* History of persistent alcohol abuse or illicit drug abuse within 3 years prior to Screening
* Clinically significant diseases or conditions, such as cardiac disease, including poorly-controlled or unstable hypertension; pulmonary disease; chronic or recurrent renal or urinary tract disease; liver disease other than cHBV; 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 study participation
* History of hepatocellular carcinoma (HCC)
* History of malignancy other than HCC unless the subject's malignancy has been in complete remission off chemotherapy and without additional medical or surgical interventions during the 3 years before Screening
* History or presence at Screening of electrocardiogram (ECG) abnormalities deemed clinically significant, in the opinion of the Investigator
* History of hypersensitivity or idiosyncratic reaction to any components or excipients of the investigational drugs
* History of any significant food or drug-related allergic reactions such as anaphylaxis or Stevens-Johnson syndrome
* Exclusionary laboratory results at Screening:

1. Platelet count <100,000/mm^3
2. Albumin <3 g/dL
3. Direct bilirubin >1.2× upper limit of normal (ULN)
4. ALT =5× ULN
5. Serum alpha fetoprotein (AFP) =100 ng/mL. If AFP at Screening is > ULN but <100 ng/mL, the subject is eligible if hepatic imaging prior to initiation of study drug reveals no lesions indicative of possible HCC
6. International Normalized Ratio (INR) >1.5× ULN
7. Estimated creatinine clearance (CrCl) <50 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight at Screening
8. Any other laboratory abnormality deemed clinically significant by the Investigator
* Current or prior use of prohibited (per protocol) concomitant medications from 28 days prior to Day 1.
* Current or prior treatment for cHBV with:

* Lamivudine, telbivudine or adefovir (any duration)
* HBV core inhibitor (any duration)
* siRNA or other oligonucleotide therapeutic (any duration)
* Interferon in the 6 months prior to Screening
* Any investigational agent for cHBV in the 6 months prior to Screening.
* Participation in another clinical study of a drug or device whereby the last investigational drug/device administration is within 60 days or 5 half-lives prior to study start.

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
Open (masking not used)
Who is / are masked / blinded?



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
7/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/03/2023
Sample size
Target
Accrual to date
Final
65
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Saint Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
Saint George Hospital - Australia - Kogarah
Recruitment hospital [3] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [4] 0 0
Westmead Hospital - Westmead
Recruitment hospital [5] 0 0
Footscray Hospital - Footscray
Recruitment hospital [6] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [7] 0 0
Melbourne Health - Parkville
Recruitment hospital [8] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2170 - Liverpool
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment postcode(s) [5] 0 0
3011 - Footscray
Recruitment postcode(s) [6] 0 0
3004 - Melbourne
Recruitment postcode(s) [7] 0 0
3050 - Parkville
Recruitment postcode(s) [8] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Bulgaria
State/province [1] 0 0
Sofia City
Country [2] 0 0
Bulgaria
State/province [2] 0 0
Sofia
Country [3] 0 0
Bulgaria
State/province [3] 0 0
Stara Zagora
Country [4] 0 0
Canada
State/province [4] 0 0
British Columbia
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
Canada
State/province [6] 0 0
Québec
Country [7] 0 0
New Zealand
State/province [7] 0 0
Auckland
Country [8] 0 0
New Zealand
State/province [8] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Assembly Biosciences
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Arbutus Biopharma Corporation
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Address 0 0
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)?
No
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 not provided in https://clinicaltrials.gov/study/NCT04820686