144 Participants Needed

VIR-2218 + VIR-3434 for Liver Cirrhosis

Recruiting at 3 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Vir Biotechnology, Inc.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, VIR-2218 and VIR-3434, to evaluate their effects both individually and combined in people with liver cirrhosis. The goal is to understand how the body absorbs these treatments and to assess their safety and tolerability. The trial seeks participants with stable liver issues for at least a month, excluding those with hepatitis B or D. Participants will be grouped by the severity of their liver condition to receive different treatment combinations. This trial suits individuals with chronic liver problems who are otherwise in stable health. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive these new treatments.

Will I have to stop taking my current medications?

If you are a healthy participant, you must stop taking any prescription or over-the-counter medications (except vitamins and hormonal contraceptives) 30 days before the study. If you have liver impairment, you need to be on a stable dose and regimen of your current medications.

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

Research has shown that VIR-2218 is generally well-tolerated. In one study, individuals with chronic hepatitis B did not experience serious heart problems after a single dose. Any side effects were related to their liver condition, not to VIR-2218.

For VIR-3434, early results suggest it is safe and helps reduce certain viruses in the liver. Studies have found no major safety issues.

The combination of VIR-2218 and VIR-3434 is also under investigation. Early data from these studies show promising safety results, with only mild increases in liver enzymes in some cases, a common and manageable side effect.

Overall, these treatments appear well-tolerated, but further research is needed to fully confirm their safety.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about VIR-2218 and VIR-3434 because they offer a new approach to treating liver cirrhosis. Unlike traditional treatments that mainly focus on managing symptoms and slowing disease progression, these drugs aim to directly target the underlying causes of liver damage. VIR-2218 is a small interfering RNA (siRNA) therapy that reduces the production of harmful proteins by silencing specific viral genes, while VIR-3434 is an antibody that neutralizes viruses and clears them from the body. This combination could potentially provide a more effective way to combat liver cirrhosis by addressing the root of the disease rather than just its symptoms.

What evidence suggests that this trial's treatments could be effective for liver cirrhosis?

Studies have shown promising results for VIR-2218 and VIR-3434 in treating liver conditions. VIR-2218, administered to participants in some trial arms, has significantly lowered hepatitis B surface antigen (HBsAg) levels, indicating infection in chronic hepatitis B. VIR-3434, another treatment option in this trial, is a potent antibody that has also reduced HBsAg levels in studies with special mice that mimic human liver conditions. In certain trial arms, participants receive a combination of VIR-2218 and VIR-3434, which has led to a noticeable drop in HBsAg levels, specifically by 2.7-3.1 log10 IU/mL. This combination has also shown positive results, with some participants losing HBsAg, an important step toward controlling the virus. Overall, these findings suggest that both treatments could benefit liver conditions.26789

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Healthy matched participants must, in the opinion of the Investigator, be in good health based upon medical history, vital signs, physical examination, and screening laboratory evaluations
My liver is not working well, but I am healthy enough for the study according to my doctor.
CPT score of 5 to 6 for mild HI at screening
See 5 more

Exclusion Criteria

I am currently listed for or have had a liver transplant.
Any clinically significant conduction abnormality or arrhythmia (including non-sustained or sustained ventricular tachycardia as per Investigator's assessment)
I have HIV, hepatitis A, B, C, D, or E but my viral load is undetectable if positive for HCV or HDV.
See 11 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of VIR-2218 up to 200 mg SC or VIR-3434 at 300 mg SC monotherapy or a combination of VIR-2218 and VIR-3434

1 day

Follow-up

Participants are monitored for safety and pharmacokinetic exposure after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • VIR-2218
  • VIR-3434
Trial Overview 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.
How Is the Trial Designed?
9Treatment groups
Experimental Treatment
Group I: Cohort 9: CPT-C (severe HI) and matched healthy participantsExperimental Treatment2 Interventions
Group II: Cohort 8: CPT-B (moderate HI) and matched healthy participantsExperimental Treatment2 Interventions
Group III: Cohort 7: CPT-A (mild HI) and matched healthy participantsExperimental Treatment2 Interventions
Group IV: Cohort 6: CPT-C (severe HI) participants and matched healthy participantsExperimental Treatment1 Intervention
Group V: Cohort 5: CPT-B (moderate HI) participants and matched healthy participantsExperimental Treatment1 Intervention
Group VI: Cohort 4: CPT-A (mild HI) participants and matched healthy participantsExperimental Treatment1 Intervention
Group VII: Cohort 3: CPT-A (mild HI) participants and matched healthy participantsExperimental Treatment1 Intervention
Group VIII: Cohort 2: CPT-C (severe HI) participants and matched healthy participantsExperimental Treatment1 Intervention
Group IX: Cohort 1: CPT-B (moderate HI) participants and matched healthy participants will be evaluated firstExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Vir Biotechnology, Inc.

Lead Sponsor

Trials
30
Recruited
13,300+

Citations

Effect of Hepatic Impairment on the Pharmacokinetics and ...In this study, a single dose of VIR-2218 up to 200 mg SC or VIR-3434 at 300 mg SC monotherapy or a combination of VIR-2218 and VIR-3434 will be administered ...
News DetailsAs 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.
A comprehensive review of phases II and III therapeutic ...Both VIR-2218 and VIR-3434 were well-tolerated with mild adverse effects. The study was instrumental in showing that the combination of VIR-2218 and VIR-3434 ...
Vir Biotechnology Announces Positive End-of-Treatment ...The doublet regimen resulted in 50% (4/8) of participants who had achieved HBsAg loss also achieving anti-HBs seroconversion. All participants ...
Vir Biotechnology Corporate PresentationData demonstrate the ability of VIR-2218 + VIR-3434, without PEG-IFN-α, to achieve HBsAg loss at EOT. Treatment with VIR-3434 monotherapy and ...
6.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/39389081/
VIR-2218 (elebsiran) plus pegylated interferon-alfa-2a in ...We aimed to evaluate the safety and antiviral activity of VIR-2218 with ... Adults (aged 18-65 years) with chronic HBV infection without cirrhosis ...
Evaluation of RNAi therapeutics VIR-2218 and ALN-HBV ...If left untreated, cHBV infection can result in active chronic liver disease and often progresses to cirrhosis, liver failure, hepatocellular ...
Pharmacokinetics and Safety of VIR-2218 Monotherapy in ...They were consistent with underlying cirrhosis and were considered unrelated to VIR-2218. There were no clinical cardiovascular events. Conclusion: A single ...
Clinical and Preclinical Single-Dose Pharmacokinetics of VIR ...... cirrhosis, liver failure, and hepatocellular carcinoma [1]. An ... The safety data for VIR-2218 will be described in a separate ...
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