COVID-19
Conditions
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.
Interventions
DRUGAT-527
One 550 mg tablet of AT-527 administered every \ 12 hours (twice a day) for a total of 5 days
OTHERPlacebo
One placebo tablet administered every \ 12 hours (twice a day) for a total of 5 days
Sponsors
Atea Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Blinded
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Argentina, Belgium, Brazil, Egypt, Moldova, Romania, South Africa, Spain, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AT-527 - 550 mg BID Part A
AT-527: One 550 mg tablet of AT-527 administered every \
12 hours (twice a day) for a total of 5 days | 41 |
| Placebo for 550 mg BID Part A
Placebo: One placebo tablet administered every \
12 hours (twice a day) for a total of 5 days | 40 |
| AT-527 - 1100 mg BID Part B
AT-527: Two 550 mg tablets of AT-527 administered every \
12 hours (twice a day) for a total of 5 days | 0 |
| Placebo for 1100 mg BID Part B
Placebo: Two placebo tablets administered every \
12 hours (twice a day) for a total of 5 days | 2 |
| Total | 83 |
Baseline characteristics
| Characteristic | AT-527 - 550 mg BID | Placebo for 550 mg BID | Placebo for 1100 mg BID | Total |
|---|---|---|---|---|
| Age, Continuous | 54.3 years STANDARD_DEVIATION 11.07 | 57.4 years STANDARD_DEVIATION 8.33 | 33.5 years STANDARD_DEVIATION 20.5 | 55.8 years STANDARD_DEVIATION 9.88 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 3 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 29 Participants | 32 Participants | 2 Participants | 63 Participants |
| Sex: Female, Male Female | 19 Participants | 25 Participants | 2 Participants | 46 Participants |
| Sex: Female, Male Male | 22 Participants | 15 Participants | 0 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 2 / 40 | 0 / 0 | 1 / 2 |
| other Total, other adverse events | 24 / 40 | 23 / 40 | 0 / 0 | 2 / 2 |
| serious Total, serious adverse events | 5 / 40 | 3 / 40 | 0 / 0 | 1 / 2 |
Outcome results
Primary
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
Time frame: Day 14
Population: Intent-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AT-527 - 550 mg BID | Proportions (Active vs. Placebo) of Subjects With Progressive Respiratory Insufficiency (PRI) on or Before Day 14. | 3 Participants |
| Placebo for 550 mg BID | Proportions (Active vs. Placebo) of Subjects With Progressive Respiratory Insufficiency (PRI) on or Before Day 14. | 4 Participants |
| Placebo for 1100 mg BID | Proportions (Active vs. Placebo) of Subjects With Progressive Respiratory Insufficiency (PRI) on or Before Day 14. | 0 Participants |
p-value: 0.721Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Through Day 14
Population: The modified intent-to-treat (mITT) analysis set included subjects who were randomized and treated and who had a positive SARS-CoV2 test result at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AT-527 - 550 mg BID | Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab | Change from baseline to Day 2 | -0.55 log10 copies/mL | Standard Deviation 1.175 |
| AT-527 - 550 mg BID | Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab | Change from baseline to Day 5 | -1.00 log10 copies/mL | Standard Deviation 1.316 |
| AT-527 - 550 mg BID | Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab | Change from baseline to Day 8 | -1.64 log10 copies/mL | Standard Deviation 1.534 |
| AT-527 - 550 mg BID | Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab | Change from baseline to Day 10 | -1.72 log10 copies/mL | Standard Deviation 1.734 |
| AT-527 - 550 mg BID | Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab | Change from baseline to Day 12 | -2.13 log10 copies/mL | Standard Deviation 2.065 |
| AT-527 - 550 mg BID | Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab | Change from baseline to Day 14 | -2.61 log10 copies/mL | Standard Deviation 1.873 |
| Placebo for 550 mg BID | Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab | Change from baseline to Day 14 | -2.26 log10 copies/mL | Standard Deviation 1.747 |
| Placebo for 550 mg BID | Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab | Change from baseline to Day 2 | -0.02 log10 copies/mL | Standard Deviation 1.838 |
| Placebo for 550 mg BID | Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab | Change from baseline to Day 10 | -2.26 log10 copies/mL | Standard Deviation 1.452 |
| Placebo for 550 mg BID | Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab | Change from baseline to Day 12 | -2.08 log10 copies/mL | Standard Deviation 1.584 |
| Placebo for 550 mg BID | Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab | Change from baseline to Day 5 | -0.80 log10 copies/mL | Standard Deviation 1.853 |
| Placebo for 550 mg BID | Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab | Change from baseline to Day 8 | -1.38 log10 copies/mL | Standard Deviation 1.281 |
| Placebo for 1100 mg BID | Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab | Change from baseline to Day 5 | -2.51 log10 copies/mL | Standard Deviation 0.66 |
| Placebo for 1100 mg BID | Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab | Change from baseline to Day 8 | -3.78 log10 copies/mL | Standard Deviation 1.39 |
| Placebo for 1100 mg BID | Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab | Change from baseline to Day 14 | -4.13 log10 copies/mL | Standard Deviation 1.21 |
| Placebo for 1100 mg BID | Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab | Change from baseline to Day 10 | -4.78 log10 copies/mL | Standard Deviation 2.13 |
| Placebo for 1100 mg BID | Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab | Change from baseline to Day 2 | -1.37 log10 copies/mL | Standard Deviation 1.57 |
| Placebo for 1100 mg BID | Change From Baseline in Amount of SARS-CoV-2 Virus RNA by Nasopharyngeal Swab | Change from baseline to Day 12 | -4.78 log10 copies/mL | Standard Deviation 2.13 |