A Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics and Safety of VIR-2218

Study Overview
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Brief Summary
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The rationale of this study is to evaluate the impact of renal function on the PK, safety, and tolerability of VIR-2218 in participants with normal renal function and participants with varying degrees of renal dysfunction who are otherwise medically stable

Detailed Description
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Participants may be enrolled in Cohorts 1 and 2 in a non-randomized way.

Official Title
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A Phase 1, Open-Label, Single-Dose, Parallel-Group Study of the Pharmacokinetics and Safety of VIR-2218 in Adult Participants With Renal Impairment

Conditions
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Renal Impairment

Intervention / Treatment
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* Drug: VIR-2218


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for All Participants: Participants must have stable renal function as defined by less than 20% change in estimated glomerular filtration rate (eGFR) between the first and second screening sample with the first screening visit occurring within 28 days prior to dosing on Day 1 and the second screening visit occurring no more than 14 days apart, but at least 72 hours apart from the first. Body mass index (BMI) within the range 18.5 to 35.0 kg/m2 at screening. Female and Male participants must consent to follow contraception requirements Capability of giving signed informed consent form Inclusion Criteria: Additional Criteria Specific to Healthy Participants: Must be in the opinion of the investigator, be in good health based upon medical history, vital signs, physical examination, and screening laboratory evaluations Must have normal renal function as defined by eGFR ≥ 90 mL/min/1.73m2 based on the Modification of Diet in Renal Disease (MDRD) equation determined from the mean of two measurements of serum creatinine at screening. Inclusion Criteria: Additional Criteria Specific to Participants with Renal Impairment 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 Participants with RI must have chronic moderate or severe RI and be clinically stable per investigator assessment for at least 3 months prior to screening Moderate RI as defined by eGFR level 30-59 mL/min/1.73m2 based on the MDRD equation, or Severe RI as defined by eGFR level 15-29 mL/min/1.73m2 based on the MDRD equation Exclusion Criteria: Criteria for All Participants Any clinically significant medical condition or psychiatric condition that may interfere with study intervention Participants with uncontrolled hypertension, asthma, and/or diabetes (Type I or II). Participants with diabetes Participants with any active malignancy Participants with vasculitis or conditions associated with vasculitis. Participants who have undergone major surgery within 12 months of screening Participants with unstable cardiac functions, abnormality, or clinically significant heart failure Participants with infection of HIV, HAV, HBV, HCV, HDV, or HEV Participants with signs of active infection History of bone marrow or solid organ transplantation Participants with end-stage renal disease or nephrotic syndrome as defined by: participants requiring hemodialysis or peritoneal dialysis, participants who have undergone or are listed for transplant, or participants who have chronic kidney disease with nephrotic syndrome Participants with active nephritis Participants with clinically significant liver disease History of drug or alcohol abuse Unwillingness or inability to follow procedures outlined in protocol Exclusion Criteria: Additional Criteria Specific to Healthy Participants Use of any prescription medications or over-the-counter medications (with the exception of vitamins and/or hormonal contraceptive medications) including herbal products within 30 days prior to D1 of study participation Exclusion Criteria: Additional Criteria Specific to Participants with Renal Impairment Not on stable dose and regimen of any medication(s) (prescription or over-the-counter) that the participants is taking regularly (eg, medications for chronic conditions such as hypertension, high cholesterol, or depression must not be changed in dose or type for at least 2 weeks prior to study drug administration)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: 8 moderate Renal Impairment (RI) participants and 8 matched healthy participants<br> | Drug: VIR-2218<br>* VIR-2218 given by subcutaneous injection<br>|
| Experimental: Cohort 2: 8 severe Renal Impairment (RI) participants and 8 matched healthy participants (optional)<br> | Drug: VIR-2218<br>* VIR-2218 given by subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of VIR-2218 and its metabolite AS(N-1)3'VIR-2218 |  | 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'VIR-2218 |  | 5 days | 
| Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of VIR-2218 metabolite AS(N-1)3'VIR-2218 |  | 5 days | 
| Fraction excreted in urine in percentage for VIR-2218 and its metabolite AS(N-1)3'VIR-2218 |  | 5 days | 
| Amount excreted in urine for VIR-2218 and its metabolite AS(N-1)3'VIR-2218 |  | 5 days | 
| Renal clearance for VIR-2218 and its metabolite AS(N-1)3'VIR-2218 |  | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) |  | 8 weeks |