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

Chronic Hepatitis B Clinical Trial

Official title:

A Randomized Phase 2a, Multicenter, Open-Label, Multiple-Cohort Study Evaluating Regimens Containing Vebicorvir in Subjects With Chronic Hepatitis B Virus Infection

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04820686
• Other study ID #: ABI-H0731-204
• Status: Terminated
• Phase: Phase 2
• Start date: May 7, 2021
• Est. completion date: March 30, 2023

Study information

• Verified date: October 2023
• Source: Assembly Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

The initial cohort of participants will be enrolled in 3 treatment groups receiving 1) VBR + AB-729 + SOC NrtI, 2) VBR + SOC NrtI, or 3) AB-729 + SOC NrtI for up to 48 weeks. At Week 48, all participants will have an assessment of Treatment Stopping Criteria. Any participant who meets the Treatment Stopping Criteria, will discontinue their assigned treatment including NrtI and will remain in follow-up through Week 96. The participants who do not meet the Treatment Stopping Criteria will continue treatment with NrtI alone and will remain in follow-up through Week 96. Up to an additional 2 cohorts may be added to the study in future protocol amendments.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 65
• Est. completion date: March 30, 2023
• Est. primary completion date: March 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

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.

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• VBR
VBR is an HBV core protein inhibitor. Participants will receive VBR 300 mg tablets orally once daily (QD).
• 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.
• SOC NrtI
Participants will receive their SOC NrtI (ETV, TDF or TAF) tablet orally as per approved package insert.

Locations

Country	Name	City	State
Australia	Saint Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	Footscray Hospital	Footscray	Victoria
Australia	Saint George Hospital - Australia	Kogarah	New South Wales
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Melbourne Health	Parkville	Victoria
Australia	Westmead Hospital	Westmead	New South Wales
Bulgaria	Acibadem City Clinic Tokuda Hospital	Sofia
Bulgaria	Diagnostic Consultative Center Aleksandrovska	Sofia	Sofia City
Bulgaria	University Multiprofile Hospital for Active Treatment St. Ivan Rilski	Sofia
Bulgaria	Nov Rehabilitatsionen Tsentar EOOD	Stara Zagora
Canada	University Hospital - London Health Sciences Centre	London	Ontario
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Centre Hospitalier Université de Québec - Université Laval	Québec
Canada	Toronto Liver Centre	Toronto	Ontario
Canada	Pacific Gastroenterology Associates	Vancouver	British Columbia
Canada	Vancouver Infectious Disease Centre	Vancouver	British Columbia
New Zealand	Auckland Clinical Studies	Auckland
New Zealand	Wellington Regional Hospital	Wellington

Sponsors (2)

Lead Sponsor	Collaborator
Assembly Biosciences	Arbutus Biopharma Corporation

Countries where clinical trial is conducted

Australia,  Bulgaria,  Canada,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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	Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment	Subjects remained on their assigned oral agents (ie, VBR+NrtI for Groups 1 and 2; NrtI for Group 3) until Week 48 laboratory results required for Treatment Stopping Criteria assessment were available so there are some results past Week 48.	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56.
Secondary	Number of Participants With Serum HBsAg Below the Lower Limit of Quantitation (<LLOQ)		Pre-specified time points up to 96 weeks
Secondary	Number of Participants With HBV Deoxyribonucleic Acid (DNA) Not Detected (<5 IU/mL)		Week 48
Secondary	Number of Participants With HBV Ribonucleic Acid (RNA) <LLOQ		Week 48
Secondary	Change From Baseline in Mean log10 HBV RNA On-Treatment	Subjects remained on their assigned oral agents (ie, VBR+NrtI for Groups 1 and 2; NrtI for Group 3) until Week 48 laboratory results required for Treatment Stopping Criteria assessment were available so there are some results past Week 48.	Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 56.
Secondary	Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) On-Treatment		Baseline and Week 48
Secondary	Number of Participants With HBsAg Seroconversion		Week 48
Secondary	Number of Participants With Normal Alanine Aminotransferase (ALT)		Baseline and at pre-specified time points up to 96 weeks
Secondary	Plasma Levels of VBR		Before dosing at Baseline (Day 1) and at pre-specified time points up to 48 weeks, and at Week 52
Secondary	Plasma Levels of AB-729		2 hours after dosing at pre-specified time points up to 40 weeks
Secondary	Plasma Levels of SOC NrtI (ETV, TDF, TAF)		Before dosing at Baseline (Day 1) and at pre-specified time points up to 48 weeks
Secondary	Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment		Weeks 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96.
Secondary	Change From Baseline in Mean log10 HBV RNA Off-Treatment		Weeks 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96.
Secondary	Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment		Weeks 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96.