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

Study Overview
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Brief Summary
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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

Official Title
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A Phase 2 Study to Evaluate the Safety, Tolerability, and Efficacy of Regimens Containing VIR-2218, VIR-3434, and/or PEG-IFNα in Subjects With Chronic Hepatitis B Virus Infection

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Drug: VIR-2218
* Drug: VIR-3434
* Drug: PEG-IFNα


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1a (VIR-2218 + VIR-3434)<br>Participants will receive multiple lead-in doses of VIR-2218, then combination therapy with VIR-2218 + VIR-3434 for 20 weeks total | Drug: VIR-2218<br>* VIR-2218 given by subcutaneous injection<br>Drug: VIR-3434<br>* VIR-3434 given by subcutaneous injection<br>|
| Experimental: Cohort 2a (VIR-2218 + VIR-3434)<br>Participants will receive multiple lead-in doses of VIR-2218, then combination therapy with VIR-2218 + VIR-3434 for 20 weeks total | Drug: VIR-2218<br>* VIR-2218 given by subcutaneous injection<br>Drug: VIR-3434<br>* VIR-3434 given by subcutaneous injection<br>|
| Experimental: Cohort 3a (VIR-2218 + VIR-3434)<br>Participants will receive multiple doses of VIR-2218 + VIR-3434 for 4 weeks | Drug: VIR-2218<br>* VIR-2218 given by subcutaneous injection<br>Drug: VIR-3434<br>* VIR-3434 given by subcutaneous injection<br>|
| Experimental: Cohort 4a (VIR-2218 + VIR-3434)<br>Participants will receive multiple doses of VIR-2218 + VIR-3434 for 4 weeks | Drug: VIR-2218<br>* VIR-2218 given by subcutaneous injection<br>Drug: VIR-3434<br>* VIR-3434 given by subcutaneous injection<br>|
| Experimental: Cohort 5a (VIR-2218 + VIR-3434)<br>Participants will receive multiple doses of VIR-2218 + VIR-3434 for 11 weeks | Drug: VIR-2218<br>* VIR-2218 given by subcutaneous injection<br>Drug: VIR-3434<br>* VIR-3434 given by subcutaneous injection<br>|
| Experimental: Cohort 6a (VIR-2218 + VIR-3434)<br>Participants will receive multiple doses of VIR-2218 + VIR-3434 for 11 weeks | Drug: VIR-2218<br>* VIR-2218 given by subcutaneous injection<br>Drug: VIR-3434<br>* VIR-3434 given by subcutaneous injection<br>|
| Experimental: Cohort 7a (VIR-2218 + VIR-3434)<br>Participants will receive multiple doses of VIR-2218 + VIR-3434 for 44 weeks | Drug: VIR-2218<br>* VIR-2218 given by subcutaneous injection<br>Drug: VIR-3434<br>* VIR-3434 given by subcutaneous injection<br>|
| Experimental: Cohort 8a (VIR-2218 + VIR-3434)<br>Participants will receive multiple doses of VIR-2218 + VIR-3434 for 20 weeks | Drug: VIR-2218<br>* VIR-2218 given by subcutaneous injection<br>Drug: VIR-3434<br>* VIR-3434 given by subcutaneous injection<br>|
| Experimental: Cohort 1b (VIR-3434)<br>Participants will receive multiple doses of VIR-3434 for 44 weeks | Drug: VIR-3434<br>* VIR-3434 given by subcutaneous injection<br>|
| Experimental: Cohort 2b (VIR-3434)<br>Participants will receive multiple doses of VIR-3434 for 20 weeks | Drug: VIR-3434<br>* VIR-3434 given by subcutaneous injection<br>|
| Experimental: Cohort 1c (VIR-2218 + VIR-3434 + PEG-IFNα)<br>Participants will receive multiple doses of VIR-2218 + VIR-3434 + PEG-IFNα for 24 weeks | Drug: VIR-2218<br>* VIR-2218 given by subcutaneous injection<br>Drug: VIR-3434<br>* VIR-3434 given by subcutaneous injection<br>Drug: PEG-IFNα<br>* PEG-IFNα given by subcutaneous injection<br>|
| Experimental: Cohort 2c (VIR-2218 + VIR-3434 + PEG-IFNα)<br>Participants will receive multiple doses of VIR-2218 + VIR-3434 + PEG-IFNα for 48 weeks | Drug: VIR-2218<br>* VIR-2218 given by subcutaneous injection<br>Drug: VIR-3434<br>* VIR-3434 given by subcutaneous injection<br>Drug: PEG-IFNα<br>* PEG-IFNα given by subcutaneous injection<br>|
| Experimental: Cohort 1d (VIR-2218 + PEG-IFNα)<br>Participants will receive multiple doses of VIR-2218 + PEG-IFNα for 48 weeks | Drug: VIR-2218<br>* VIR-2218 given by subcutaneous injection<br>Drug: PEG-IFNα<br>* PEG-IFNα given by subcutaneous injection<br>|
| Experimental: Cohort 2d (VIR-3434 + PEG-IFNα)<br>Participants will receive multiple doses of VIR-3434 + PEG-IFNα for 48 weeks | Drug: VIR-3434<br>* VIR-3434 given by subcutaneous injection<br>Drug: PEG-IFNα<br>* PEG-IFNα given by subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with treatment-emergent adverse events (TEAEs) |  | Up to 110 weeks | 
| Proportion of participants with serious adverse events (SAEs) |  | Up to 116 weeks | 
| Proportion of participants with hepatitis B surface antigen (HBsAg) loss (defined as undetectable HBsAg) at end of treatment |  | Up to 48 weeks | 
| Proportion of participants with HBsAg loss (defined as undetectable HBsAg) at 24 weeks post-end of treatment |  | Up to 72 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute serum HBsAg and change from baseline across all timepoints in the study |  | Up to 110 weeks | 
| Nadir and maximum reduction of serum HBsAg from baseline |  | Up 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 | 
| For hepatitis B e-antigen (HBeAg)-positive participants: Proportion of participants with HBeAg loss (undetectable HBeAg) and/or anti-HBe seroconversion at any timepoint |  | Up to 110 weeks | 
| For HBeAg-positive participants: Time to HBeAg loss (undetectable HBeAg) and/or anti-HBe seroconversion |  | Up to 110 weeks | 
| Cmax |  | Up to 110 weeks | 
| Clast |  | Up to 110 weeks | 
| Tmax |  | Up to 110 weeks | 
| Tlast |  | Up to 110 weeks | 
| AUCinf |  | Up to 110 weeks | 
| AUClast |  | Up to 110 weeks | 
| %AUCexp |  | Up to 110 weeks | 
| t1/2 |  | Up to 110 weeks | 
| λz |  | Up to 110 weeks | 
| Vz/F |  | Up to 110 weeks | 
| CL/F |  | Up to 110 weeks | 
| Number of participants with incidence and titers of anti-drug antibody (ADA) (if applicable) to VIR-3434 |  | Up to 110 weeks | 
| Proportion of participants meeting criteria for nucleotide reverse transcriptase inhibitors (NRTI) discontinuation |  | Up to 60 weeks | 
| Proportion of participants meeting criteria for NRTI retreatment |  | Up to 110 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 NRTIs |  | Up to 110 weeks | 
| Proportion of participants with serum HBsAg < 10 IU/mL at end of treatment |  | Up to 48 weeks | 
| Proportion of participants with serum HBsAg < 10 IU/mL at 24 weeks post-end of treatment | 48 weeks treatment + 24 weeks post-end of treatment | Up to 72 weeks | 
| Proportion of participants with anti-HBs seroconversion |  | Up to 110 weeks | 
| Time to achieve nadir of serum HBsAg |  | Up to 110 weeks | 
| Time to achieve serum HBsAg loss |  | Up to 110 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B Virus, Chronic Hepatitis B, HBV, Hepatitis