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

Phase 2

Terminated

Brief Summary: 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.

Recruitment & Eligibility

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).

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Proportions (Active vs. Placebo) of Subjects With Progressive Respiratory Insufficiency (PRI) on or Before Day 14.	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

Secondary Outcome Measures

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