Effect of Hepatic Impairment on the Pharmacokinetics and Safety of VIR-2218 and VIR-3434

A Phase 1 Open-Label, Single-Dose, Parallel-Group Study of the Pharmacokinetics and Safety of VIR-2218 and VIR-3434 Monotherapy and Combination Therapy in Adult Participants With Hepatic Impairment

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.

Study Overview

• Status: Recruiting
• Conditions: Cirrhosis; Hepatic Impairment
• Intervention / Treatment: Drug: VIR-2218; Drug: VIR-3434

Detailed Description

Participants may be enrolled in Cohorts 1, 2, 3, 4, 5, 6, 7, 8, and 9 in a non-randomized way.

• Study Type: Interventional
• Enrollment (Estimated): 144
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Rialto, California, United States, 92377
      • Recruiting
      • Inland Empire Clinical Trials
      • Contact: Amanda Benavides; Phone Number: 909-883-2999; Email: abenavides@ieliverfoundation.com
    • Tustin, California, United States, 92790
      • Recruiting
      • Orange County Research Center
      • Contact: Melanie Goerlitz; Phone Number: 714-550-9990; Email: Melanie.goerlitz@ocresearchcenter.com
  • Florida
    • Hollywood, Florida, United States, 33024
      • Withdrawn
      • CenExel Research Centers of America
    • Miami Lakes, Florida, United States, 33016
      • Recruiting
      • Floridian Clinical Research
      • Contact: Julio Lopez; Phone Number: 124 305-330-9977; Email: jlopez@floridiancr.com
  • Texas
    • San Antonio, Texas, United States, 78215
      • Terminated
      • Texas Liver Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: VIR-2218; VIR-2218 given by subcutaneous injection.
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.	Drug: VIR-2218; VIR-2218 given by subcutaneous injection.
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.	Drug: VIR-2218; VIR-2218 given by subcutaneous injection.
Experimental: Cohort 4: CPT-A (mild HI) participants and matched healthy participants; All participants in Cohort 4 will be receiving VIR-3434 monotherapy.	Drug: VIR-3434; VIR-3434 given by subcutaneous injection.
Experimental: Cohort 5: CPT-B (moderate HI) participants and matched healthy participants; All participants in Cohort 5 will be receiving VIR-3434 monotherapy.	Drug: VIR-3434; VIR-3434 given by subcutaneous injection.
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.	Drug: VIR-3434; VIR-3434 given by subcutaneous injection.
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.	Drug: VIR-2218; VIR-2218 given by subcutaneous injection.; Drug: VIR-3434; VIR-3434 given by subcutaneous injection.
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.	Drug: VIR-2218; VIR-2218 given by subcutaneous injection.; Drug: VIR-3434; VIR-3434 given by subcutaneous injection.
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.	Drug: VIR-2218; VIR-2218 given by subcutaneous injection.; Drug: VIR-3434; VIR-3434 given by subcutaneous injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Vir Biotechnology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2022
• Primary Completion (Estimated): September 25, 2026
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: July 15, 2022
• First Submitted That Met QC Criteria: July 29, 2022
• First Posted (Actual): August 2, 2022

Study Record Updates

• Last Update Posted (Actual): May 3, 2024
• Last Update Submitted That Met QC Criteria: May 1, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Monoclonal antibody; Compensated Cirrhosis; HDV; siRNA; Decompensated Cirrhosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: VIR-2218-V107

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No