Recruiting
Phase 1

VIR-2218 & VIR-3434

Sponsor:

Vir Biotechnology, Inc.

Code:

NCT05484206

Conditions

Hepatic Impairment

Cirrhosis

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Accepted

Interventions

VIR-2218

VIR-3434

Study Details

Brief summary:

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 to assess the pharmacokinetic (PK) exposure, safety, and tolerability of VIR-2218 and VIR-3434 in participants with cirrhosis and Hepatic Impairment, defined using the Child-Pugh-Turcotte (CPT) categorization.

Conditions

Hepatic Impairment

Cirrhosis

Study ID

NCT05484206

Start date

Sep 21, 2022

Status verified date

Jun, 2025

Completion date

Apr 30, 2027

Anticipated

Primary completion date

Sep 25, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Accepted

Inclusion Criteria:

  • Must be ≥18 to ≤70 years of age at screening
  • Must have a calculated BMI from 18.5 ≤ BMI ≤ 40 kg/m2
  • All participants must have an eGFR ≥ 60 mL/min as calculated by the Modification of Diet in Renal Disease (MDRD) equation

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

Inclusion criteria: Hepatic impaired participants

  • Apart from hepatic insufficiency, participants must, in the opinion of the Investigator be sufficiently healthy for study participation based on medical history, physical examination, vital signs, and screening laboratory evaluations
  • Participant is considered to have chronic, stable moderate, severe, mild HI (of any etiology excluding chronic HBV and HDV) and has been clinically stable per Investigator assessment for at least 1 month prior to screening
  • CPT score of 5 to 6 for mild HI at screening
  • CPT score 7-9 for moderate HI at screening
  • CPT score 10-15 severe HI at screening

Exclusion Criteria:

  • Participants with unstable cardiac function or evidence of previous myocardial infarction in the past 12 months or any clinically significant active cardiovascular disease that, in the opinion of the Investigator, could interfere with the safety of the participant
  • Any clinically significant conduction abnormality or arrhythmia (including non-sustained or sustained ventricular tachycardia as per Investigator's assessment)
  • Infection with human immunodeficiency virus (HIV), hepatitis A virus (HAV), HBV (positive HBsAg or positive hepatitis B core antibody with negative hepatitis B surface antibody), hepatitis C virus (HCV), HDV or hepatitis E virus (HEV). HCV antibody positive participants with a negative HCV RNA are eligible. HDV antibody positive participants with a negative HDV RNA are eligible

Exclusion criteria: Healthy matched participants

  • Systolic BP is outside the range of 90-160 mmHg, or diastolic BP is outside the range of 45-95 mmHg or heart rate is outside the range of 50-100 beats per minute (bpm) for female participants or 45-100 bpm for male participants at screening
  • Use of any prescription medications or over-the-counter medications (with the exception of vitamins and/or hormonal contraceptive medication) within 30 days prior to D1 of study participation

Exclusion criteria: Participants with Hepatic impairment

  • Not on stable dose and regimen of any medication
  • Acute or worsening chronic hepatitis
  • Participants requiring paracentesis more than once a month
  • Participants with refractory encephalopathy or significant Central Nervous System
  • History of gastric or esophageal variceal bleeding within the past 6 months
  • Participants with Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement
  • Presence of hepatopulmonary or hepatorenal syndrome
  • Presence of primarily cholestatic liver diseases
  • History of or currently listed for liver transplantation

Study Design

Enrollment

144 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Cohort 1: CPT-B (moderate HI) participants and matched healthy participants will be evaluated first

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

experimental: Cohort 2: CPT-C (severe HI) participants and matched healthy participants

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

experimental: Cohort 3: CPT-A (mild HI) participants and matched healthy participants

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

experimental: Cohort 4: CPT-A (mild HI) participants and matched healthy participants

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

experimental: Cohort 5: CPT-B (moderate HI) participants and matched healthy participants

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

experimental: Cohort 6: CPT-C (severe HI) participants and matched healthy participants

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

experimental: Cohort 7: CPT-A (mild HI) and matched healthy participants

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

experimental: Cohort 8: CPT-B (moderate HI) and matched healthy participants

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

experimental: Cohort 9: CPT-C (severe HI) and matched healthy participants

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

Interventions

VIR-2218

VIR-2218 given by subcutaneous injection.

VIR-3434

VIR-3434 given by subcutaneous injection.

Primary outcome measure

  • Maximum observed Plasma concentration (Cmax) of VIR-2218 and metabolite AS(N-1)3'VIR2218 [ Time Frame: 5 days ]
  • 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 [ Time Frame: 5 days ]
  • Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of VIR-2218 metabolite AS(N-1)3'VIR2218 [ Time Frame: 5 days ]
  • Maximum observed Plasma concentration (Cmax) of VIR-3434 [ Time Frame: 18 weeks ]
  • Area Under The Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast) of VIR-3434 [ Time Frame: 18 weeks ]
  • Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of VIR-3434 [ Time Frame: 18 weeks ]

Central Contacts and Locations

Locations

Inland Empire Clinical Trials

Recruiting

Rialto, California, United States, 92377

Contacts

Amanda Benavides

909-883-2999abenavides@ieliverfoundation.com

Orange County Research Center

Recruiting

Tustin, California, United States, 92790

Contacts

Melanie Goerlitz

714-550-9990Melanie.goerlitz@ocresearchcenter.com

Floridian Clinical Research

Recruiting

Miami Lakes, Florida, United States, 33016

Contacts

Julio Lopez

305-330-9977jlopez@floridiancr.com

More Information

Sponsor

Vir Biotechnology, Inc.

Last update posted

Jun 13, 2025

Last verified

Jun, 2025

Keywords

  • siRNA
  • Monoclonal antibody
  • HDV
  • Compensated Cirrhosis
  • Decompensated Cirrhosis

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Vir Biotechnology, Inc. on 2025-06-13.