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

• ClinicalTrials.gov Identifier: NCT05484206
• Recruitment Status: Recruiting
• First Posted: August 2, 2022
• Last Update Posted: May 3, 2024
• Sponsor: Vir Biotechnology, Inc.
• Information provided by (Responsible Party): Vir Biotechnology, Inc.

Tracking Information

• First Submitted Date: July 15, 2022
• First Posted Date: August 2, 2022
• Last Update Posted Date: May 3, 2024
• Actual Study Start Date: September 21, 2022
• Estimated Primary Completion Date: September 25, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 13, 2022)

• Maximum observed Plasma concentration (Cmax) of VIR-2218 and metabolite AS(N-1)3'VIR2218 [ Time Frame: 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 [ Time Frame: 5 days ]
• Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of VIR-2218 metabolite AS(N-1)3'VIR2218 [ Time Frame: 5 days ]
• Maximum observed Plasma concentration (Cmax) of VIR-3434 [ Time Frame: 18 weeks ]
• Area Under The Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast) of VIR-3434 [ Time Frame: 18 weeks ]
• Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of VIR-3434 [ Time Frame: 18 weeks ]

Original Primary Outcome Measures (submitted: July 29, 2022)

• Primary Objective [ Time Frame: 5 days ]
  Maximum observed Plasma concentration (Cmax) of VIR-2218 and metabolite AS(N-1)3'VIR2218
• Primary Outcome [ Time Frame: 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
• Primary Outcome [ Time Frame: 5 days ]
  Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of VIR-2218 metabolite AS(N-1)3'VIR2218

Current Secondary Outcome Measures (submitted: October 13, 2022)

• Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) [ Time Frame: Up to 18 Weeks ]
• Incidence of ADA and titers of ADA to VIR-3434 at each study visit for cohorts receiving VIR-3434 therapy [ Time Frame: 18 Weeks ]

Original Secondary Outcome Measures (submitted: July 29, 2022)

• Secondary Outcome [ Time Frame: 12 Weeks ]
  Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
• Secondary Outcome [ Time Frame: 12 Weeks ]
  Number of participants with clinical laboratory abnormalities

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Hepatic Impairment
• Cirrhosis

Intervention

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

Study Arms

• 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.
  Intervention: Drug: VIR-2218
• 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.
  Intervention: Drug: VIR-2218
• 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.
  Intervention: Drug: VIR-2218
• Experimental: Cohort 4: CPT-A (mild HI) participants and matched healthy participants
  All participants in Cohort 4 will be receiving VIR-3434 monotherapy.
  Intervention: Drug: VIR-3434
• Experimental: Cohort 5: CPT-B (moderate HI) participants and matched healthy participants
  All participants in Cohort 5 will be receiving VIR-3434 monotherapy.
  Intervention: Drug: VIR-3434
• 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.
  Intervention: Drug: VIR-3434
• 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.
  Interventions:

  • Drug: VIR-2218
  • Drug: VIR-3434
• 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.
  Interventions:

  • Drug: VIR-2218
  • Drug: VIR-3434
• 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.
  Interventions:

  • Drug: VIR-2218
  • Drug: VIR-3434

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 13, 2022): 144
• Original Estimated Enrollment (submitted: July 29, 2022): 48
• Estimated Study Completion Date: April 30, 2027
• Estimated Primary Completion Date: September 25, 2026 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05484206
• Other Study ID Numbers: VIR-2218-V107
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Vir Biotechnology, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Vir Biotechnology, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Vir Biotechnology, Inc.
• Verification Date: May 2024