What side effects are associated with this type of intervention?

Common treatments for liver disease, such as RNA interference therapy (e.g., VIR-2218) and monoclonal antibody therapy (e.g., VIR-3434), generally have a favorable safety profile. However, they can still cause side effects. For RNA interference therapies, side effects may include injection site reactions, fatigue, and headache. Monoclonal antibody therapies can also cause injection site reactions, as well as potential immune-related adverse effects such as allergic reactions or infections. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for liver diseases, including antiviral medications for hepatitis B and C, such as tenofovir, entecavir, and sofosbuvir. While specific FDA approvals for RNA interference therapies and monoclonal antibody therapies for liver diseases like those being studied with VIR-2218 and VIR-3434 are not detailed, these types of therapies represent advanced approaches in targeting viral components and immune modulation. RNA interference therapies aim to silence specific genes involved in disease progression, and monoclonal antibodies are designed to target and neutralize specific proteins or pathogens involved in liver diseases.

What other types of research exist?

Promising alternatives to VIR-2218 and VIR-3434 for liver disease patients include: 1) Tenofovir alafenamide (TAF) for chronic hepatitis B, which has shown non-inferiority to tenofovir disoproxil fumarate with improved renal and bone safety profiles. 2) Glecaprevir/pibrentasvir for chronic hepatitis C, which offers high cure rates across all genotypes with a shorter treatment duration. 3) Lenvatinib combined with transarterial chemoembolization (TACE) for advanced hepatocellular carcinoma, which has demonstrated improved overall survival and progression-free survival compared to lenvatinib alone.

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Antisense Oligonucleotide

VIR-2218 + VIR-3434 for Liver Cirrhosis

Phase 1

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

Must be ≥18 to ≤70 years of age at screening

All participants must have an eGFR ≥ 60 mL/min as calculated by the Modification of Diet in Renal Disease (MDRD) equation

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 18 weeks

Awards & highlights

Study Summary

This trial is testing a new drug for people with liver cirrhosis to see how it is metabolized in different degrees of impaired hepatic function compared to people with normal hepatic function.

Who is the study for?

This trial is for adults aged 18-70 with liver cirrhosis or impairment, stable health, and a BMI of 18.5-40 kg/m2. They must have a CPT score indicating mild to severe hepatic impairment but can't be on certain medications, have unstable heart conditions, active infections like HIV/HBV/HCV/HDV/HEV (with some exceptions), recent variceal bleeding, or be listed for liver transplantation.Check my eligibility

What is being tested?

The study tests the effects of single doses of VIR-2218 up to 200 mg SC or VIR-3434 at 300 mg SC alone or in combination on people with different levels of liver function as classified by the Child-Pugh-Turcotte score. It aims to understand how these drugs are processed by the body and their safety profile in those with hepatic issues.See study design

What are the potential side effects?

While specific side effects aren't listed here, common ones related to similar treatments may include injection site reactions, fatigue, nausea, potential allergic responses and possibly changes in liver enzymes which will be closely monitored during the trial.

Eligibility Criteria

Inclusion Criteria

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

Select...

I am between 18 and 70 years old.

Select...

My kidney function, measured by eGFR, is 60 mL/min or higher.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 18 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~18 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 18 weeks for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Area Under The Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast) of VIR-2218 and metabolite AS(N-1)3'VIR2218

Area Under The Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast) of VIR-3434

Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of VIR-2218 metabolite AS(N-1)3'VIR2218

+3 more

Secondary outcome measures

Incidence of ADA and titers of ADA to VIR-3434 at each study visit for cohorts receiving VIR-3434 therapy

Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

Side effects data

From 2020 Phase 1 & 2 trial • 82 Patients • NCT03672188

50%

Headache

17%

Abdominal discomfort

17%

Dry throat

17%

Upper respiratory tract infection

100%

80%

60%

40%

20%

Study treatment Arm

Part A SAD: VIR-2218 100 mg

Part B MAD: VIR-2218 20 mg

Part A SAD: VIR-2218 50 mg

Part A SAD: VIR-2218 200 mg

Part A SAD: VIR-2218 400 mg

Part A SAD: VIR-2218 600 mg

Part A SAD: VIR-2218 900 mg

Part A SAD: Placebo

Part B MAD: VIR-2218 50 mg

Part B MAD: VIR-2218 100 mg

Part B MAD: VIR-2218 200 mg

Part C MAD: VIR-2218 50 mg

Part C MAD: VIR-2218 200 mg

Part B MAD: Placebo

Part C MAD: Placebo

Trial Design

9Treatment groups

Experimental Treatment

Group I: Cohort 9: CPT-C (severe HI) and matched healthy participantsExperimental Treatment2 Interventions

This arm is optional based on Cohort 8. All participants in Cohort 9 will be receiving VIR-3434 and VIR-2218 combination therapy.

Group II: Cohort 8: CPT-B (moderate HI) and matched healthy participantsExperimental Treatment2 Interventions

All participants in Cohort 8 will be receiving VIR-3434 and VIR-2218 combination therapy.

Group III: Cohort 7: CPT-A (mild HI) and matched healthy participantsExperimental Treatment2 Interventions

All participants in Cohort 7 will be receiving VIR-3434 and VIR-2218 combination therapy.

Group IV: Cohort 6: CPT-C (severe HI) participants and matched healthy participantsExperimental Treatment1 Intervention

This arm is optional based on Cohort 5. All participants in Cohort 6 will be receiving VIR-3434 monotherapy.

Group V: Cohort 5: CPT-B (moderate HI) participants and matched healthy participantsExperimental Treatment1 Intervention

All participants in Cohort 5 will be receiving VIR-3434 monotherapy.

Group VI: Cohort 4: CPT-A (mild HI) participants and matched healthy participantsExperimental Treatment1 Intervention

All participants in Cohort 4 will be receiving VIR-3434 monotherapy.

Group VII: Cohort 3: CPT-A (mild HI) participants and matched healthy participantsExperimental Treatment1 Intervention

This cohort is optional. All participants in Cohort 3 will be receiving VIR-2218 monotherapy.

Group VIII: Cohort 2: CPT-C (severe HI) participants and matched healthy participantsExperimental Treatment1 Intervention

This arm is optional based on Cohort 1. All participants in Cohort 2 will be receiving VIR-2218 monotherapy.

Group IX: Cohort 1: CPT-B (moderate HI) participants and matched healthy participants will be evaluated firstExperimental Treatment1 Intervention

All participants in Cohort 1 will be receiving VIR-2218 monotherapy.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

VIR-2218

2020

Completed Phase 2

~110

VIR-3434

2020

Completed Phase 1

~120

0 / 2Eligibility 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

RNA interference (RNAi) therapy, such as VIR-2218, works by targeting and degrading specific messenger RNA (mRNA) molecules, thereby preventing the production of proteins that contribute to disease processes. This is particularly useful in liver diseases where the suppression of viral proteins or other pathogenic proteins can halt disease progression. Monoclonal antibody therapy, like VIR-3434, involves the use of lab-engineered antibodies that specifically bind to target antigens, such as viral particles or abnormal cells, marking them for destruction by the immune system. These therapies are significant for liver disease patients as they offer targeted treatment options that can reduce viral load, minimize liver damage, and improve overall liver function with potentially fewer side effects compared to traditional treatments.

Evolution of HCV patient characteristics and DAA regimens in the German Hepatitis C Registry (DHC-R) in 2014 and 2015.