A Study Evaluating Treatment Regimens Containing Vebicorvir (ABI-H0731) in Participants With Chronic Hepatitis B Infection

NCT04820686 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: ABI-H0731-204
• Study Type: interventional
• Target: 65
• Locations: 4 countries
• Sites: 20

Brief Summary

The purpose of this study is to determine if vebicorvir (VBR, ABI-H0731) in combination with AB-729 is safe and effective in participants with chronic hepatitis B infection (cHBV) receiving a standard of care nucleos(t)ide/reverse transcriptase inhibitor (SOC NrtI).

Conditions

Chronic Hepatitis B

Keywords

cHBV; HBV; hepatitis B; vebicorvir; VBR; AB-729

Outcome Measures

Primary Outcomes (3)

• Number of Participants With One or More Adverse Events (AEs)

  AEs were collected from the time of signing the informed consent until the final follow-up visit, up to 96 weeks.

• Number of Participants With Premature Treatment Discontinuation Due to AEs

  AEs were collected from the time of signing the informed consent until the final follow-up visit, up to 96 weeks.

• Number of Participants With One or More Abnormal Laboratory Result

  Laboratory results were collected from the time of signing the informed consent until the study was early terminated, up to 96 weeks.

Secondary Outcomes (14)

• Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment

  Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56.

• Number of Participants With Serum HBsAg Below the Lower Limit of Quantitation (<LLOQ)

  Pre-specified time points up to 96 weeks

• Number of Participants With HBV Deoxyribonucleic Acid (DNA) Not Detected (<5 IU/mL)

  Week 48

• Number of Participants With HBV Ribonucleic Acid (RNA) <LLOQ

  Week 48

• Change From Baseline in Mean log10 HBV RNA On-Treatment

  Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 56.

Study Arms (3)

VBR + AB-729 + SOC NrtI

EXPERIMENTAL

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

Drug: VBR; Drug: AB-729; Drug: SOC NrtI

VBR + SOC NrtI

OTHER

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.

Drug: VBR; Drug: SOC NrtI

AB-729 + SOC NrtI

OTHER

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.

Drug: AB-729; Drug: SOC NrtI

Interventions

VBR DRUG

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

Also known as: Vebicorvir, ABI-H0731

VBR + AB-729 + SOC NrtI; VBR + SOC NrtI

AB-729 DRUG

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.

AB-729 + SOC NrtI; VBR + AB-729 + SOC NrtI

SOC NrtI DRUG

Participants will receive their SOC NrtI (ETV, TDF or TAF) tablet orally as per approved package insert.

Also known as: Entecavir (ETV), Tenofovir disoproxil fumarate (TDF), Tenofovir alafenamide (TAF)

AB-729 + SOC NrtI; VBR + AB-729 + SOC NrtI; VBR + SOC NrtI

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Platelet count \<100,000/mm\^3
• Albumin \<3 g/dL
• Direct bilirubin \>1.2× upper limit of normal (ULN)
• ALT ≥5× ULN
• 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

Sponsors & Collaborators

• Assembly Biosciences: lead
• Arbutus Biopharma Corporation: collaborator

Study Sites (20)

Saint Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Saint George Hospital - Australia

Kogarah, New South Wales, 2217, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Footscray Hospital

Footscray, Victoria, 3011, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Melbourne Health

Parkville, Victoria, 3050, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Diagnostic Consultative Center Aleksandrovska

Sofia, Sofia-Grad, 1431, Bulgaria

Location

Acibadem City Clinic Tokuda Hospital

Sofia, 1407, Bulgaria

Location

University Multiprofile Hospital for Active Treatment St. Ivan Rilski

Sofia, 1431, Bulgaria

Location

Nov Rehabilitatsionen Tsentar EOOD

Stara Zagora, 6000, Bulgaria

Location

Vancouver Infectious Disease Centre

Vancouver, British Columbia, V6Z 2C7, Canada

Location

Pacific Gastroenterology Associates

Vancouver, British Columbia, V6Z 2K5, Canada

Location

University Hospital - London Health Sciences Centre

London, Ontario, N6A 2C2, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

Toronto Liver Centre

Toronto, Ontario, M6H 3M1, Canada

Location

Centre Hospitalier Université de Québec - Université Laval

Québec, G1V 4G2, Canada

Location

Auckland Clinical Studies

Auckland, 1010, New Zealand

Location

Wellington Regional Hospital

Wellington, 6021, New Zealand

Location

Related Publications (1)

• Ligat G, Verrier ER, Nassal M, Baumert TF. Hepatitis B virus-host interactions and novel targets for viral cure. Curr Opin Virol. 2021 Aug;49:41-51. doi: 10.1016/j.coviro.2021.04.009. Epub 2021 May 22.

  PMID: 34029994 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis B

Interventions

entecavir; Tenofovir; tenofovir alafenamide

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Study ABI-H0731-204 was terminated early by the study Sponsor for strategic reasons to prioritize research and development efforts on finite and curative HBV therapies. As a result, not all subjects completed Week 96 and some outcome measures were impacted.

Results Point of Contact

• Title: Director of Clinical Operations
• Organization: Assembly BioSciences Inc.

psalstrand@assemblybio.com

415-366-5172

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2021
• First Posted: March 29, 2021
• Study Start: May 7, 2021
• Primary Completion: March 30, 2023
• Study Completion: March 30, 2023
• Last Updated: November 14, 2023
• Results First Posted: November 14, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (2); CA (6); BU (4); AU (8)