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Study of VIR-2218, VIR-3434, And/or PEG-IFNα in Subjects with Chronic Hepatitis B Virus Infection

Phase 2
Active, not recruiting
Conditions
Hepatitis B, Chronic
Interventions
Registration Number
NCT04856085
Lead Sponsor
Vir Biotechnology, Inc.
Brief Summary

This is a phase 2 study in which participants with chronic hepatitis B virus (HBV) infection will receive VIR-2218, VIR-3434 and/or PEG-IFNα and be assessed for safety, tolerability, and efficacy

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
244
Inclusion Criteria
  • Male or female ages 18 - <66 years
  • Chronic HBV infection for >/= 6 months
  • On NRTI therapy for >/= 2 months at the time of screening
Exclusion Criteria
  • Any clinically significant chronic or acute medical condition that makes the participant unsuitable for participation
  • Significant fibrosis or cirrhosis
  • History or evidence of drug or alcohol abuse
  • History of chronic liver disease from any cause other than chronic HBV infection
  • History of hepatic decompensation
  • History of anaphylaxis
  • History of allergic reactions, hypersensitivity, or intolerance to monoclonal antibodies, antibody fragments, or any excipients of VIR-3434
  • History of immune complex disease
  • History of known contraindication to any interferon product

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort 2a (VIR-2218 + VIR-3434)VIR-2218Participants will receive multiple lead-in doses of VIR-2218, then combination therapy with VIR-2218 + VIR-3434 for 20 weeks total
Cohort 5a (VIR-2218 + VIR-3434)VIR-3434Participants will receive multiple doses of VIR-2218 + VIR-3434 for 11 weeks
Cohort 1d (VIR-3434 + PEG-IFNα)PEG-IFNαParticipants will receive multiple doses of VIR-3434 + PEG-IFNα for 48 weeks
Cohort 1c (VIR-2218 + VIR-3434 + PEG-IFNα)PEG-IFNαParticipants will receive multiple doses of VIR-2218 + VIR-3434 + PEG-IFNα for 24 weeks
Cohort 1a (VIR-2218 + VIR-3434)VIR-3434Participants will receive multiple lead-in doses of VIR-2218, then combination therapy with VIR-2218 + VIR-3434 for 20 weeks total
Cohort 2c (VIR-2218 + VIR-3434 + PEG-IFNα)PEG-IFNαParticipants will receive multiple doses of VIR-2218 + VIR-3434 + PEG-IFNα for 48 weeks
Cohort 3a (VIR-2218 + VIR-3434)VIR-2218Participants will receive multiple doses of VIR-2218 + VIR-3434 for 4 weeks
Cohort 5a (VIR-2218 + VIR-3434)VIR-2218Participants will receive multiple doses of VIR-2218 + VIR-3434 for 11 weeks
Cohort 4a (VIR-2218 + VIR-3434)VIR-2218Participants will receive multiple doses of VIR-2218 + VIR-3434 for 4 weeks
Cohort 6a (VIR-2218 + VIR-3434)VIR-2218Participants will receive multiple doses of VIR-2218 + VIR-3434 for 11 weeks
Cohort 7a (VIR-2218 + VIR-3434)VIR-2218Participants will receive multiple doses of VIR-2218 + VIR-3434 for 44 weeks
Cohort 2c (VIR-2218 + VIR-3434 + PEG-IFNα)VIR-2218Participants will receive multiple doses of VIR-2218 + VIR-3434 + PEG-IFNα for 48 weeks
Cohort 8a (VIR-2218 + VIR-3434)VIR-2218Participants will receive multiple doses of VIR-2218 + VIR-3434 for 20 weeks
Cohort 1c (VIR-2218 + VIR-3434 + PEG-IFNα)VIR-2218Participants will receive multiple doses of VIR-2218 + VIR-3434 + PEG-IFNα for 24 weeks
Cohort 1a (VIR-2218 + VIR-3434)VIR-2218Participants will receive multiple lead-in doses of VIR-2218, then combination therapy with VIR-2218 + VIR-3434 for 20 weeks total
Cohort 2a (VIR-2218 + VIR-3434)VIR-3434Participants will receive multiple lead-in doses of VIR-2218, then combination therapy with VIR-2218 + VIR-3434 for 20 weeks total
Cohort 3a (VIR-2218 + VIR-3434)VIR-3434Participants will receive multiple doses of VIR-2218 + VIR-3434 for 4 weeks
Cohort 4a (VIR-2218 + VIR-3434)VIR-3434Participants will receive multiple doses of VIR-2218 + VIR-3434 for 4 weeks
Cohort 1b (VIR-3434)VIR-3434Participants will receive multiple doses of VIR-3434 for 44 weeks
Cohort 6a (VIR-2218 + VIR-3434)VIR-3434Participants will receive multiple doses of VIR-2218 + VIR-3434 for 11 weeks
Cohort 7a (VIR-2218 + VIR-3434)VIR-3434Participants will receive multiple doses of VIR-2218 + VIR-3434 for 44 weeks
Cohort 8a (VIR-2218 + VIR-3434)VIR-3434Participants will receive multiple doses of VIR-2218 + VIR-3434 for 20 weeks
Cohort 2b (VIR-3434)VIR-3434Participants will receive multiple doses of VIR-3434 for 20 weeks
Cohort 1c (VIR-2218 + VIR-3434 + PEG-IFNα)VIR-3434Participants will receive multiple doses of VIR-2218 + VIR-3434 + PEG-IFNα for 24 weeks
Cohort 2c (VIR-2218 + VIR-3434 + PEG-IFNα)VIR-3434Participants will receive multiple doses of VIR-2218 + VIR-3434 + PEG-IFNα for 48 weeks
Cohort 1d (VIR-3434 + PEG-IFNα)VIR-3434Participants will receive multiple doses of VIR-3434 + PEG-IFNα for 48 weeks
Primary Outcome Measures
NameTimeMethod
Proportion of participants with treatment-emergent adverse events (TEAEs)Up to 72 weeks
Proportion of participants with serious adverse events (SAEs)Up to 72 weeks
Proportion of participants with hepatitis B surface antigen (HBsAg) loss (defined as undetectable HBsAg) at end of treatmentUp to 48 weeks
Proportion of participants with HBsAg loss (defined as undetectable HBsAg) at 24 weeks post-end of treatmentUp to 72 weeks
Secondary Outcome Measures
NameTimeMethod
Time to achieve serum HBsAg lossUp to 110 weeks
Proportion of participants meeting criteria for NRTI retreatmentUp to 110 weeks
Absolute serum HBsAg and change from baseline across all timepoints in the studyUp to 110 weeks
For hepatitis B e-antigen (HBeAg)-positive participants: Proportion of participants with HBeAg loss (undetectable HBeAg) and/or anti-HBe seroconversion at any timepointUp to 110 weeks
For HBeAg-positive participants: Time to HBeAg loss (undetectable HBeAg) and/or anti-HBe seroconversionUp to 110 weeks
TmaxUp to 110 weeks
Nadir and maximum reduction of serum HBsAg from baselineUp to 110 weeks
ClastUp to 110 weeks
TlastUp to 110 weeks
t1/2Up to 110 weeks
λzUp to 110 weeks
CmaxUp to 110 weeks
AUCinfUp to 110 weeks
AUClastUp to 110 weeks
Proportion of participants achieving sustained suppression of HBV DNA (< lower limit of quantification (LLOQ) for >= 24 weeks after discontinuation of all treatment, including NRTIs)Up to 110 weeks
%AUCexpUp to 110 weeks
Vz/FUp to 110 weeks
CL/FUp to 110 weeks
Number of participants with incidence and titers of anti-drug antibody (ADA) (if applicable) to VIR-3434Up to 110 weeks
Proportion of participants meeting criteria for nucleotide reverse transcriptase inhibitors (NRTI) discontinuationUp to 60 weeks
Proportion of participants achieving undetectable HBsAg and sustained suppression of HBV DNA [below the LLOQ, target not detected (TND)] >/= 24 weeks after discontinuation of all treatment, including NRTIsUp to 110 weeks
Proportion of participants with serum HBsAg < 10 IU/mL at end of treatmentUp to 48 weeks
Proportion of participants with anti-HBs seroconversionUp to 110 weeks
Proportion of participants with serum HBsAg < 10 IU/mL at 24 weeks post-end of treatmentUp to 72 weeks

48 weeks treatment + 24 weeks post-end of treatment

Time to achieve nadir of serum HBsAgUp to 110 weeks

Trial Locations

Locations (1)

Investigative Site

🇬🇧

Manchester, United Kingdom

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