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

Hepatitis B, Chronic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05612581
• Other study ID #: VIR-MHB1-V200
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: May 10, 2023
• Est. completion date: March 2027

Study information

• Verified date: February 2024
• Source: Vir Biotechnology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: March 2027
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 66 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
France	Investigative Site	Clichy
France	Investigative Site	Nice
France	Investigative Site	Rennes
France	Investigative Site	Toulouse
Hong Kong	Investigative Site	Hong Kong	Sha Tin
Hong Kong	Investigative Site	Hong Kong
Korea, Republic of	Investigative Site	Busan
Korea, Republic of	Investigative Site	Seoul
Korea, Republic of	Investigative Site	Yangsan
Moldova, Republic of	Investigative Site	Chisinau
Romania	Investigative Site	Bucharest
United Kingdom	Investigative Site	Glasgow
United Kingdom	Investigative Site	London
United Kingdom	Investigative Site	London
United Kingdom	Investigative Site	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Vir Biotechnology, Inc.

Countries where clinical trial is conducted

France,  Hong Kong,  Korea, Republic of,  Moldova, Republic of,  Romania,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	STRIVE and THRIVE: Proportion of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)		Up to 96 weeks
Secondary	STRIVE and THRIVE: Proportion of participants with serum HBsAg = 10 IU/mL at end of treatment		Up to 48 weeks
Secondary	STRIVE and THRIVE: Proportion of participants with serum HBsAg = 10 IU/mL at 24 weeks post-end of treatment		Up to 72 weeks
Secondary	STRIVE and THRIVE: Serum HBsAg levels and change from baseline across timepoints in the study		Up to 96 weeks
Secondary	STRIVE and THRIVE: Serum HBsAg level at nadir during the study		Up to 96 weeks
Secondary	STRIVE and THRIVE: Time to achieve nadir of serum HBsAg during the study		Up to 96 weeks
Secondary	STRIVE and THRIVE: Time to achieve serum HBsAg loss (< 0.05 IU/mL)		Up to 96 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	STRIVE: For HBeAg-positive participants: proportion of participants with HBeAg loss (undetectable HBeAg) and/or anti-HBe seroconversion		Up to 72 weeks
Secondary	STRIVE: Incidence and titers of anti-drug antibodies (ADA; if applicable) to VIR-3434		Up to 96 weeks
Secondary	STRIVE: Mean change in serum HBsAg level from baseline across timepoints in the study		Up to 96 weeks
Secondary	STRIVE: Proportion of participants achieving HBV DNA (< LLOQ) across timepoints in the study		Up to 96 weeks
Secondary	STRIVE: Proportion of participants achieving ALT = ULN across timepoints in the study		Up to 96 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	THRIVE: Incidence and titers of ADA (if applicable) to VIR-3434		Up to 92 weeks
Secondary	THRIVE: Mean change in serum HBsAg level from baseline across timepoints in the study		Up to 92 weeks
Secondary	THRIVE: Proportion of participants achieving HBV DNA (< LLOQ)		Up to 92 weeks