What side effects are associated with this type of intervention?

For RNA interference treatments like VIR-2218, common side effects may include injection site reactions, flu-like symptoms, and potential liver enzyme elevations. Monoclonal antibodies such as VIR-3434 can cause infusion-related reactions, including fever, chills, and allergic reactions. PEG-IFNα, an immune system booster, is associated with flu-like symptoms, fatigue, depression, and hematologic abnormalities such as neutropenia and thrombocytopenia. These side effects vary in severity and frequency among patients.

What prior FDA approvals exist?

The FDA has approved several treatments for Chronic Hepatitis B, including pegylated interferon-alpha (PEG-IFNα), which boosts the immune system and has shown effectiveness in HBeAg-positive patients. Antiviral drugs such as entecavir and tenofovir disoproxil fumarate have also been approved, exhibiting potent viral inhibitory effects. While RNA interference agents like VIR-2218 and monoclonal antibodies like VIR-3434 are still under investigation, they represent promising new approaches targeting HBV mRNA and surface antigens, respectively.

What other types of research exist?

Promising novel alternatives for Chronic Hepatitis B treatment include: 1) Tenofovir alafenamide (TAF) - a nucleotide reverse transcriptase inhibitor with improved safety profile over tenofovir disoproxil fumarate (TDF). 2) REP 2139 - a nucleic acid polymer that inhibits HBV subviral particle assembly and secretion, showing high rates of HBsAg loss/seroconversion. 3) Combination therapies involving nucleos(t)ide analogues and PegIFN, which have shown improved outcomes in HBeAg loss and HBsAg loss compared to monotherapy.

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Interferon

VIR-2218 + VIR-3434 + PEG-IFNα for Chronic Hepatitis B (MARCH Trial)

Verified Trial

Phase 2

Recruiting

Research Sponsored by Vir Biotechnology, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

You have been diagnosed with Chronic Hepatitis B

Have you been diagnosed with chronic hepatitis B virus infection for at least 6 months?

Must not have

Have you taken any interferon-containing therapy (for example, Pegasys or Peg-Intron) within the past 12 months?

Have you had major surgery within the past 3 months?

Timeline

Screening 60 days

Treatment 24 weeks

Follow Up 48 weeks

Awards & highlights

No Placebo-Only Group

Summary

This trial involves testing three treatments (VIR-2218, VIR-3434, and PEG-IFNα) on patients with chronic hepatitis B. The goal is to see if these treatments are safe, can be tolerated by patients, and are effective in reducing the virus. The treatments work by either lowering the virus levels or boosting the immune system to fight the virus. Peginterferon alpha (PEG-IFNα) has been used to treat chronic hepatitis B by modulating the immune system, often in combination with other medications for enhanced efficacy.

Who is the study for?

This trial is for men and women aged 18 to 65 with chronic hepatitis B infection lasting at least 6 months, who have been on NRTI therapy for over two months. It's not suitable for those with significant liver damage, history of severe allergic reactions to monoclonal antibodies or interferons, other chronic liver diseases, substance abuse issues, or certain medical conditions.

What is being tested?

The study tests the safety and effectiveness of VIR-2218, VIR-3434, and/or PEG-IFNα in treating chronic hepatitis B. Participants will receive one or more of these treatments as part of a phase 2 clinical trial designed to evaluate how well they work and how safe they are.

What are the potential side effects?

Potential side effects may include typical reactions related to immune system activation such as flu-like symptoms from PEG-IFNα; infusion-related reactions; possible organ inflammation due to antibody treatment; fatigue; and allergic responses.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Timeline

Screening ~ 60 days0 visits

Treatment ~ 24 weeks0 visits

Follow Up ~ 48 weeks0 visits

Screening ~ 60 days

Treatment ~ 24 weeks

Follow Up ~48 weeks

This trial's timeline: 60 days for screening, 24 weeks for treatment, and 48 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Proportion of subjects with HBsAg loss at 24 weeks post-end of treatment

Proportion of subjects with HBsAg loss at end of treatment

Proportion of subjects with serious adverse events (SAEs)

+1 more

Secondary study objectives

%AUCexp

AUCinf

AUClast

+20 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

12Treatment groups

Experimental Treatment

Group I: Cohort 8a (VIR-2218 + VIR-3434)Experimental Treatment2 Interventions

Subjects will receive multiple doses of VIR-2218 + VIR-3434 for 20 weeks

Group II: Cohort 7a (VIR-2218 + VIR-3434)Experimental Treatment2 Interventions

Subjects will receive multiple doses of VIR-2218 + VIR-3434 for 44 weeks

Group III: Cohort 6a (VIR-2218 + VIR-3434)Experimental Treatment2 Interventions

Subjects will receive multiple doses of VIR-2218 + VIR-3434 for 11 weeks

Group IV: Cohort 5a (VIR-2218 + VIR-3434)Experimental Treatment2 Interventions

Subjects will receive multiple doses of VIR-2218 + VIR-3434 for 11 weeks

Group V: Cohort 4a (VIR-2218 + VIR-3434)Experimental Treatment2 Interventions

Subjects will receive multiple doses of VIR-2218 + VIR-3434 for 4 weeks

Group VI: Cohort 3a (VIR-2218 + VIR-3434)Experimental Treatment2 Interventions

Subjects will receive multiple doses of VIR-2218 + VIR-3434 for 4 weeks

Group VII: Cohort 2c (VIR-2218 + VIR-3434)Experimental Treatment3 Interventions

Subjects will receive multiple doses of VIR-2218 + VIR-3434 + PEG-IFNα for 48 weeks

Group VIII: Cohort 2b (VIR-3434)Experimental Treatment1 Intervention

Subjects will receive multiple doses of VIR-3434 for 20 weeks

Group IX: Cohort 2a (VIR-2218 + VIR-3434)Experimental Treatment2 Interventions

Subjects will receive multiple lead-in doses of VIR-2218, then combination therapy with VIR-2218 + VIR-3434 for 20 weeks total

Group X: Cohort 1c (VIR-2218 + VIR-3434)Experimental Treatment3 Interventions

Subjects will receive multiple doses of VIR-2218 + VIR-3434 + PEG-IFNα for 24 weeks

Group XI: Cohort 1b (VIR-3434)Experimental Treatment1 Intervention

Subjects will receive multiple doses of VIR-3434 for 44 weeks

Group XII: Cohort 1a (VIR-2218 + VIR-3434)Experimental Treatment2 Interventions

Subjects will receive multiple lead-in doses of VIR-2218, then combination therapy with VIR-2218 + VIR-3434 for 20 weeks total

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

VIR-2218

2020

Completed Phase 2

~290

VIR-3434

2020

Completed Phase 1

~120

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Chronic Hepatitis B include RNA interference, monoclonal antibodies, and immune system boosters. RNA interference, such as with VIR-2218, targets and degrades HBV mRNA, reducing the production of viral proteins and replication of the virus. Monoclonal antibodies like VIR-3434 target HBV surface antigens, neutralizing the virus and preventing it from infecting new cells. PEG-IFNα boosts the immune system, enhancing the body's ability to fight off the virus. These treatments are crucial for Chronic Hepatitis B patients as they aim to reduce viral load, prevent liver damage, and improve long-term health outcomes.