Clinical trial NCT05612581: A Platform Study to Evaluate Investigational Therapies in Chronic Hepatitis B Infection
Official title: A Platform Study Evaluating the Efficacy and Safety of Investigational Therapies in Participants With Chronic Hepatitis B Infection (PREVAIL)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hepatitis B, Chronic
Keywords: Hepatitis B Virus
Chronic Hepatitis B
HBV
Hepatitis
Lead sponsor: Vir Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2022-11-10
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 66
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: STRIVE and THRIVE: Proportion of participants achieving suppression of HBV DNA (< LLOQ) with HBsAg loss (< 0.05 IU/mL) at the end of treatment
timeFrame: Up to 72 weeks
Secondary outcomes:
measure: STRIVE and THRIVE: Proportion of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
timeFrame: Up to 96 weeks
measure: STRIVE and THRIVE: Proportion of participants with serum HBsAg ≤ 10 IU/mL at end of treatment
timeFrame: Up to 48 weeks
measure: STRIVE and THRIVE: Proportion of participants with serum HBsAg ≤ 10 IU/mL at 24 weeks post-end of treatment
timeFrame: Up to 72 weeks
measure: STRIVE and THRIVE: Serum HBsAg levels and change from baseline across timepoints in the study
timeFrame: Up to 96 weeks
measure: STRIVE and THRIVE: Serum HBsAg level at nadir during the study
timeFrame: Up to 96 weeks
measure: STRIVE and THRIVE: Time to achieve nadir of serum HBsAg during the study
timeFrame: Up to 96 weeks
measure: STRIVE and THRIVE: Time to achieve serum HBsAg loss (< 0.05 IU/mL)
timeFrame: Up to 96 weeks
measure: 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
timeFrame: Up to 76 weeks
measure: 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
timeFrame: Up to 96 weeks
measure: STRIVE: Proportion of participants with HBsAg loss (<0.05 IU/mL) at end of treatment and at 24 weeks post-end of treatment
timeFrame: Up to 72 weeks
measure: 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
timeFrame: Up to 96 weeks
measure: STRIVE: For HBeAg-positive participants: proportion of participants with HBeAg loss (undetectable HBeAg) and/or anti-HBe seroconversion
timeFrame: Up to 72 weeks
measure: STRIVE: Incidence and titers of anti-drug antibodies (ADA; if applicable) to VIR-3434
timeFrame: Up to 96 weeks
measure: STRIVE: Mean change in serum HBsAg level from baseline across timepoints in the study
timeFrame: Up to 96 weeks
measure: STRIVE: Proportion of participants achieving HBV DNA (< LLOQ) across timepoints in the study
timeFrame: Up to 96 weeks
measure: STRIVE: Proportion of participants achieving ALT ≤ ULN across timepoints in the study
timeFrame: Up to 96 weeks
measure: 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
timeFrame: Up to 92 weeks
measure: THRIVE: Proportion of participants achieving HBsAg loss (< 0.05 IU/mL) at end of treatment and at 24 weeks post-end of treatment
timeFrame: Up to 44 weeks
measure: THRIVE: Proportion of participants achieving sustained suppression of HBV DNA (< LLOQ) after discontinuation of all treatment at 24 weeks and at 48 weeks
timeFrame: Up to 68 weeks
measure: THRIVE: Incidence and titers of ADA (if applicable) to VIR-3434
timeFrame: Up to 92 weeks
measure: THRIVE: Mean change in serum HBsAg level from baseline across timepoints in the study
timeFrame: Up to 92 weeks
measure: THRIVE: Proportion of participants achieving HBV DNA (< LLOQ)
timeFrame: Up to 92 weeks
Other outcomes:
Locations:
city: Clichy
country: France
facility: Investigative Site
city: Nice
country: France
facility: Investigative Site
city: Rennes
country: France
facility: Investigative Site
city: Toulouse
country: France
facility: Investigative Site
city: Hong Kong
country: Hong Kong
facility: Investigative Site
state: Sha Tin
city: Hong Kong
country: Hong Kong
facility: Investigative Site
city: Busan
country: Korea, Republic of
facility: Investigative Site
city: Seoul
country: Korea, Republic of
facility: Investigative Site
city: Yangsan
country: Korea, Republic of
facility: Investigative Site
city: Chisinau
country: Moldova, Republic of
facility: Investigative Site
city: Bucharest
country: Romania
facility: Investigative Site
city: Glasgow
country: United Kingdom
facility: Investigative Site
city: London
country: United Kingdom
facility: Investigative Site
city: London
country: United Kingdom
facility: Investigative Site
city: Manchester
country: United Kingdom
facility: Investigative Site
Study officials:
References: