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

Vir Biotechnology

Status and phase: Enrolling; Phase 1

Conditions: Hepatic Impairment; Cirrhosis

Treatments: Drug: VIR-2218; Drug: VIR-3434

Study type: Interventional

Funder types: Industry

Identifiers

NCT05484206

VIR-2218-V107

Details and patient eligibility

About

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.

Full description

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

Enrollment: 144 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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144 participants in 9 patient groups

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

Experimental group

Description:

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

Treatment:

Drug: VIR-2218

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

Experimental group

Description:

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

Treatment:

Drug: VIR-2218

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

Experimental group

Description:

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

Treatment:

Drug: VIR-2218

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

Experimental group

Description:

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

Treatment:

Drug: VIR-3434

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

Experimental group

Description:

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

Treatment:

Drug: VIR-3434

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

Experimental group

Description:

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

Treatment:

Drug: VIR-3434

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

Experimental group

Description:

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

Treatment:

Drug: VIR-3434

Drug: VIR-2218

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

Experimental group

Description:

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

Treatment:

Drug: VIR-3434

Drug: VIR-2218

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

Experimental group

Description:

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

Treatment:

Drug: VIR-3434

Drug: VIR-2218