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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04820686
Recruitment Status : Active, not recruiting
First Posted : March 29, 2021
Last Update Posted : March 31, 2022
Sponsor:
Collaborator:
Arbutus Biopharma Corporation
Information provided by (Responsible Party):
Assembly Biosciences

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).

Condition or disease Intervention/treatment Phase
Chronic Hepatitis B Drug: VBR Drug: AB-729 Drug: SOC NrtI Phase 2

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase 2a, Multicenter, Open-Label, Multiple-Cohort Study Evaluating Regimens Containing Vebicorvir in Subjects With Chronic Hepatitis B Virus Infection
Actual Study Start Date : May 7, 2021
Estimated Primary Completion Date : January 10, 2024
Estimated Study Completion Date : January 10, 2024


Arm Intervention/treatment
Experimental: VBR + AB-729 + SOC NrtI
Participants with cHBV will receive VBR + AB-729 + SOC NrtI for 48 weeks followed by 48 weeks in follow-up.
Drug: VBR
VBR is an HBV core protein inhibitor. Participants will receive VBR 300 mg tablets orally once daily (QD).
Other Name: Vebicorvir, ABI-H0731

Drug: 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.

Drug: SOC NrtI
Participants will receive their SOC NrtI (ETV, TDF or TAF) tablet orally as per approved package insert.
Other Names:
  • Entecavir (ETV)
  • Tenofovir disoproxil fumarate (TDF)
  • Tenofovir alafenamide (TAF)

VBR + SOC NrtI
Participants with cHBV will receive VBR + SOC NrtI for 48 weeks followed by 48 weeks in follow-up. This treatment will be used as a reference regimen.
Drug: VBR
VBR is an HBV core protein inhibitor. Participants will receive VBR 300 mg tablets orally once daily (QD).
Other Name: Vebicorvir, ABI-H0731

Drug: SOC NrtI
Participants will receive their SOC NrtI (ETV, TDF or TAF) tablet orally as per approved package insert.
Other Names:
  • Entecavir (ETV)
  • Tenofovir disoproxil fumarate (TDF)
  • Tenofovir alafenamide (TAF)

AB-729 + SOC NrtI
Participants with cHBV will receive AB-729 + SOC NrtI for 48 weeks followed by 48 weeks in follow-up. This treatment will be used as a reference regimen.
Drug: 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.

Drug: SOC NrtI
Participants will receive their SOC NrtI (ETV, TDF or TAF) tablet orally as per approved package insert.
Other Names:
  • Entecavir (ETV)
  • Tenofovir disoproxil fumarate (TDF)
  • Tenofovir alafenamide (TAF)




Primary Outcome Measures :
  1. Number of Participants with One or More Adverse Events [ Time Frame: Up to 96 weeks ]
  2. Number of Participants with Premature Study Discontinuation [ Time Frame: Up to 96 weeks ]
  3. Number of Participants With One or More Abnormal Laboratory Result [ Time Frame: Up to 96 weeks ]

Secondary Outcome Measures :
  1. Change from Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) [ Time Frame: Baseline and at pre-specified time points up to 96 weeks ]
  2. Number of Participants with Serum HBsAg Below the Lower Limit of Quantitation (<LLOQ) [ Time Frame: Pre-specified time points up to 96 weeks ]
  3. Number of Participants with HBV Deoxyribonucleic Acid (DNA) not Detected (<5 International Units/mL) [ Time Frame: Week 48 ]
  4. Number of Participants with HBV Ribonucleic Acid (RNA) <LLOQ [ Time Frame: Week 48 ]
  5. Change from Baseline in Mean log10 HBV RNA [ Time Frame: Baseline and at pre-specified time points up to 96 weeks ]
  6. Change from Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) [ Time Frame: Baseline and at pre-specified time points up to 96 weeks ]
  7. Number of Participants with HBsAg Seroconversion [ Time Frame: Week 48 ]
  8. Number of Participants with Normal Alanine Aminotransferase (ALT) [ Time Frame: Baseline and at pre-specified time points up to 96 weeks ]
  9. Plasma Levels of VBR [ Time Frame: Before dosing at Baseline (Day 1) and at pre-specified time points up to 48 weeks, and at Week 52 ]
  10. Plasma Levels of AB-729 [ Time Frame: 2 hours after dosing at pre-specified time points up to 40 weeks ]
  11. Plasma Levels of SOC NrtI (ETV, TDF, TAF) [ Time Frame: Before dosing at Baseline (Day 1) and at pre-specified time points up to 48 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04820686


Locations
Show Show 20 study locations
Sponsors and Collaborators
Assembly Biosciences
Arbutus Biopharma Corporation
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Assembly Biosciences
ClinicalTrials.gov Identifier: NCT04820686    
Other Study ID Numbers: ABI-H0731-204
First Posted: March 29, 2021    Key Record Dates
Last Update Posted: March 31, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assembly Biosciences:
cHBV
HBV
hepatitis B
vebicorvir
VBR
AB-729
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Hepatitis, Chronic
Infections
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Blood-Borne Infections
Communicable Diseases
Hepadnaviridae Infections
DNA Virus Infections
Tenofovir
Entecavir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents