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

Cirrhosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05484206
• Other study ID #: VIR-2218-V107
• Status: Recruiting
• Phase: Phase 1
• Start date: September 21, 2022
• Est. completion date: March 2024

Study information

• Verified date: April 2023
• Source: Vir Biotechnology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 144
• Est. completion date: March 2024
• Est. primary completion date: September 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Cirrhosis
• Fibrosis
• Hepatic Impairment
• Liver Cirrhosis
• Liver Diseases

Intervention

Drug:
• VIR-2218
VIR-2218 given by subcutaneous injection.
• VIR-3434
VIR-3434 given by subcutaneous injection.

Locations

Country	Name	City	State
United States	CenExel Research Centers of America	Hollywood	Florida
United States	Floridian Clinical Research	Miami Lakes	Florida
United States	Inland Empire Clinical Trials	Rialto	California
United States	Texas Liver Institute	San Antonio	Texas
United States	Orange County Research Center	Tustin	California

Sponsors (1)

Lead Sponsor	Collaborator
Vir Biotechnology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum observed Plasma concentration (Cmax) of VIR-2218 and metabolite AS(N-1)3'VIR2218		5 days
Primary	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
Primary	Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of VIR-2218 metabolite AS(N-1)3'VIR2218		5 days
Primary	Maximum observed Plasma concentration (Cmax) of VIR-3434		18 weeks
Primary	Area Under The Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast) of VIR-3434		18 weeks
Primary	Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of VIR-3434		18 weeks
Secondary	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)		Up to 18 Weeks
Secondary	Incidence of ADA and titers of ADA to VIR-3434 at each study visit for cohorts receiving VIR-3434 therapy		18 Weeks