VIR-2218 + VIR-3434 + PEG-IFNα for Chronic Hepatitis B

(MARCH Trial)

Not currently recruiting at 40 trial locations

Overseen By Study Inquiry

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vir Biotechnology, Inc.

Must be taking: NRTI therapy

Disqualifiers: Fibrosis, Cirrhosis, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4-48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for chronic hepatitis B, a liver infection lasting more than six months. It evaluates the effectiveness and safety of the drugs VIR-2218, VIR-3434, and PEG-IFNα (a type of interferon therapy), both individually and in combination. Participants will receive different combinations of these treatments for varying durations to identify the best approach. Suitable candidates have had chronic hepatitis B for at least six months and are already on NRTI therapy, which helps control the virus. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to advancing hepatitis B treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that you have been on NRTI therapy (a type of medication for hepatitis B) for at least 2 months before joining.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using VIR-2218 and VIR-3434 together, with or without PEG-IFNα (a medication often used for viral infections), is generally safe and well tolerated by people with chronic hepatitis B. In earlier studies, some side effects appeared, but they were mostly mild and manageable.

VIR-2218 has lowered the amount of the virus in the body, indicating its safety and effectiveness. VIR-3434 has also helped control the virus, with evidence supporting its safety.

When combined with PEG-IFNα, these treatments are generally safe, with most side effects being non-serious. However, PEG-IFNα can sometimes cause flu-like symptoms, which is important for potential trial participants to consider.

This trial is in phase 2, indicating it has passed initial safety checks. While this provides some confidence in its safety, ongoing studies will further clarify any potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for chronic hepatitis B, like antivirals and interferons, aim to suppress the virus but often don't lead to a cure. Researchers are excited about the combination of VIR-2218, VIR-3434, and PEG-IFNα because they work differently. VIR-2218 is a small interfering RNA that targets the virus's genetic material, aiming to reduce the virus's ability to reproduce. VIR-3434 is a monoclonal antibody that can neutralize the virus and boost the immune system's response. This novel approach could potentially offer a more effective and lasting solution for chronic hepatitis B compared to existing options.

What evidence suggests that this trial's treatments could be effective for chronic hepatitis B?

Research has shown that using VIR-2218 and VIR-3434 together can significantly lower hepatitis B surface antigen (HBsAg) levels by 2.7-3.1 log10 IU/mL by the end of treatment. This trial includes arms where participants receive both VIR-2218 and VIR-3434, marking a hopeful step toward a functional cure for chronic hepatitis B. Other trial arms will study VIR-3434 alone, a neutralizing antibody that reduces HBsAg levels by blocking the virus from entering cells and decreasing HBsAg in the blood. Additionally, VIR-2218 is well-tolerated and has antiviral effects that may contribute to achieving a functional cure. Together, these treatments enhance each other's ability to lower HBsAg levels, making them a strong option for managing chronic hepatitis B. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

You have been diagnosed with Chronic Hepatitis B

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

Have been on stable nucleoside/nucleotide analogue (NA) treatment (for example, tenofovir or entecavir) for the last 6 months?

Exclusion Criteria

Have you had major surgery within the past 3 months?

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

You have been diagnosed with Liver Disease

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple doses of VIR-2218, VIR-3434, and/or PEG-IFNα

4-48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PEG-IFNα
• VIR-2218
• VIR-3434

Trial Overview

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.

How Is the Trial Designed?

Group I: Cohort 8a (VIR-2218 + VIR-3434) Experimental Treatment 2 Interventions

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

Group II: Cohort 7a (VIR-2218 + VIR-3434) Experimental Treatment 2 Interventions

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

Group III: Cohort 6a (VIR-2218 + VIR-3434) Experimental Treatment 2 Interventions

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

Group IV: Cohort 5a (VIR-2218 + VIR-3434) Experimental Treatment 2 Interventions

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

Group V: Cohort 4a (VIR-2218 + VIR-3434) Experimental Treatment 2 Interventions

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

Group VI: Cohort 3a (VIR-2218 + VIR-3434) Experimental Treatment 2 Interventions

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

Group VII: Cohort 2c (VIR-2218 + VIR-3434 + PEG-IFNα) Experimental Treatment 3 Interventions

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

Group VIII: Cohort 2b (VIR-3434) Experimental Treatment 1 Intervention

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

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

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

Group X: Cohort 1d (VIR-3434 + PEG-IFNα) Experimental Treatment 2 Interventions

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

Group XI: Cohort 1c (VIR-2218 + VIR-3434 + PEG-IFNα) Experimental Treatment 3 Interventions

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

Group XII: Cohort 1b (VIR-3434) Experimental Treatment 1 Intervention

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

Group XIII: Cohort 1a (VIR-2218 + VIR-3434) Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

Vir Biotechnology, Inc.

Lead Sponsor

Trials

30

Recruited

13,300+

Published Research Related to This Trial

In a study of 47 patients with HBeAg-positive chronic hepatitis B, treatment with peginterferon α-2a combined with either lamivudine or adefovir for 96 weeks resulted in a high rate of hepatitis B virus suppression, with all patients achieving HBV DNA levels below 500 copies/mL.

The study also showed significant rates of HBeAg seroconversion, increasing from 46.8% at 48 weeks to 74.5% at 96 weeks, indicating that this treatment strategy is effective for achieving long-term immune response against the virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended treatment with peginterferon α-2a in combination with lamivudine or adefovir for 96 weeks yields high rates of HBeAg and HBsAg seroconversion. Cao, ZH., Ma, LN., Zhang, HW., et al.[2018]

In a study of 16 HBeAg-positive hepatitis B patients with lamivudine resistance, pegylated interferon-alpha treatment resulted in a 12.5% seroconversion rate, indicating limited efficacy in this resistant population.

Despite a significant reduction in viral load during treatment, levels rebounded after cessation, suggesting that pegylated interferon-alpha may only be beneficial for patients with low levels of mutant virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of pegylated interferon-alpha on the treatment of lamivudine resistant chronic HBeAg positive hepatitis B virus infection. Leemans, WF., Flink, HJ., Janssen, HL., et al.[2018]

In a study of 160 HBeAg-negative chronic hepatitis B patients treated with pegylated interferons, 25% achieved a sustained virologic response (SVR), indicating the treatment's efficacy.

Key predictors for achieving SVR included a decline of 1 log10 IU/mL in viral load after the first month and a serum HBV DNA level below 2,000 IU/mL by the third month of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of response to pegylated interferon treatment in HBeAg-negative patients with chronic hepatitis B. Guclu, E., Tuna, N., Karabay, O., et al.[2018]

In a study of 72 patients with chronic hepatitis B, PEG-IFN alpha-2a demonstrated significantly higher rates of HBeAg negative cases and lower HBV DNA levels compared to the control group receiving standard interferon alpha after 48 weeks of treatment.

PEG-IFN alpha-2a not only effectively inhibited HBV replication but also showed lasting effects after treatment, with no significant changes in liver inflammation or fibrosis, and was well tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pegylated interferon alpha 2a in treating chronic hepatitis B patients]. Tian, YL., Zhao, W., Shen, L., et al.[2018]

In a study of 218 treatment-naive Chinese patients with HBeAg-positive chronic hepatitis B, the combination of pegylated interferon alfa-2a and entecavir did not show superior efficacy compared to peg-IFN monotherapy, with similar rates of HBeAg seroconversion across all treatment groups.

All treatment groups achieved significant reductions in HBeAg levels, but while the ETV add-on showed greater reductions in hepatitis B virus DNA during treatment, these effects were not sustained after treatment ended, indicating that the optimal treatment strategy remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, open-label clinical study of combined pegylated interferon Alfa-2a (40KD) and entecavir treatment for hepatitis B "e" antigen-positive chronic hepatitis B. Xie, Q., Zhou, H., Bai, X., et al.[2022]

Citations

1.

investors.vir.bio

investors.vir.bio/news/news-details/2023/Vir-Biotechnology-Presents-New-Data-Evaluating-the-Potential-for-VIR-2218-and-VIR-3434-as-Therapies-for-Chronic-Hepatitis-B-and-Hepatitis-D-06-24-2023/default.aspx

News Details

As previously shown, the combination of VIR-2218 and VIR-3434 resulted in a 2.7-3.1 log10 IU/mL decline in HBsAg levels at the end of treatment.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04856085?term=AREA%5BConditionSearch%5D(Hepatitis%20B)%20AND%20AREA%5BInterventionSearch%5D(VIR-3434)&rank=2

NCT04856085 | Study of VIR-2218, VIR-3434, and/or PEG- ...

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 ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10989302/

A comprehensive review of phases II and III therapeutic ...

In fact, most participants were able to achieve an HBsAg level < 10 IU/mL. VIR-3434 has an additive effect to VIR-2218 in achieving a greater HBsAg reduction ...

4.

natap.org

natap.org/2021/HBV/102021_02.htm

Vir Biotechnology Initiates Phase 2 Clinical Trial Evaluating ...

The multi-center, open-label Phase 2 trial is designed to evaluate the safety, tolerability and efficacy of the combination of VIR-2218 and VIR-3434 in ...

5.

s203.q4cdn.com

s203.q4cdn.com/628578897/files/doc_presentation/2023/11/Vir_AASLD-2023_Data-Analyst-Call-Presentation_FINAL.pdf

Vir Biotechnology Corporate Presentation

antiviral activity of VIR-2218 in combination with VIR-3434 in virally suppressed participants with chronic. HBV infection who received ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39389081/

VIR-2218 (elebsiran) plus pegylated interferon-alfa-2a in ...

VIR-2218 (elebsiran), a small interfering RNA agent against HBV transcripts, reduces HBsAg concentrations. We aimed to evaluate the safety and ...

7.

s203.q4cdn.com

s203.q4cdn.com/628578897/files/doc_presentations/2024/Jun/EASL-2024_Hepatic-Impairment-Print-and-ePoster_Final-Submitted.pdf

Pharmacokinetics and Safety of Single Dose of the ...

The monoclonal antibody VIR-3434 and siRNA VIR-2218 for the treatment of chronic Hepatitis D. Virus: preliminary results from the Phase 2 ...