A Platform Study to Evaluate Investigational Therapies in Chronic Hepatitis B Infection

A Platform Study Evaluating the Efficacy and Safety of Investigational Therapies in Participants With Chronic Hepatitis B Infection (PREVAIL)

This is a Phase 1b/2 platform study framework to evaluate the safety and efficacy of investigational candidate(s) and their combinations as potential treatments for adults with chronic hepatitis B virus infection.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: VIR-2218; Drug: VIR-3434; Drug: PEG-IFNα; Drug: TDF

Detailed Description

VIR-SHB1-V201 (STRIVE) Sub-Protocol A is a Phase 2 study under the PREVAIL platform trial. This is a multi-center, open-label study designed to evaluate the safety and efficacy of regimens containing VIR-3434, VIR-2218, PEGASYS (PEG-IFNα), and nucleotide reverse transcriptase inhibitors (NRTI) in noncirrhotic adult participants with chronic HBV infection that have not received prior NRTI or PEGASYS treatment.

VIR-SHB1-V202 (THRIVE) Sub-Protocol B is a Phase 2 study under the PREVAIL platform trial. This is a multi-center open-label study designed to evaluate the safety and efficacy of regimens containing VIR-3434 and NRTI with or without VIR-2218 in noncirrhotic adult participants with low viral burden of chronic HBV infection.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Study Inquiry; Phone Number: 415-654-5281; Email: clinicaltrials@vir.bio

Study Locations

• France
  • Clichy, France, 92110
    • Investigative Site
  • Nice, France, 06200
    • Investigative Site
  • Rennes, France, 35000
    • Investigative Site
  • Toulouse, France, 31000
    • Investigative Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Investigative Site
  • Sha Tin
    • Hong Kong, Sha Tin, Hong Kong
      • Investigative Site
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Investigative Site
  • Seoul, Korea, Republic of, 5505
    • Investigative Site
  • Yangsan, Korea, Republic of, 50612
    • Investigative Site
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, MD 2025
    • Investigative Site
• Romania
  • Bucharest, Romania, 021105
    • Investigative Site
• United Kingdom
  • Glasgow, United Kingdom, G4 0SF
    • Investigative Site
  • London, United Kingdom, EC1A 7BE
    • Investigative Site
  • London, United Kingdom, SE5 9RS
    • Investigative Site
  • Manchester, United Kingdom, M8 5RB
    • Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female ages 18 or older
• Chronic HBV infection for >/= 6 months
• Chronic HBV infection defined as a positive serum HBsAg, HBV DNA, or HBeAg on 2 occasions at least 6 months apart based on previous or current laboratory documentation
• STRIVE: HBeAg positive or negative, HBV DNA > 2,000 IU/mL, ALT > ULN and ≤ 5x ULN
• THRIVE: Must be/have the following, within the 1-year period prior to screening: HBeAg negative, HBV DNA ≤ 2,000 IU/mL, ALT ≤ ULN

Exclusion Criteria:

• Any clinically significant chronic or acute medical condition that makes the participant unsuitable for participation
• History of clinically significant liver disease from non-HBV etiology
• History or current evidence of hepatic decompensation
• Co-infection with human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis D virus (HDV) or hepatitis E virus (HEV).
• History or clinical evidence of alcohol or drug abuse
• STRIVE and THRIVE: Significant fibrosis or cirrhosis
• STRIVE and THRIVE: History of immune complex disease
• STRIVE and THRIVE: History of autoimmune disorder
• STRIVE and THRIVE: History of allergic reactions, hypersensitivity, or intolerance to monoclonal antibodies, antibody fragments, or any excipients of VIR-3434
• STRIVE: Prior NRTI or PEG-IFN therapy
• STRIVE: History of known contraindication to any interferon product
• THRIVE: Prior NRTI therapy < 24 weeks of study or any prior PEG-IFN therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: STRIVE: Cohort 1a (VIR-3434 + TDF); Participants will receive combination therapy with VIR-3434 + TDF for 44 weeks total	Drug: VIR-3434; VIR-3434 given by subcutaneous injection; Other Names: Tobevibart; Drug: TDF; TDF given orally
Experimental: STRIVE: Cohort 2a (VIR-3434 + TDF); Participants will receive combination therapy with VIR-3434 + TDF for 44 weeks total	Drug: VIR-3434; VIR-3434 given by subcutaneous injection; Other Names: Tobevibart; Drug: TDF; TDF given orally
Experimental: STRIVE: Cohort 3a (VIR-3434 + TDF); Participants will receive combination therapy with VIR-3434 + TDF for 36 or 40 weeks total	Drug: VIR-3434; VIR-3434 given by subcutaneous injection; Other Names: Tobevibart; Drug: TDF; TDF given orally
Experimental: STRIVE: Cohort 4a (VIR-3434 + VIR-2218 + TDF); Participants will receive combination therapy with VIR-3434 + VIR-2218 + TDF for 20 or 44 weeks total	Drug: VIR-2218; VIR-2218 given by subcutaneous injection; Other Names: Elebsiran; Drug: VIR-3434; VIR-3434 given by subcutaneous injection; Other Names: Tobevibart; Drug: TDF; TDF given orally
Experimental: STRIVE: Cohort 5a (VIR-3434 + VIR-2218 + TDF + PEG-IFNα); Participants will receive combination therapy with VIR-3434 + VIR-2218 +TDF + PEG-IFNα for 48 weeks total	Drug: VIR-2218; VIR-2218 given by subcutaneous injection; Other Names: Elebsiran; Drug: VIR-3434; VIR-3434 given by subcutaneous injection; Other Names: Tobevibart; Drug: PEG-IFNα; PEG-IFNα given by subcutaneous injection; Drug: TDF; TDF given orally
Experimental: THRIVE: Cohort 1b (VIR-3434 + TDF); Participants will receive combination therapy with VIR-3434 + TDF for 44 weeks	Drug: VIR-3434; VIR-3434 given by subcutaneous injection; Other Names: Tobevibart; Drug: TDF; TDF given orally
Experimental: THRIVE: Cohort 2b (VIR-3434 + VIR-2218 + TDF); Participants will receive combination therapy with VIR-3434 + VIR-2218 + TDF for 44 weeks total	Drug: VIR-2218; VIR-2218 given by subcutaneous injection; Other Names: Elebsiran; Drug: VIR-3434; VIR-3434 given by subcutaneous injection; Other Names: Tobevibart; Drug: TDF; TDF given orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
STRIVE and THRIVE: Proportion of participants achieving suppression of HBV DNA (< LLOQ) with HBsAg loss (< 0.05 IU/mL) at the end of treatment	Up to 72 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
STRIVE and THRIVE: Proportion of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)	Up to 96 weeks
STRIVE and THRIVE: Proportion of participants with serum HBsAg ≤ 10 IU/mL at end of treatment	Up to 48 weeks
STRIVE and THRIVE: Proportion of participants with serum HBsAg ≤ 10 IU/mL at 24 weeks post-end of treatment	Up to 72 weeks
STRIVE and THRIVE: Serum HBsAg levels and change from baseline across timepoints in the study	Up to 96 weeks
STRIVE and THRIVE: Serum HBsAg level at nadir during the study	Up to 96 weeks
STRIVE and THRIVE: Time to achieve nadir of serum HBsAg during the study	Up to 96 weeks
STRIVE and THRIVE: Time to achieve serum HBsAg loss (< 0.05 IU/mL)	Up to 96 weeks
STRIVE and THRIVE: Proportion of participants with HBsAg loss with anti-HBs seroconversion at end of treatment and at 24 weeks post-end of treatment	Up to 76 weeks
STRIVE: Proportion of participants achieving sustained suppression of HBV DNA (< LLOQ) with HBsAg loss (< 0.05 IU/mL) after discontinuation of all treatment at 24 weeks and at the F48 Follow-Up visit	Up to 96 weeks
STRIVE: Proportion of participants with HBsAg loss (<0.05 IU/mL) at end of treatment and at 24 weeks post-end of treatment	Up to 72 weeks
STRIVE: Proportion of participants achieving sustained suppression of HBV DNA (< LLOQ) after discontinuation of all treatment at 24 weeks and at the F48 Follow-Up visit	Up to 96 weeks
STRIVE: For HBeAg-positive participants: proportion of participants with HBeAg loss (undetectable HBeAg) and/or anti-HBe seroconversion	Up to 72 weeks
STRIVE: Incidence and titers of anti-drug antibodies (ADA; if applicable) to VIR-3434	Up to 96 weeks
STRIVE: Mean change in serum HBsAg level from baseline across timepoints in the study	Up to 96 weeks
STRIVE: Proportion of participants achieving HBV DNA (< LLOQ) across timepoints in the study	Up to 96 weeks
STRIVE: Proportion of participants achieving ALT ≤ ULN across timepoints in the study	Up to 96 weeks
THRIVE: Proportion of participants achieving sustained suppression of HBV DNA (< LLOQ) with HBsAg loss (< 0.05 IU/mL) after discontinuation of all treatment at 24 weeks and at 48 weeks	Up to 92 weeks
THRIVE: Proportion of participants achieving HBsAg loss (< 0.05 IU/mL) at end of treatment and at 24 weeks post-end of treatment	Up to 44 weeks
THRIVE: Proportion of participants achieving sustained suppression of HBV DNA (< LLOQ) after discontinuation of all treatment at 24 weeks and at 48 weeks	Up to 68 weeks
THRIVE: Incidence and titers of ADA (if applicable) to VIR-3434	Up to 92 weeks
THRIVE: Mean change in serum HBsAg level from baseline across timepoints in the study	Up to 92 weeks
THRIVE: Proportion of participants achieving HBV DNA (< LLOQ)	Up to 92 weeks

Collaborators and Investigators

• Sponsor: Vir Biotechnology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2023
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: November 3, 2022
• First Submitted That Met QC Criteria: November 3, 2022
• First Posted (Actual): November 10, 2022

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Hepatitis; HBV; Chronic Hepatitis B; Hepatitis B Virus
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: VIR-MHB1-V200

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes