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

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

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

Study Overview

• Status: Completed
• Conditions: Renal Impairment; Healthy Volunteer
• Intervention / Treatment: Drug: AT-527; Drug: AT-527; Drug: AT-527 and Probenecid

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada
    • Atea Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A-Mild Renal Impairment; single dose AT-527	Drug: AT-527; single dose AT-527; Other Names: Bemnifosbuvir; Drug: AT-527; Single dose of AT-527 pre- and post-dialysis; Other Names: Bemnifosbuvir
Experimental: Group B-Moderate Renal Impairment; single dose AT-527	Drug: AT-527; single dose AT-527; Other Names: Bemnifosbuvir; Drug: AT-527; Single dose of AT-527 pre- and post-dialysis; Other Names: Bemnifosbuvir
Experimental: Group C-Severe Renal Impairment (optional); single dose AT-527	Drug: AT-527; single dose AT-527; Other Names: Bemnifosbuvir; Drug: AT-527; Single dose of AT-527 pre- and post-dialysis; Other Names: Bemnifosbuvir
Experimental: Group D-End-Stage Renal Disease (optional); single dose of AT-527 pre- and post-dialysis	Drug: AT-527; single dose AT-527; Other Names: Bemnifosbuvir; Drug: AT-527; Single dose of AT-527 pre- and post-dialysis; Other Names: Bemnifosbuvir
Experimental: Group E-Matched Healthy Subjects; Single dose of AT-527 on Days 1 and 15. Probenecid administered twice daily (BID) Days 14-19	Drug: AT-527 and Probenecid; Single dose of AT-527 on Days 1 and 15. Probenecid administered twice daily (BID) Days 14-19; Other Names: Bemnifosbuvir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Atea Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2022
• Primary Completion (Actual): June 15, 2024
• Study Completion (Actual): June 15, 2024

Study Registration Dates

• First Submitted: October 26, 2022
• First Submitted That Met QC Criteria: November 8, 2022
• First Posted (Actual): November 16, 2022

Study Record Updates

• Last Update Posted (Actual): July 31, 2024
• Last Update Submitted That Met QC Criteria: July 29, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency; Antirheumatic Agents; Gout Suppressants; Uricosuric Agents; Probenecid
• Other Study ID Numbers: AT-03A-011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes