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

Sponsor

Vir Biotechnology, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05612581

Collaborator

(none)

150

Enrollment

Locations

Arms

51.7

Anticipated Duration (Months)

Patients Per Site

1.5

Patients Per Site Per Month

Study Details

Study Description

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 HBV infection.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B, Chronic	Drug: VIR-3434 Drug: VIR-2218 Drug: TDF Drug: PEG-IFNα	Phase 1/Phase 2

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, PEG-IFNα, and NRTI in noncirrhotic adult participants with chronic HBV infection that have not received prior NRTI or PEG-IFNα 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 Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 9, 2022

Anticipated Primary Completion Date :

Mar 1, 2026

Anticipated Study Completion Date :

Mar 1, 2027

Arms and Interventions

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 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 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 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-3434 VIR-3434 given by subcutaneous injection Drug: VIR-2218 VIR-2218 given by subcutaneous injection 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-3434 VIR-3434 given by subcutaneous injection Drug: VIR-2218 VIR-2218 given by subcutaneous injection Drug: TDF TDF given orally Drug: PEG-IFNα PEG-IFNα given by subcutaneous injection
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 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-3434 VIR-3434 given by subcutaneous injection Drug: VIR-2218 VIR-2218 given by subcutaneous injection Drug: TDF TDF given orally

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 66 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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