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

Study Overview
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Brief Summary
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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.

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

Conditions
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COVID-19

Intervention / Treatment
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* Drug: AT-527
* Other: Placebo
* Drug: AT-527
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 |