A Platform Study to Evaluate Investigational Therapies in Chronic Hepatitis B Infection
Phase 1
Active, not recruiting
- Conditions
- Hepatitis B, Chronic
- Interventions
- Registration Number
- NCT05612581
- Lead Sponsor
- Vir Biotechnology, Inc.
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 150
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description STRIVE: Cohort 1a (VIR-3434 + TDF) VIR-3434 Participants will receive combination therapy with VIR-3434 + TDF for 44 weeks total STRIVE: Cohort 1a (VIR-3434 + TDF) TDF Participants will receive combination therapy with VIR-3434 + TDF for 44 weeks total STRIVE: Cohort 2a (VIR-3434 + TDF) VIR-3434 Participants will receive combination therapy with VIR-3434 + TDF for 44 weeks total THRIVE: Cohort 2b (VIR-3434 + VIR-2218 + TDF) VIR-2218 Participants will receive combination therapy with VIR-3434 + VIR-2218 + TDF for 44 weeks total THRIVE: Cohort 2b (VIR-3434 + VIR-2218 + TDF) TDF Participants will receive combination therapy with VIR-3434 + VIR-2218 + TDF for 44 weeks total STRIVE: Cohort 3a (VIR-3434 + TDF) VIR-3434 Participants will receive combination therapy with VIR-3434 + TDF for 36 or 40 weeks total STRIVE: Cohort 3a (VIR-3434 + TDF) TDF Participants will receive combination therapy with VIR-3434 + TDF for 36 or 40 weeks total STRIVE: Cohort 4a (VIR-3434 + VIR-2218 + TDF) VIR-3434 Participants will receive combination therapy with VIR-3434 + VIR-2218 + TDF for 20 or 44 weeks total THRIVE: Cohort 2b (VIR-3434 + VIR-2218 + TDF) VIR-3434 Participants will receive combination therapy with VIR-3434 + VIR-2218 + TDF for 44 weeks total STRIVE: Cohort 4a (VIR-3434 + VIR-2218 + TDF) TDF Participants will receive combination therapy with VIR-3434 + VIR-2218 + TDF for 20 or 44 weeks total STRIVE: Cohort 5a (VIR-3434 + VIR-2218 + TDF + PEG-IFNα) TDF Participants will receive combination therapy with VIR-3434 + VIR-2218 +TDF + PEG-IFNα for 48 weeks total STRIVE: Cohort 5a (VIR-3434 + VIR-2218 + TDF + PEG-IFNα) PEG-IFNα Participants will receive combination therapy with VIR-3434 + VIR-2218 +TDF + PEG-IFNα for 48 weeks total THRIVE: Cohort 1b (VIR-3434 + TDF) VIR-3434 Participants will receive combination therapy with VIR-3434 + TDF for 44 weeks STRIVE: Cohort 5a (VIR-3434 + VIR-2218 + TDF + PEG-IFNα) VIR-3434 Participants will receive combination therapy with VIR-3434 + VIR-2218 +TDF + PEG-IFNα for 48 weeks total STRIVE: Cohort 4a (VIR-3434 + VIR-2218 + TDF) VIR-2218 Participants will receive combination therapy with VIR-3434 + VIR-2218 + TDF for 20 or 44 weeks total STRIVE: Cohort 5a (VIR-3434 + VIR-2218 + TDF + PEG-IFNα) VIR-2218 Participants will receive combination therapy with VIR-3434 + VIR-2218 +TDF + PEG-IFNα for 48 weeks total STRIVE: Cohort 2a (VIR-3434 + TDF) TDF Participants will receive combination therapy with VIR-3434 + TDF for 44 weeks total THRIVE: Cohort 1b (VIR-3434 + TDF) TDF Participants will receive combination therapy with VIR-3434 + TDF for 44 weeks
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 and THRIVE: Proportion of participants with serum HBsAg ≤ 10 IU/mL at end of treatment Up to 48 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: 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 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
Trial Locations
- Locations (1)
Investigative Site
🇬🇧Manchester, United Kingdom