Clinical trial NCT05484206: Effect of Hepatic Impairment on the Pharmacokinetics and Safety of VIR-2218 and VIR-3434
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hepatic Impairment
Cirrhosis
Keywords: siRNA
Monoclonal antibody
HDV
Compensated Cirrhosis
Decompensated Cirrhosis
Lead sponsor: Vir Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2022-08-02
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Maximum observed Plasma concentration (Cmax) of VIR-2218 and metabolite AS(N-1)3'VIR2218
timeFrame: 5 days
measure: 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
timeFrame: 5 days
measure: Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of VIR-2218 metabolite AS(N-1)3'VIR2218
timeFrame: 5 days
measure: Maximum observed Plasma concentration (Cmax) of VIR-3434
timeFrame: 18 weeks
measure: Area Under The Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast) of VIR-3434
timeFrame: 18 weeks
measure: Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of VIR-3434
timeFrame: 18 weeks
Secondary outcomes:
measure: Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
timeFrame: Up to 18 Weeks
measure: Incidence of ADA and titers of ADA to VIR-3434 at each study visit for cohorts receiving VIR-3434 therapy
timeFrame: 18 Weeks
Other outcomes:
Locations:
city: Rialto
country: United States
facility: Inland Empire Clinical Trials
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Hollywood
country: United States
facility: CenExel Research Centers of America
state: Florida
city: Miami Lakes
country: United States
facility: Floridian Clinical Research
state: Florida
city: San Antonio
country: United States
facility: Texas Liver Institute
state: Texas
Study officials:
References: