Renal Impairment
Conditions
Brief summary
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
Participants may be enrolled in Cohorts 1 and 2 in a non-randomized way.
Interventions
DRUGVIR-2218
VIR-2218 given by subcutaneous injection
Sponsors
Vir Biotechnology, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
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 40.0 kg/m\^2 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/1.73m\^2 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/1.73m\^2 based on the MDRD equation, or * Severe RI as defined by eGFR level 15-29mL/min/1.73m\^2 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of VIR-2218 and Its Metabolite AS(N-1)3'VIR-2218 | 4 days | Pharmacokinetic samples were collected at -2 hours pre-dose and at 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, and 96 hours post-dose. |
| Area Under The Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of VIR-2218 and Its Metabolite AS(N-1)3'VIR-2218 | 4 days | Pharmacokinetic samples were collected at -2 hours pre-dose and at 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, and 96 hours post-dose. |
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of VIR-2218 and Its Metabolite AS(N-1)3'VIR-2218 | 4 days | Pharmacokinetic samples were collected at -2 hours pre-dose and at 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, and 96 hours post-dose. |
| Fraction Excreted in Urine in Percentage for VIR-2218 | 4 days | — |
| Amount Excreted in Urine for VIR-2218 and Its Metabolite AS(N-1)3'VIR-2218 | 4 days | — |
| Renal Clearance for VIR-2218 and Its Metabolite AS(N-1)3'VIR-2218 | 4 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | 8 weeks |
Countries
United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical Participant Age <=18 years | 0 Participants |
| Age, Categorical Participant Age >=65 years | 9 Participants |
| Age, Categorical Participant Age Between 18 and 65 years | 19 Participants |
| Age, Continuous Cohort 1 Participant Ages | 62.5 years STANDARD_DEVIATION 5.33 |
| Age, Continuous Cohort 2 Participant Ages | 58.5 years STANDARD_DEVIATION 6.53 |
| BMI Cohort 1 BMI | 31.2 kg/m^2 STANDARD_DEVIATION 2.96 |
| BMI Cohort 2 BMI | 32.0 kg/m^2 STANDARD_DEVIATION 3.63 |
| eGFR Cohort 1 eGFR | 108.25 mL/min/1.73 m^2 STANDARD_DEVIATION 17.244 |
| eGFR Cohort 2 eGFR | 100 mL/min/1.73 m^2 STANDARD_DEVIATION 100.507 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Region of Enrollment United States | 8 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 8 Participants |
| Weight Cohort 1 Weight | 86.9 kg STANDARD_DEVIATION 12.38 |
| Weight Cohort 2 Weight | 78.2 kg STANDARD_DEVIATION 6.64 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 2 / 8 | 0 / 8 | 5 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 6 | 0 / 6 |
Outcome results
None listed