NCT05484206

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
144

participants targeted

Target at P75+ for phase_1

Timeline
12mo left

Started Sep 2022

Longer than P75 for phase_1

Geographic Reach
1 country

5 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress79%
Sep 2022Apr 2027

First Submitted

Initial submission to the registry

July 15, 2022

Completed
18 days until next milestone

First Posted

Study publicly available on registry

August 2, 2022

Completed
2 months until next milestone

Study Start

First participant enrolled

September 21, 2022

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 25, 2026

Expected
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 30, 2027

Last Updated

June 13, 2025

Status Verified

June 1, 2025

Enrollment Period

4 years

First QC Date

July 15, 2022

Last Update Submit

June 10, 2025

Conditions

Hepatic ImpairmentCirrhosis

Keywords

siRNAMonoclonal antibodyHDVCompensated CirrhosisDecompensated Cirrhosis

Outcome Measures

Primary Outcomes (6)

  • Maximum observed Plasma concentration (Cmax) of VIR-2218 and metabolite AS(N-1)3'VIR2218

    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

    5 days

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

    5 days

  • Maximum observed Plasma concentration (Cmax) of VIR-3434

    18 weeks

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

    18 weeks

  • Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of VIR-3434

    18 weeks

Secondary Outcomes (2)

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

    Up to 18 Weeks

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

    18 Weeks

Study Arms (9)

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

EXPERIMENTAL

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

Drug: VIR-2218

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

EXPERIMENTAL

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

Drug: VIR-2218

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

EXPERIMENTAL

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

Drug: VIR-2218

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

EXPERIMENTAL

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

Drug: VIR-3434

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

EXPERIMENTAL

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

Drug: VIR-3434

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

EXPERIMENTAL

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

Drug: VIR-3434

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

EXPERIMENTAL

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

Drug: VIR-2218Drug: VIR-3434

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

EXPERIMENTAL

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

Drug: VIR-2218Drug: VIR-3434

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

EXPERIMENTAL

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

Drug: VIR-2218Drug: VIR-3434

Interventions

VIR-2218DRUG

VIR-2218 given by subcutaneous injection.

Cohort 1: CPT-B (moderate HI) participants and matched healthy participants will be evaluated firstCohort 2: CPT-C (severe HI) participants and matched healthy participantsCohort 3: CPT-A (mild HI) participants and matched healthy participantsCohort 7: CPT-A (mild HI) and matched healthy participantsCohort 8: CPT-B (moderate HI) and matched healthy participantsCohort 9: CPT-C (severe HI) and matched healthy participants
VIR-3434DRUG

VIR-3434 given by subcutaneous injection.

Cohort 4: CPT-A (mild HI) participants and matched healthy participantsCohort 5: CPT-B (moderate HI) participants and matched healthy participantsCohort 6: CPT-C (severe HI) participants and matched healthy participantsCohort 7: CPT-A (mild HI) and matched healthy participantsCohort 8: CPT-B (moderate HI) and matched healthy participantsCohort 9: CPT-C (severe HI) and matched healthy participants

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • Must in the opinion of the Investigator, be in good health based upon medical history, vital signs, physical examination, and screening laboratory evaluations
  • 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

You may not qualify if:

  • 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
  • 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
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Inland Empire Clinical Trials

Rialto, California, 92377, United States

RECRUITING

Orange County Research Center

Tustin, California, 92790, United States

RECRUITING

CenExel Research Centers of America

Hollywood, Florida, 33024, United States

WITHDRAWN

Floridian Clinical Research

Miami Lakes, Florida, 33016, United States

RECRUITING

Texas Liver Institute

San Antonio, Texas, 78215, United States

TERMINATED

MeSH Terms

Conditions

Fibrosis

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and Symptoms

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 15, 2022

First Posted

August 2, 2022

Study Start

September 21, 2022

Primary Completion (Estimated)

September 25, 2026

Study Completion (Estimated)

April 30, 2027

Last Updated

June 13, 2025

Record last verified: 2025-06

Locations

US(5)