Study of AT-527 in Subjects With Normal and Impaired Renal Function

Study Overview
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Brief Summary
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Study of AT-527 in Subjects with Normal and Impaired Renal Function

Official Title
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A Phase 1, Open-Label, Parallel-Group, Single-Dose Adaptive Study to Evaluate the Safety and Pharmacokinetics of AT-527 in Adult Subjects With Normal and Impaired Renal Function Sub-Study: Effects of Probenecid on the Pharmacokinetics of AT-527 in Healthy Adult Subjects

Conditions
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Healthy Volunteer, Renal Impairment

Intervention / Treatment
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* Drug: AT-527
* Drug: AT-527
* Drug: AT-527 and Probenecid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must agree to use two methods of birth control from Screening through 90 days after administration of the last dose of study drug Females must have a negative pregnancy test at Screening and prior to dosing BMI of 18.5 to 42.0 kg/m2 Willing to comply with the study requirements and to provide written informed consent Subjects with Normal Renal Function (Group E): Medically healthy, in the opinion of an Investigator Normal renal function with eGFR ≥ 90 mL/min/1.73m2 at Screening Renal Impaired Subjects (Groups A, B, and C): Considered stable in the judgement of an Investigator Presence of severe renal impairment (eGFR ≥ 15 and < 30 mL/min/1.73m2), moderate renal impairment (eGFR ≥ 30 and < 60 mL/min/1.73m2) or mild renal impairment (eGFR ≥ 60 and < 90 mL/min/1.73m2) at Screening: renal impairment should have been stable for at least 1 month prior to Screening. Subjects with End-Stage Renal Disease -ESRD (Group D) Considered clinically stable in the opinion of the Investigator Presence of ESRD (eGFR <15 mL/min/1.73m2 and being on intermittent hemodialysis) at Screening and have been stable for at least 1 month prior to Screening Exclusion Criteria: Pregnant or breastfeeding Infected with HIV or COVID-19 Abuse of alcohol or drugs Use of other investigational drugs within 28 days of dosing Other clinically significant medical conditions or laboratory abnormalities Subjects with Normal Renal Function (Group E): • Any clinically significant illness in the opinion of the investigator Subjects with Impaired Renal Function (Group A, B, C and D): History of renal transplant Presence of poorly controlled Type 1 or Type 2 diabetes as defined by Hemoglobin A1c (HbA1c) > 10% Subjects requiring treatment for renal impairment or other chronic disease must be on a stable treatment plan

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Group A-Mild Renal Impairment<br>single dose AT-527 | Drug: AT-527<br>* single dose AT-527<br>* Other names: Bemnifosbuvir;|
| Experimental: Group B-Moderate Renal Impairment<br>single dose AT-527 | Drug: AT-527<br>* single dose AT-527<br>* Other names: Bemnifosbuvir;|
| Experimental: Group C-Severe Renal Impairment (optional)<br>single dose AT-527 | Drug: AT-527<br>* single dose AT-527<br>* Other names: Bemnifosbuvir;|
| Experimental: Group D-End-Stage Renal Disease (optional)<br>single dose of AT-527 pre- and post-dialysis | Drug: AT-527<br>* Single dose of AT-527 pre- and post-dialysis<br>* Other names: Bemnifosbuvir;|
| Experimental: Group E-Matched Healthy Subjects<br>Single dose of AT-527 on Days 1 and 15. Probenecid administered twice daily (BID) Days 14-19 | Drug: AT-527 and Probenecid<br>* Single dose of AT-527 on Days 1 and 15. Probenecid administered twice daily (BID) Days 14-19<br>* Other names: Bemnifosbuvir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of AT-527 Maximum plasma concentration (Cmax) |  | Day 1 | 
| Pharmacokinetics (PK) of AT-527 Area under the plasma concentration-time curve (AUC) |  | Day 1 | 
| Pharmacokinetics (PK) of AT-527 AUC |  | Day 1 |