COVID-19
Conditions
Brief summary
This randomized study evaluates the antiviral activity, safety, efficacy and pharmacokinetics of AT-527 versus a placebo in participants with mild or moderate coronavirus disease (COVID-19) who are not hospitalized.
Interventions
DRUGAT-527
Results from Arm AT-527 500 mg determined the dose and regimen to be used for AT-527 1100 mg.
DRUGPlacebo
The dose and regimen of the placebo will match that of the respective AT-527 comparator arm.
Sponsors
Atea Pharmaceuticals, Inc.
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Positive SARS-CoV-2 diagnostic test (RT-PCR or rapid antigen test)at screening * Has symptoms consistent with mild or moderate COVID-19, as determined by the investigator, with onset ≤5 days prior to randomization
Exclusion criteria
* Clinical signs indicative of COVID-19 illness requiring hospitalization, defined as any of the following: shortness of breath at rest, respiratory rate ≥30, heart rate ≥125, peripheral capillary oxygen saturation ≤93% on room air * Treatment with a therapeutic agent against SARS-CoV-2 including, but not limited to, other direct acting antivirals, convalescent plasma, monoclonal antibodies against SARS CoV-2, or intravenous immunoglobulin within 3 months or less than 5 drug elimination half-lives (whichever is longer) prior to screening * Requirement, in the opinion of the investigator, for any of the prohibited medications during the study * Use of hydroxychloroquine or amiodarone within 3 months of screening * Pregnant or breastfeeding, or intending to become pregnant during the study or within 30 days after the final dose of AT-527. Women of childbearing potential must have a negative urine pregnancy test result at screening * Abnormal laboratory test results at screening * Clinically significant abnormal ECG, as determined by the Investigator, at screening * Planned procedure or surgery during the study * Known allergy or hypersensitivity to study drug or drug product excipients * Substance abuse, as determined by the investigator, within 12 months prior to screening * Poor peripheral venous access * Malabsorption syndrome or other condition that would interfere with enteral absorption * Any clinically significant history of epistaxis within the last 3 months and/or history of being hospitalized due to epistaxis of any previous occasion * History of anaphylaxis * Any uncontrolled serious medical condition or other clinically significant abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 550 mg and Matched Placebo | Baseline, Day 3, Day 5, Day 7 | SARS-CoV-2 virus RNA was measured by reverse-transcription polymerase chain reaction (RT-PCR) from nasopharyngeal (NP) swabs. The change from baseline was estimated from an ANCOVA model with baseline viral load as a covariate. Reported here is the adjusted mean change from baseline. A negative change from baseline indicates an improvement. |
| Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 1100 mg and Pooled Placebo | Baseline, Day 3, Day 5, Day 7 | SARS-CoV-2 virus RNA was measured by reverse-transcription polymerase chain reaction (RT-PCR) from NP swabs. The change from baseline was estimated from an ANCOVA model with baseline viral load as a covariate. Reported here is the adjusted mean change from baseline. A negative change from baseline indicates an improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Baseline, Day 3, Day 5, Day 7 | Reported here is the percentage of participants with a positive virus RNA by RT-PCR test result above or equal to the limit of quantification (LOQ). RT-PCR was measured from NP swabs. |
| Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA | Baseline, Day 3, Day 5, Day 7 | AUC is the amount of SARS-CoV-2 virus RNA from baseline to the last sample timepoint and was calculated using the trapezoidal method. RT-PCR was measured from NP swabs. |
| Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours) | Up to 28 Days | COVID-19 symptoms were evaluated using the first 12 items in the COVID-19 Symptom Diary, which included the following 12 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, and diarrhea. The symptoms were scored on the 4-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe).Time to alleviation or improvement is defined as the length of time taken from start of treatment to the point at which all of the following three criteria are met and maintained for a concurrent duration of at least 21.5 hours: new symptoms with a score of 0 or 1; pre- existing and worsened due to COVID-19 symptoms with at least a single category improvement from baseline; pre-existing and not worsened due to COVID-19 symptoms remaining the same or at least a single category improvement from baseline. |
| Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours) | Up to 28 Days | COVID-19 symptoms were evaluated using the first 12 items in the COVID-19 Symptom Diary, which included the following 12 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, and diarrhea. The symptoms were scored on the 4-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe). Time to alleviation or improvement is defined as the length of time taken from start of treatment to the point at which all of the following three criteria are met and maintained for a concurrent duration of at least 43 hours: new symptoms with a score of 0 or 1; pre- existing and worsened due to COVID-19 symptoms with at least a single category improvement from baseline; pre-existing and not worsened due to COVID-19 symptoms remaining the same or at least a single category improvement from baseline. |
| Time to Alleviation of COVID-19 Symptoms (21.5 Hours) | Up to 28 Days | COVID-19 symptoms were evaluated using the first 12 items in the COVID-19 Symptom Diary, which included the following 12 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, and diarrhea. The symptoms were scored on the 4-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe). Time to alleviation of COVID-19 symptoms is defined as the length of time taken from start of treatment to the point at which the following criterion is met and maintained for at least 21.5 hours: Score of 0 or 1 on Items 1-12 of the COVID-19 Symptom Diary, regardless of if the symptom is pre-existing or new. |
| Time to Alleviation of COVID-19 Symptoms (43 Hours) | Up to 28 Days | COVID-19 symptoms were evaluated using the first 12 items in the COVID-19 Symptom Diary, which included the following 12 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, and diarrhea. The symptoms were scored on the 4-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe). Time to alleviation of COVID-19 symptoms is defined as the length of time taken from start of treatment to the point at which the following criterion is met and maintained for at least 43 hours: Score of 0 or 1 on Items 1-12 of the COVID-19 Symptom Diary, regardless of if the symptom is pre-existing or new. |
| Time to Cessation of SARS-CoV-2 Viral Shedding | Up to Day 7 | Time to cessation of viral shedding was defined as the time between the initiation of any study treatment and the first time when a negative or below the limit of detection RT-PCR test result was obtained. RT-PCR was measured from NP swabs. Median, 25th and 75th percentiles were estimated from the Kaplan-Meier curve. |
| Percentage of Participants With COVID-19 Related Complications | Up to 33 Days | COVID-19 related complications include death, hospitalization, radiologically confirmed pneumonia, acute respiratory failure, sepsis, coagulopathy, pericarditis, myocarditis, and cardiac failure. |
| Time to Alleviation of an Individual Symptom | Up to 28 Days | The COVID-19 Symptom Diary included the following 14 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, diarrhea, sense of smell over the past 7 days and sense of taste over the past 7 days. The severity of items 1-12 was recorded on a 4-point Likert scale (none=0, mild=1, moderate=2, severe=3). Items 13-14 were recorded on a 3-point Likert scale (same as usual=0, less than usual=1, no sense=2). Time to alleviation of an individual symptom was defined as the time taken from the start of treatment to the point at which the following criterion was met and maintained (for each individual symptom) for at least 21.5 hours: score of 0 or 1 for Items 1-12 of the COVID-19 Symptom Diary; score of 0 for Items 13 and 14 of the COVID-19 Symptom Diary. |
| Percentage of Participants With Adverse Events (AEs) | Up to 33 Days | An AE is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any of the following: any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the medicinal product, any new disease or exacerbation of an existing disease, recurrence of an intermittent medical condition not present at baseline or related to a protocol-mandated intervention. |
| Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | Day 1: pre-dose, 1 hour, 3 hours; Day 3: pre-dose; Day 5: pre-dose, 3 hours, 48 hours | AT-511 is the free base form of AT-527. Its major metabolites are AT-551, AT-229, and AT-273. |
| Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | Day 1: pre-dose, 1 hour, 4 hours; Day 3: pre-dose; Day 5: pre-dose, 1 hour, 4 hours, 48 hours | AT-511 is the free base form of AT-527. Its major metabolites are AT-551, AT-229, and AT-273. |
| Duration of Fever | Up to 28 Days | Duration of fever was defined as the time from start of treatment to return to an afebrile state (temperature ≤ 37.5°C) maintained for at least 21.5 hours. |
| Time to Sustained Non-Detectable SARS-CoV-2 Virus RNA | Up to Day 7 | Time to sustained non-detectable SARS-CoV-2 virus RNA was defined as the time between the initiation of any study treatment and first time when a negative or below the limit of detection test result by RT-PCR is obtained after which no positive test above or equal to the limit of detection was reported. RT-PCR was measured from NP swabs. Median, 25th and 75th percentiles were estimated from the Kaplan-Meier curve. |
Countries
Canada, Greece, Ireland, Latvia, Spain, United Kingdom
Participant flow
Recruitment details
Participants were enrolled in the study at sites in the United Kingdom, Spain, Greece, Latvia, Ireland and Canada.
Pre-assignment details
The study enrolled non-hospitalized adult participants with mild or moderate COVID-19. Four enrolled participants were not treated and are not included in the Results.
Participants by arm
| Arm | Count |
|---|---|
| Pooled Placebo Participants received placebo matched to 550 mg or 1100 mg AT-527 twice a day (BID) on Days 1-5. | 40 |
| AT-527 550 mg (1x550 mg) Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5. | 30 |
| AT-527 1100 mg (4x275 mg) Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5. | 30 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Pooled Placebo | AT-527 550 mg (1x550 mg) | AT-527 1100 mg (4x275 mg) | Total |
|---|---|---|---|---|
| Age, Continuous | 36.8 years STANDARD_DEVIATION 13.2 | 32.7 years STANDARD_DEVIATION 10.9 | 40.3 years STANDARD_DEVIATION 15.6 | 36.6 years STANDARD_DEVIATION 13.6 |
| Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA at Baseline | 6.24 log10 copies/mL STANDARD_DEVIATION 1.4 | 6.98 log10 copies/mL STANDARD_DEVIATION 1.1 | 5.94 log10 copies/mL STANDARD_DEVIATION 1.46 | 6.37 log10 copies/mL STANDARD_DEVIATION 1.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 1 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 26 Participants | 29 Participants | 91 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 38 Participants | 29 Participants | 28 Participants | 95 Participants |
| Sex: Female, Male Female | 22 Participants | 15 Participants | 17 Participants | 54 Participants |
| Sex: Female, Male Male | 18 Participants | 15 Participants | 13 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 1 / 40 | 1 / 30 | 5 / 30 |
| serious Total, serious adverse events | 1 / 40 | 1 / 30 | 1 / 30 |
Outcome results
Primary
Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 1100 mg and Pooled Placebo
SARS-CoV-2 virus RNA was measured by reverse-transcription polymerase chain reaction (RT-PCR) from NP swabs. The change from baseline was estimated from an ANCOVA model with baseline viral load as a covariate. Reported here is the adjusted mean change from baseline. A negative change from baseline indicates an improvement.
Time frame: Baseline, Day 3, Day 5, Day 7
Population: The modified ITT infected (mITTi) population was defined as all participants randomized in the study who received any amount of study drug and had at least one positive SARS-CoV-2 RT-PCR test result above or equal to the limit of quantification (LOQ) during the study, with participants grouped according to the treatment assignment at randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Matched to AT-527 550 mg | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 1100 mg and Pooled Placebo | Day 5 | -2.21 log10 copies/mL | Standard Error 0.205 |
| Placebo Matched to AT-527 550 mg | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 1100 mg and Pooled Placebo | Day 7 | -2.70 log10 copies/mL | Standard Error 0.207 |
| Placebo Matched to AT-527 550 mg | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 1100 mg and Pooled Placebo | Day 3 | -1.08 log10 copies/mL | Standard Error 0.19 |
| AT-527 550 mg (1x550 mg) | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 1100 mg and Pooled Placebo | Day 5 | -2.31 log10 copies/mL | Standard Error 0.231 |
| AT-527 550 mg (1x550 mg) | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 1100 mg and Pooled Placebo | Day 7 | -2.78 log10 copies/mL | Standard Error 0.236 |
| AT-527 550 mg (1x550 mg) | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 1100 mg and Pooled Placebo | Day 3 | -1.18 log10 copies/mL | Standard Error 0.223 |
Comparison: Day 3p-value: 0.735180% CI: [-0.48, 0.28]ANCOVA
Comparison: Day 5p-value: 0.752480% CI: [-0.5, 0.3]ANCOVA
Comparison: Day 7p-value: 0.808380% CI: [-0.48, 0.33]ANCOVA
Primary
Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 550 mg and Matched Placebo
SARS-CoV-2 virus RNA was measured by reverse-transcription polymerase chain reaction (RT-PCR) from nasopharyngeal (NP) swabs. The change from baseline was estimated from an ANCOVA model with baseline viral load as a covariate. Reported here is the adjusted mean change from baseline. A negative change from baseline indicates an improvement.
Time frame: Baseline, Day 3, Day 5, Day 7
Population: The modified ITT infected (mITTi) population was defined as all participants randomized in the study who received any amount of study drug and had at least one positive SARS-CoV-2 RT-PCR test result above or equal to the limit of quantification (LOQ) during the study, with participants grouped according to the treatment assignment at randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Matched to AT-527 550 mg | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 550 mg and Matched Placebo | Day 3 | -1.16 log10 copies/mL | Standard Error 0.203 |
| Placebo Matched to AT-527 550 mg | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 550 mg and Matched Placebo | Day 5 | -2.42 log10 copies/mL | Standard Error 0.23 |
| Placebo Matched to AT-527 550 mg | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 550 mg and Matched Placebo | Day 7 | -3.13 log10 copies/mL | Standard Error 0.22 |
| AT-527 550 mg (1x550 mg) | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 550 mg and Matched Placebo | Day 3 | -1.26 log10 copies/mL | Standard Error 0.206 |
| AT-527 550 mg (1x550 mg) | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 550 mg and Matched Placebo | Day 5 | -2.11 log10 copies/mL | Standard Error 0.226 |
| AT-527 550 mg (1x550 mg) | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 550 mg and Matched Placebo | Day 7 | -3.38 log10 copies/mL | Standard Error 0.22 |
Comparison: Day 3p-value: 0.714480% CI: [-0.49, 0.27]ANCOVA
Comparison: Day 5p-value: 0.337380% CI: [-0.11, 0.74]ANCOVA
Comparison: Day 7p-value: 0.42680% CI: [-0.66, 0.16]ANCOVA
Secondary
Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA
AUC is the amount of SARS-CoV-2 virus RNA from baseline to the last sample timepoint and was calculated using the trapezoidal method. RT-PCR was measured from NP swabs.
Time frame: Baseline, Day 3, Day 5, Day 7
Population: The mITTi population was defined as all participants randomized in the study who received any amount of study drug and had at least one positive SARS-CoV-2 RT-PCR test result above or equal to the limit of quantification (LOQ) during the study, with participants grouped according to the treatment assignment at randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matched to AT-527 550 mg | Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA | 651.56 log10 copies/mL*hour | Standard Deviation 189.1 |
| AT-527 550 mg (1x550 mg) | Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA | 733.70 log10 copies/mL*hour | Standard Deviation 146.63 |
| AT-527 1100 mg (4x275 mg) | Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA | 618.62 log10 copies/mL*hour | Standard Deviation 194.88 |
Secondary
Duration of Fever
Duration of fever was defined as the time from start of treatment to return to an afebrile state (temperature ≤ 37.5°C) maintained for at least 21.5 hours.
Time frame: Up to 28 Days
Population: The modified ITT infected (mITTi) population was defined as all participants randomized in the study who received any amount of study drug and had at least one positive SARS-CoV-2 RT-PCR test result above or equal to the limit of quantification (LOQ) during the study, with participants grouped according to the treatment assignment at randomization. Only participants who had a fever (temperature \> 37.5 degrees Celsius) at baseline are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Matched to AT-527 550 mg | Duration of Fever | 10.6 hours |
Secondary
Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints
Reported here is the percentage of participants with a positive virus RNA by RT-PCR test result above or equal to the limit of quantification (LOQ). RT-PCR was measured from NP swabs.
Time frame: Baseline, Day 3, Day 5, Day 7
Population: The mITTi population was defined as all participants randomized in the study who received any amount of study drug and had at least one positive SARS-CoV-2 RT-PCR test result above or equal to the limit of quantification (LOQ) during the study, with participants grouped according to the treatment assignment at randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Matched to AT-527 550 mg | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Day 3 | 95.0 percentage of participants |
| Placebo Matched to AT-527 550 mg | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Baseline | 100 percentage of participants |
| Placebo Matched to AT-527 550 mg | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Day 7 | 76.9 percentage of participants |
| Placebo Matched to AT-527 550 mg | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Day 5 | 84.2 percentage of participants |
| AT-527 550 mg (1x550 mg) | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Day 5 | 90.0 percentage of participants |
| AT-527 550 mg (1x550 mg) | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Day 7 | 79.3 percentage of participants |
| AT-527 550 mg (1x550 mg) | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Baseline | 100 percentage of participants |
| AT-527 550 mg (1x550 mg) | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Day 3 | 100 percentage of participants |
| AT-527 1100 mg (4x275 mg) | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Day 3 | 93.1 percentage of participants |
| AT-527 1100 mg (4x275 mg) | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Day 5 | 83.3 percentage of participants |
| AT-527 1100 mg (4x275 mg) | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Day 7 | 76.7 percentage of participants |
| AT-527 1100 mg (4x275 mg) | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Baseline | 96.7 percentage of participants |
Comparison: Day 380% CI: [-0.16, 10.16]
Comparison: Day 380% CI: [-9.2, 5.41]
Comparison: Day 580% CI: [-4.82, 16.4]
Comparison: Day 580% CI: [-12.4, 10.65]
Comparison: Day 780% CI: [-10.64, 15.42]
Comparison: Day 780% CI: [-13.39, 12.88]
Secondary
Percentage of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any of the following: any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the medicinal product, any new disease or exacerbation of an existing disease, recurrence of an intermittent medical condition not present at baseline or related to a protocol-mandated intervention.
Time frame: Up to 33 Days
Population: Safety population consisted of all participants who received any amount of study drug and were grouped according to the treatment that the participants actually received rather than the treatment assigned at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Matched to AT-527 550 mg | Percentage of Participants With Adverse Events (AEs) | 27.5 percentage of participants |
| AT-527 550 mg (1x550 mg) | Percentage of Participants With Adverse Events (AEs) | 20.0 percentage of participants |
| AT-527 1100 mg (4x275 mg) | Percentage of Participants With Adverse Events (AEs) | 33.3 percentage of participants |
Secondary
Percentage of Participants With COVID-19 Related Complications
COVID-19 related complications include death, hospitalization, radiologically confirmed pneumonia, acute respiratory failure, sepsis, coagulopathy, pericarditis, myocarditis, and cardiac failure.
Time frame: Up to 33 Days
Population: The mITTi population was defined as all participants randomized in the study who received any amount of study drug and had at least one positive SARS-CoV-2 RT-PCR test result above or equal to the limit of quantification (LOQ) during the study, with participants grouped according to the treatment assignment at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Matched to AT-527 550 mg | Percentage of Participants With COVID-19 Related Complications | 0 percentage of participants |
| AT-527 550 mg (1x550 mg) | Percentage of Participants With COVID-19 Related Complications | 3.3 percentage of participants |
| AT-527 1100 mg (4x275 mg) | Percentage of Participants With COVID-19 Related Complications | 3.3 percentage of participants |
Secondary
Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527
AT-511 is the free base form of AT-527. Its major metabolites are AT-551, AT-229, and AT-273.
Time frame: Day 1: pre-dose, 1 hour, 4 hours; Day 3: pre-dose; Day 5: pre-dose, 1 hour, 4 hours, 48 hours
Population: The pharmacokinetic-evaluable population consisted of all participants randomized into the study who had at least one post-dose drug concentration measurement at a scheduled visit timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-511: Day 1, pre-dose | 0.5 nanograms per milliliter (ng/mL) | Standard Deviation 0 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-511: Day 1, 1 hour | 3575.0 nanograms per milliliter (ng/mL) | Standard Deviation 2883.6 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-511: Day 1, 4 hours | 852.4 nanograms per milliliter (ng/mL) | Standard Deviation 1513.2 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-511: Day 3, pre-dose | 9.6 nanograms per milliliter (ng/mL) | Standard Deviation 15.9 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-511: Day 5, pre-dose | 316.7 nanograms per milliliter (ng/mL) | Standard Deviation 1544.7 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-511: Day 5, 1 hour | 3568.9 nanograms per milliliter (ng/mL) | Standard Deviation 3352.1 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-511: Day 5, 4 hours | 1323.3 nanograms per milliliter (ng/mL) | Standard Deviation 2883.5 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-511: Day 5, 48 hours | 0.6 nanograms per milliliter (ng/mL) | Standard Deviation 0.6 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-551: Day 1, pre-dose | 0.5 nanograms per milliliter (ng/mL) | Standard Deviation 0 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-551: Day 1, 1 hour | 592.2 nanograms per milliliter (ng/mL) | Standard Deviation 576.9 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-551: Day 1, 4 hours | 640.4 nanograms per milliliter (ng/mL) | Standard Deviation 446.3 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-551: Day 3, pre-dose | 84.0 nanograms per milliliter (ng/mL) | Standard Deviation 72.1 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-551: Day 5, pre-dose | 71.3 nanograms per milliliter (ng/mL) | Standard Deviation 61.6 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-551: Day 5, 1 hour | 302.8 nanograms per milliliter (ng/mL) | Standard Deviation 222.1 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-551: Day 5, 4 hours | 342.1 nanograms per milliliter (ng/mL) | Standard Deviation 254.9 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-551: Day 5, 48 hours | 4.4 nanograms per milliliter (ng/mL) | Standard Deviation 4.8 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-229: Day 1, pre-dose | 0.5 nanograms per milliliter (ng/mL) | Standard Deviation 0 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-229: Day 1, 1 hour | 371.9 nanograms per milliliter (ng/mL) | Standard Deviation 460.3 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-229: Day 1, 4 hours | 865.4 nanograms per milliliter (ng/mL) | Standard Deviation 494.2 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-229: Day 3, pre-dose | 682.8 nanograms per milliliter (ng/mL) | Standard Deviation 351.7 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-229: Day 5, pre-dose | 797.8 nanograms per milliliter (ng/mL) | Standard Deviation 459.9 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-229: Day 5, 1 hour | 990.9 nanograms per milliliter (ng/mL) | Standard Deviation 505.3 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-229: Day 5, 4 hours | 1357.2 nanograms per milliliter (ng/mL) | Standard Deviation 825.3 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-229: Day 5, 48 hours | 279.4 nanograms per milliliter (ng/mL) | Standard Deviation 285.3 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-273: Day 1, pre-dose | 0.5 nanograms per milliliter (ng/mL) | Standard Deviation 0 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-273: Day 1, 1 hour | 35.7 nanograms per milliliter (ng/mL) | Standard Deviation 47.4 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-273: Day 1, 4 hours | 231.8 nanograms per milliliter (ng/mL) | Standard Deviation 111.4 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-273: Day 3, pre-dose | 245.6 nanograms per milliliter (ng/mL) | Standard Deviation 122.8 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-273: Day 5, pre-dose | 263.6 nanograms per milliliter (ng/mL) | Standard Deviation 107.3 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-273: Day 5, 1 hour | 252.1 nanograms per milliliter (ng/mL) | Standard Deviation 97.4 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-273: Day 5, 4 hours | 310.6 nanograms per milliliter (ng/mL) | Standard Deviation 107.5 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 1100 mg AT-527 | AT-273: Day 5, 48 hours | 84.4 nanograms per milliliter (ng/mL) | Standard Deviation 45.5 |
Secondary
Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527
AT-511 is the free base form of AT-527. Its major metabolites are AT-551, AT-229, and AT-273.
Time frame: Day 1: pre-dose, 1 hour, 3 hours; Day 3: pre-dose; Day 5: pre-dose, 3 hours, 48 hours
Population: The pharmacokinetic-evaluable population consisted of all participants randomized into the study who had at least one post-dose drug concentration measurement at a scheduled visit timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-229: Day 5, 3 hours | 773.9 nanograms per milliliter (ng/mL) | Standard Deviation 340.8 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-229: Day 5, 48 hours | 89.2 nanograms per milliliter (ng/mL) | Standard Deviation 87.8 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-273: Day 5, pre-dose | 138.1 nanograms per milliliter (ng/mL) | Standard Deviation 53 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-273: Day 5, 3 hours | 236.9 nanograms per milliliter (ng/mL) | Standard Deviation 79.9 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-273: Day 5, 48 hours | 40.9 nanograms per milliliter (ng/mL) | Standard Deviation 22.7 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-511: Day 1, pre-dose | 1.3 nanograms per milliliter (ng/mL) | Standard Deviation 4.5 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-511: Day 1, 1 hour | 1950.5 nanograms per milliliter (ng/mL) | Standard Deviation 2365 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-511: Day 1, 3 hours | 441.4 nanograms per milliliter (ng/mL) | Standard Deviation 645.8 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-511: Day 3, pre-dose | 254.2 nanograms per milliliter (ng/mL) | Standard Deviation 943.1 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-511: Day 5, pre-dose | 5.6 nanograms per milliliter (ng/mL) | Standard Deviation 21.9 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-511: Day 5, 3 hours | 415.7 nanograms per milliliter (ng/mL) | Standard Deviation 445.5 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-511: Day 5, 48 hours | 0.5 nanograms per milliliter (ng/mL) | Standard Deviation 0 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-551: Day 1, pre-dose | 0.5 nanograms per milliliter (ng/mL) | Standard Deviation 0 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-551: Day 1, 1 hour | 347.5 nanograms per milliliter (ng/mL) | Standard Deviation 334.1 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-551: Day 1, 3 hours | 375.8 nanograms per milliliter (ng/mL) | Standard Deviation 303.9 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-551: Day 3, pre-dose | 56.9 nanograms per milliliter (ng/mL) | Standard Deviation 100.1 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-551: Day 5, pre-dose | 26.6 nanograms per milliliter (ng/mL) | Standard Deviation 22.7 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-551: Day 5, 3 hours | 323.8 nanograms per milliliter (ng/mL) | Standard Deviation 168.3 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-551: Day 5, 48 hours | 1.7 nanograms per milliliter (ng/mL) | Standard Deviation 1.4 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-229: Day 1, pre-dose | 0.5 nanograms per milliliter (ng/mL) | Standard Deviation 0 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-229: Day 1, 1 hour | 268.5 nanograms per milliliter (ng/mL) | Standard Deviation 318.5 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-229: Day 1, 3 hours | 427.4 nanograms per milliliter (ng/mL) | Standard Deviation 275.8 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-229: Day 3, pre-dose | 290.3 nanograms per milliliter (ng/mL) | Standard Deviation 152.3 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-229: Day 5, pre-dose | 295.4 nanograms per milliliter (ng/mL) | Standard Deviation 145 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-273: Day 1, pre-dose | 0.5 nanograms per milliliter (ng/mL) | Standard Deviation 0 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-273: Day 1, 1 hour | 26.5 nanograms per milliliter (ng/mL) | Standard Deviation 29 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-273: Day 1, 3 hours | 132.2 nanograms per milliliter (ng/mL) | Standard Deviation 66.7 |
| Placebo Matched to AT-527 550 mg | Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated With 550 mg AT-527 | AT-273: Day 3, pre-dose | 135.9 nanograms per milliliter (ng/mL) | Standard Deviation 47.6 |
Secondary
Time to Alleviation of an Individual Symptom
The COVID-19 Symptom Diary included the following 14 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, diarrhea, sense of smell over the past 7 days and sense of taste over the past 7 days. The severity of items 1-12 was recorded on a 4-point Likert scale (none=0, mild=1, moderate=2, severe=3). Items 13-14 were recorded on a 3-point Likert scale (same as usual=0, less than usual=1, no sense=2). Time to alleviation of an individual symptom was defined as the time taken from the start of treatment to the point at which the following criterion was met and maintained (for each individual symptom) for at least 21.5 hours: score of 0 or 1 for Items 1-12 of the COVID-19 Symptom Diary; score of 0 for Items 13 and 14 of the COVID-19 Symptom Diary.
Time frame: Up to 28 Days
Population: The mITTi population was defined as all participants randomized in the study who received any amount of study drug and had at least one positive SARS-CoV-2 RT-PCR test result above or equal to the limit of quantification (LOQ) during the study, with participants grouped according to the treatment assignment at randomization. Only participants with a baseline score of \> 1 for Items 1 - 12 or \> 0 for Items 13 - 14 of the COVID-19 Symptom Diary were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo Matched to AT-527 550 mg | Time to Alleviation of an Individual Symptom | Vomiting | NA hours |
| Placebo Matched to AT-527 550 mg | Time to Alleviation of an Individual Symptom | Headache | 32.0 hours |
| Placebo Matched to AT-527 550 mg | Time to Alleviation of an Individual Symptom | Sense of Smell | 261.5 hours |
| Placebo Matched to AT-527 550 mg | Time to Alleviation of an Individual Symptom | Chills/Sweats | 11.8 hours |
| Placebo Matched to AT-527 550 mg | Time to Alleviation of an Individual Symptom | Cough | 22.6 hours |
| Placebo Matched to AT-527 550 mg | Time to Alleviation of an Individual Symptom | Nausea | NA hours |
| Placebo Matched to AT-527 550 mg | Time to Alleviation of an Individual Symptom | Feeling Hot or Feverish | 26.5 hours |
| Placebo Matched to AT-527 550 mg | Time to Alleviation of an Individual Symptom | Sore Throat | 20.5 hours |
| Placebo Matched to AT-527 550 mg | Time to Alleviation of an Individual Symptom | Shortness of Breath | 23.9 hours |
| Placebo Matched to AT-527 550 mg | Time to Alleviation of an Individual Symptom | Nasal Congestion/Runny Nose | 27.6 hours |
| Placebo Matched to AT-527 550 mg | Time to Alleviation of an Individual Symptom | Sense of Taste | 221.1 hours |
| Placebo Matched to AT-527 550 mg | Time to Alleviation of an Individual Symptom | Aches and Pains | 33.1 hours |
| Placebo Matched to AT-527 550 mg | Time to Alleviation of an Individual Symptom | Diarrhea | NA hours |
| Placebo Matched to AT-527 550 mg | Time to Alleviation of an Individual Symptom | Fatigue | 47.8 hours |
| AT-527 550 mg (1x550 mg) | Time to Alleviation of an Individual Symptom | Aches and Pains | 22.3 hours |
| AT-527 550 mg (1x550 mg) | Time to Alleviation of an Individual Symptom | Nasal Congestion/Runny Nose | 34.2 hours |
| AT-527 550 mg (1x550 mg) | Time to Alleviation of an Individual Symptom | Sore Throat | 24.1 hours |
| AT-527 550 mg (1x550 mg) | Time to Alleviation of an Individual Symptom | Cough | 90.7 hours |
| AT-527 550 mg (1x550 mg) | Time to Alleviation of an Individual Symptom | Shortness of Breath | 68.9 hours |
| AT-527 550 mg (1x550 mg) | Time to Alleviation of an Individual Symptom | Headache | 11.7 hours |
| AT-527 550 mg (1x550 mg) | Time to Alleviation of an Individual Symptom | Chills/Sweats | 12.0 hours |
| AT-527 550 mg (1x550 mg) | Time to Alleviation of an Individual Symptom | Sense of Smell | 290.2 hours |
| AT-527 550 mg (1x550 mg) | Time to Alleviation of an Individual Symptom | Sense of Taste | 214.1 hours |
| AT-527 550 mg (1x550 mg) | Time to Alleviation of an Individual Symptom | Fatigue | 44.4 hours |
| AT-527 550 mg (1x550 mg) | Time to Alleviation of an Individual Symptom | Feeling Hot or Feverish | 48.0 hours |
| AT-527 1100 mg (4x275 mg) | Time to Alleviation of an Individual Symptom | Diarrhea | 9.8 hours |
| AT-527 1100 mg (4x275 mg) | Time to Alleviation of an Individual Symptom | Sore Throat | 111.7 hours |
| AT-527 1100 mg (4x275 mg) | Time to Alleviation of an Individual Symptom | Shortness of Breath | 11.6 hours |
| AT-527 1100 mg (4x275 mg) | Time to Alleviation of an Individual Symptom | Sense of Smell | 213.1 hours |
| AT-527 1100 mg (4x275 mg) | Time to Alleviation of an Individual Symptom | Sense of Taste | 178.5 hours |
| AT-527 1100 mg (4x275 mg) | Time to Alleviation of an Individual Symptom | Cough | 33.9 hours |
| AT-527 1100 mg (4x275 mg) | Time to Alleviation of an Individual Symptom | Headache | 34.4 hours |
| AT-527 1100 mg (4x275 mg) | Time to Alleviation of an Individual Symptom | Nasal Congestion/Runny Nose | 32.7 hours |
| AT-527 1100 mg (4x275 mg) | Time to Alleviation of an Individual Symptom | Feeling Hot or Feverish | 40.3 hours |
| AT-527 1100 mg (4x275 mg) | Time to Alleviation of an Individual Symptom | Chills/Sweats | 25.0 hours |
| AT-527 1100 mg (4x275 mg) | Time to Alleviation of an Individual Symptom | Fatigue | 70.6 hours |
| AT-527 1100 mg (4x275 mg) | Time to Alleviation of an Individual Symptom | Aches and Pains | 94.4 hours |
Secondary
Time to Alleviation of COVID-19 Symptoms (21.5 Hours)
COVID-19 symptoms were evaluated using the first 12 items in the COVID-19 Symptom Diary, which included the following 12 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, and diarrhea. The symptoms were scored on the 4-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe). Time to alleviation of COVID-19 symptoms is defined as the length of time taken from start of treatment to the point at which the following criterion is met and maintained for at least 21.5 hours: Score of 0 or 1 on Items 1-12 of the COVID-19 Symptom Diary, regardless of if the symptom is pre-existing or new.
Time frame: Up to 28 Days
Population: The mITTi population was defined as all participants randomized in the study who received any amount of study drug and had at least one positive SARS-CoV-2 RT-PCR test result above or equal to the limit of quantification (LOQ) during the study, with participants grouped according to the treatment assignment at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Matched to AT-527 550 mg | Time to Alleviation of COVID-19 Symptoms (21.5 Hours) | 43.4 hours |
| AT-527 550 mg (1x550 mg) | Time to Alleviation of COVID-19 Symptoms (21.5 Hours) | 57.2 hours |
| AT-527 1100 mg (4x275 mg) | Time to Alleviation of COVID-19 Symptoms (21.5 Hours) | 56.4 hours |
Secondary
Time to Alleviation of COVID-19 Symptoms (43 Hours)
COVID-19 symptoms were evaluated using the first 12 items in the COVID-19 Symptom Diary, which included the following 12 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, and diarrhea. The symptoms were scored on the 4-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe). Time to alleviation of COVID-19 symptoms is defined as the length of time taken from start of treatment to the point at which the following criterion is met and maintained for at least 43 hours: Score of 0 or 1 on Items 1-12 of the COVID-19 Symptom Diary, regardless of if the symptom is pre-existing or new.
Time frame: Up to 28 Days
Population: The mITTi population was defined as all participants randomized in the study who received any amount of study drug and had at least one positive SARS-CoV-2 RT-PCR test result above or equal to the limit of quantification (LOQ) during the study, with participants grouped according to the treatment assignment at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Matched to AT-527 550 mg | Time to Alleviation of COVID-19 Symptoms (43 Hours) | 43.4 hours |
| AT-527 550 mg (1x550 mg) | Time to Alleviation of COVID-19 Symptoms (43 Hours) | 57.2 hours |
| AT-527 1100 mg (4x275 mg) | Time to Alleviation of COVID-19 Symptoms (43 Hours) | 58.1 hours |
Secondary
Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours)
COVID-19 symptoms were evaluated using the first 12 items in the COVID-19 Symptom Diary, which included the following 12 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, and diarrhea. The symptoms were scored on the 4-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe).Time to alleviation or improvement is defined as the length of time taken from start of treatment to the point at which all of the following three criteria are met and maintained for a concurrent duration of at least 21.5 hours: new symptoms with a score of 0 or 1; pre- existing and worsened due to COVID-19 symptoms with at least a single category improvement from baseline; pre-existing and not worsened due to COVID-19 symptoms remaining the same or at least a single category improvement from baseline.
Time frame: Up to 28 Days
Population: The mITTi population was defined as all participants randomized in the study who received any amount of study drug and had at least one positive SARS-CoV-2 RT-PCR test result above or equal to the limit of quantification (LOQ) during the study, with participants grouped according to the treatment assignment at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Matched to AT-527 550 mg | Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours) | 43.4 hours |
| AT-527 550 mg (1x550 mg) | Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours) | 57.2 hours |
| AT-527 1100 mg (4x275 mg) | Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours) | 56.4 hours |
Secondary
Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours)
COVID-19 symptoms were evaluated using the first 12 items in the COVID-19 Symptom Diary, which included the following 12 items: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills/sweats, feeling hot or feverish, nausea, vomiting, and diarrhea. The symptoms were scored on the 4-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe). Time to alleviation or improvement is defined as the length of time taken from start of treatment to the point at which all of the following three criteria are met and maintained for a concurrent duration of at least 43 hours: new symptoms with a score of 0 or 1; pre- existing and worsened due to COVID-19 symptoms with at least a single category improvement from baseline; pre-existing and not worsened due to COVID-19 symptoms remaining the same or at least a single category improvement from baseline.
Time frame: Up to 28 Days
Population: The mITTi population was defined as all participants randomized in the study who received any amount of study drug and had at least one positive SARS-CoV-2 RT-PCR test result above or equal to the limit of quantification (LOQ) during the study, with participants grouped according to the treatment assignment at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Matched to AT-527 550 mg | Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours) | 43.4 hours |
| AT-527 550 mg (1x550 mg) | Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours) | 57.2 hours |
| AT-527 1100 mg (4x275 mg) | Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours) | 58.1 hours |
Secondary
Time to Cessation of SARS-CoV-2 Viral Shedding
Time to cessation of viral shedding was defined as the time between the initiation of any study treatment and the first time when a negative or below the limit of detection RT-PCR test result was obtained. RT-PCR was measured from NP swabs. Median, 25th and 75th percentiles were estimated from the Kaplan-Meier curve.
Time frame: Up to Day 7
Population: The mITTi population was defined as all participants randomized in the study who received any amount of study drug and had at least one positive SARS-CoV-2 RT-PCR test result above or equal to the limit of quantification (LOQ) during the study, with participants grouped according to the treatment assignment at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Matched to AT-527 550 mg | Time to Cessation of SARS-CoV-2 Viral Shedding | NA hours |
| AT-527 550 mg (1x550 mg) | Time to Cessation of SARS-CoV-2 Viral Shedding | NA hours |
| AT-527 1100 mg (4x275 mg) | Time to Cessation of SARS-CoV-2 Viral Shedding | NA hours |
80% CI: [0.53, 1.74]
80% CI: [0.76, 2.32]
Secondary
Time to Sustained Non-Detectable SARS-CoV-2 Virus RNA
Time to sustained non-detectable SARS-CoV-2 virus RNA was defined as the time between the initiation of any study treatment and first time when a negative or below the limit of detection test result by RT-PCR is obtained after which no positive test above or equal to the limit of detection was reported. RT-PCR was measured from NP swabs. Median, 25th and 75th percentiles were estimated from the Kaplan-Meier curve.
Time frame: Up to Day 7
Population: The mITTi population was defined as all participants randomized in the study who received any amount of study drug and had at least one positive SARS-CoV-2 RT-PCR test result above or equal to the limit of quantification (LOQ) during the study, with participants grouped according to the treatment assignment at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Matched to AT-527 550 mg | Time to Sustained Non-Detectable SARS-CoV-2 Virus RNA | NA hours |
| AT-527 550 mg (1x550 mg) | Time to Sustained Non-Detectable SARS-CoV-2 Virus RNA | NA hours |
| AT-527 1100 mg (4x275 mg) | Time to Sustained Non-Detectable SARS-CoV-2 Virus RNA | NA hours |
80% CI: [0.44, 1.7]
80% CI: [0.56, 2.03]