Safety and Efficacy of AT-527 in Subjects With Moderate Coronavirus Disease (COVID-19) in a Hospital Setting

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of AT-527 in Subjects With Moderate COVID-19

The objectives of this study are to evaluate the safety, tolerability, antiviral activity and efficacy of AT-527 in adult subjects ≥18 years of age with moderate COVID-19 and risk factors for poor outcomes (such as obesity (BMI>30), hypertension, diabetes or asthma). Eligible subjects will be randomized to blinded AT-527 (nucleotide analog) tablets or matching placebo tablets to be administered orally for 5 days. Part A will evaluate an AT-527 dose of 550 mg BID and Part B will evaluate a second dose of AT-527 (1100 mg BID). Local supportive standard of care (SOC) will be allowed for all subjects. Efficacy, antiviral activity and safety observations will be compared for treatment with active AT-527 tablets vs. placebo tablets.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: AT-527; Other: Placebo; Drug: AT-527; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Rosario, Argentina
    • Atea Study Site
  • Vicente Lopez, Argentina
    • Atea Study Site
• Belgium
  • Brussels, Belgium
    • Atea Study Site
  • Mechelen, Belgium
    • Atea Study Site
• Brazil
  • Belo Horizonte, Brazil
    • Atea Study Site
  • Brasília, Brazil
    • Atea Study Site
  • Campo Largo, Brazil
    • Atea Study Site
  • Porto Alegre, Brazil
    • Atea Study Site
  • São Paulo, Brazil
    • Atea Study Site
• Egypt
  • Cairo, Egypt
    • Atea Study Site
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
    • Atea Study Site
• Romania
  • Bucharest, Romania
    • Atea Study Site
• South Africa
  • Bloemfontein, South Africa
    • Atea Study Site
  • Cape Town, South Africa
    • Atea Study Site
  • Centurion, South Africa
    • Atea Study Site
  • George, South Africa
    • Atea Study Site
  • Worcester, South Africa
    • Atea Study Site
• Spain
  • Barcelona, Spain
    • Atea Study Site
  • Madrid, Spain
    • Atea Study Site
  • Pozuelo De Alarcón, Spain
    • Atea Study Site
• Ukraine
  • Brovary, Ukraine
    • Atea Study Site
  • Kyiv, Ukraine
    • Atea Study Site
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Atea Study Site
  • California
    • Davis, California, United States, 95817
      • Atea Study Site
    • Los Angeles, California, United States, 90017
      • Atea Study Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Atea Study Site
  • Florida
    • Orlando, Florida, United States, 32804
      • Atea Study Site
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Atea Study Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Atea Study Site
    • Chicago, Illinois, United States, 60612
      • Atea Study Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Atea Study Site
  • Montana
    • Butte, Montana, United States, 59701
      • Atea Study Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Atea Study Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Atea Study Site
    • Columbus, Ohio, United States, 43203
      • Atea Study Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Atea Study Site
    • Columbia, South Carolina, United States, 29203
      • Atea Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Hospitalized or in a hospital-affiliated confinement facility
• SARS-CoV-2 positive
• Initial COVID-19 symptom onset within 5 days prior to Screening
• SpO2 ≥ 93% on room air or requires ≤ 2L/min oxygen by nasal cannula or mask to maintain SpO2 ≥ 93%
• Must also have a history of at least one of the following known risk factors for poor outcomes: obesity (BMI>30), hypertension, diabetes or asthma.

Key Exclusion Criteria:

• Severe or critical COVID-19 illness: RR ≥30, HR ≥125, SpO2 <93% on room air or requires >2L/min oxygen by nasal cannula or mask to maintain SpO2 ≥93%, systolic blood pressure < 90 mm Hg, diastolic blood pressure < 60 mm Hg or PaO2/FiO2 <300
• Requires mechanical ventilation
• Lobar or segmental consolidation on chest imaging.
• Treatment with other drugs thought to possibly have activity against SARS-CoV-2
• ALT or AST > 5 x upper limit of normal (ULN)
• Female subject is pregnant or breastfeeding
• Has received or is expected to receive any dose of a SARS-CoV-2 vaccine before the Day 14 visit (Part B).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: AT-527 - 550 mg BID; Part A	Drug: AT-527; One 550 mg tablet of AT-527 administered every ~12 hours (twice a day) for a total of 5 days; Drug: AT-527; Two 550 mg tablets of AT-527 administered every ~12 hours (twice a day) for a total of 5 days
Placebo Comparator: Placebo for 550 mg BID; Part A	Other: Placebo; One placebo tablet administered every ~12 hours (twice a day) for a total of 5 days; Other: Placebo; Two placebo tablets administered every ~12 hours (twice a day) for a total of 5 days
Active Comparator: AT-527 - 1100 mg BID; Part B	Drug: AT-527; One 550 mg tablet of AT-527 administered every ~12 hours (twice a day) for a total of 5 days; Drug: AT-527; Two 550 mg tablets of AT-527 administered every ~12 hours (twice a day) for a total of 5 days
Placebo Comparator: Placebo for 1100 mg BID; Part B	Other: Placebo; One placebo tablet administered every ~12 hours (twice a day) for a total of 5 days; Other: Placebo; Two placebo tablets administered every ~12 hours (twice a day) for a total of 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportions (Active vs. Placebo) of Subjects With Progressive Respiratory Insufficiency (PRI) on or Before Day 14.	Progressive respiratory insufficiency defined as a ≥ 2-tier increase in respiratory support methods required to maintain satisfactory oxygenation (SpO2 ≥ 93%), using the 6-tier hierarchical scale of respiratory support methods, within the 14-day study period. Level 1:Normal oxygenation on room air (SpO2 ≥93), no need for supplemental O2 Level 2:Persistent hypoxemia on room air (SpO2 <93) with requirement for low-level supplemental O2 by nasal cannula/mask (up to 2L/min) to maintain SpO2 ≥93 Level 3:Requirement for higher levels of passive supplemental O2 by nasal cannula or mask (≥2 L/min) to maintain SpO2 ≥93 Level 4:Requirement for oxygenation by positive-pressure devices Level 5:Required invasive respiratory support (intubated mechanical ventilation or ECMO) Level 6:Death	Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab	Change in the viral load as measured by swab of the upper part of the pharynx.	Through Day 14

Collaborators and Investigators

• Sponsor: Atea Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2020
• Primary Completion (Actual): January 10, 2022
• Study Completion (Actual): February 28, 2022

Study Registration Dates

• First Submitted: May 16, 2020
• First Submitted That Met QC Criteria: May 19, 2020
• First Posted (Actual): May 20, 2020

Study Record Updates

• Last Update Posted (Estimate): March 9, 2023
• Last Update Submitted That Met QC Criteria: February 8, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: AT-03A-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No