COVID-19
Conditions
Keywords
Coronavirus Disease 2019; COVID-19; antiviral drug; SARS-CoV-2; Mild to Moderate COVID-19; antiviral efficacy
Brief summary
This study will evaluate the efficacy, safety, antiviral activity, and pharmacokinetics of study drug RO7496998 (AT-527) compared to placebo in non-hospitalized adult and adolescent participants with mild to moderate coronavirus disease 2019 (COVID-19) in the outpatient setting.
Interventions
DRUGRO7496998
275 mg tablets
DRUGPlacebo
Matching tablets
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
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Positive SARS-CoV-2 diagnostic test (RT-PCR or validated rapid antigen test) ≤72 hours prior to randomization * At least three of the following symptoms of at least moderate (score ≥2 as per COVID-19 Symptom Diary) intensity: nasal congestion or runny nose, sore throat, cough, shortness of breath, muscle or body aches, fatigue, headache, chills or sweats, feeling hot or feverish, nausea, vomiting, or diarrhea. * Has symptoms consistent with mild or moderate COVID-19, as determined by the investigator, with onset ≤5 days before dosing on Day 1
Exclusion criteria
* Clinical signs indicative of COVID-19 illness requiring hospitalization * Admitted to a hospital prior to randomization or is hospitalized (inpatient) at randomization due to COVID-19 * In the opinion of the investigator, is likely to experience imminent deterioration and require hospitalization * Treatment with an investigational drug within 5 half-lives or 3 months (whichever is longer) of randomization * Treatment with a COVID-19 therapeutic agent including, but not limited to, other direct or indirect acting antivirals against SARS-CoV-2 (such as remdesivir or favipiravir), systemic or inhaled steroids (such as dexamethasone or inhaled budesonide), colchicine, ivermectin, interferons, convalescent plasma, monoclonal antibodies against SARS CoV-2 or interleukin 6 (IL-6), intravenous immunoglobulin or other EUA-approved treatments within 3 months or less than 5 drug elimination half-lives (whichever is longer) prior to the screening visit * Concomitant use of P-glycoprotein inhibitors or inducers listed as prohibited therapy in the protocol * Known allergy or hypersensitivity to components of study drug * Abnormal laboratory test results at screening * Requirement of any prohibited medications during the study * Other known active viral or bacterial infection at the time of screening, such as influenza * Any clinically significant medical condition or laboratory abnormality that, in the opinion of the investigator, could jeopardize the safety of the patient or affect patient compliance or safety/efficacy observations during the study * COVID-19 vaccination within ≤ 40-days prior to enrollment (second dose if applicable)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours) | Up to 29 days | COVID-19 symptoms will be evaluated using the COVID-19 Symptom Diary (questions 1-12). The severity of each COVID-19 symptom will be recorded on a Likert scale (i.e none/mild/moderate/severe). The time to alleviation or improvement of COVID-19 symptoms is defined as follows: for new symptoms, it is defined as the length of time taken from randomization to the point at which a Score of 0 or 1 has been maintained for a duration of at least 21.5 hours. For preexisting symptoms, it is defined as the time from randomization to when a patient's symptoms have been maintained or improved (requires at least a single category improvement from baseline on the COVID-19 Symptom Diary Likert scale) for a duration of 21.5 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Alleviation of COVID-19 Symptoms (21.5 Hours) | Up to 29 days | Time from randomization 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. |
| Time to Alleviation of COVID-19 Symptoms (43 Hours) | Up to 29 days | Time from randomization 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. |
| Time to One-Category Improvement of Baseline Presenting COVID-19 Symptoms | Up to 29 days | Time from randomization to the point at which symptoms (Items 1-12 of the COVID-19 Symptom Diary) have improved by at least one category from baseline on the COVID-19 Symptom Diary Likert scale, maintained for at least 21.5 hours. |
| Time to Alleviation of Individual Symptoms | Up to 29 days | Time from randomization to the point at which the following criterion is met and maintained (for each individual symptom) for at least 21.5 hours. \- Score of 0 or 1 for Items 1-14 of the COVID-19 Symptom Diary |
| Percentage of Participants Requiring Hospitalization for COVID-19 | Up to Day 33 visit | Hospitalizations for COVID-19 are defined as SAEs for which the investigator has cited that the suspected cause was the disease under study and where there is a non-missing hospital admission date. |
| Percentage of Participants With Greater Than or Equal to 1 COVID-19 Related Medically Attended Visit | Up to Day 33 visit | Medically attended visit is defined as hospitalization, emergency room (ER) visit, urgent care visit, physician's office visit, or telemedicine visit, with the primary reason for the visit being COVID-19. |
| Duration of Fever | Up to 29 days | Time to return to an afebrile state (temperature ≤ 37.5°C) maintained for at least 21.5 hours. |
| Percentage of Participants With COVID-19 Related Complications | Up to Day 33 visit | COVID-related complications are defined as death, hospitalization, pneumonia, sepsis, coagulopathy, pericarditis/myocarditis and cardiac failure. Pneumonia, acute respiratory failure, sepsis, coagulopathy, pericarditis/myocarditis, and cardiac failure were adjudicated per blinded manual medical review of events by an internal adjudication team before study readout. |
| Percentage of Participants With Any Post-Treatment Infection | Up to Day 33 visit | Post-treatment infections were defined as any treatment-emergent adverse event with a primary system organ class of infections and infestations. |
| Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours) | Up to 29 days | COVID-19 symptoms will be evaluated using the COVID-19 Symptom Diary (questions 1-12). The severity of each COVID-19 symptom will be recorded on a Likert scale (i.e none/mild/moderate/severe). The time to alleviation or improvement of COVID-19 symptoms is defined as follows: for new symptoms, it is defined as the length of time taken from randomization to the point at which a Score of 0 or 1 has been maintained for a duration of at least 43 hours. For preexisting symptoms, it is defined as the time from randomization to when a patient's symptoms have been maintained or improved (requires at least a single category improvement from baseline on the COVID-19 Symptom Diary Likert scale) for a duration of 43 hours. |
| Time to Cessation of SARS-CoV-2 Viral Shedding | Up to 14 days | Defined as time from randomization to the first time when a negative qualitative virus RNA by RT-PCR test result is obtained. |
| Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Baseline and on Days 3, 5, 7 and 14 | Defined as percentage of participants with a positive qualitative virus RNA by RT-PCR. |
| Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA | Day 1 prior to dosing, Day 3, Day 5, Day 7 and Day 14 | — |
| Percentage of Participants With Adverse Events (AEs) | Up to Day 33 visit | — |
| Plasma Concentration of AT-511 at Specified Timepoints | Up to 7 days | AT-511 is the free base form of RO7496998 (AT-527). |
| Plasma Concentration of AT-551 at Specified Timepoints | Up to 7 days | AT-511 is the free base form of RO7496998 (AT-527). Major metabolites are AT-551, AT-229, and AT-273 (a surrogate for the intracellular concentration of the active triphosphate metabolite AT-9010) |
| Plasma Concentration of AT-229 at Specified Timepoints | Up to 7 days | AT-511 is the free base form of RO7496998 (AT-527). Major metabolites are AT-551, AT-229, and AT-273 (a surrogate for the intracellular concentration of the active triphosphate metabolite AT-9010) |
| Plasma Concentration of AT-273 at Specified Timepoints | Up to 7 days | AT-511 is the free base form of RO7496998 (AT-527). Major metabolites are AT-551, AT-229, and AT-273 (a surrogate for the intracellular concentration of the active triphosphate metabolite AT-9010) |
| Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA | Baseline and on Days 3, 5, 7 and 14 | SARS-CoV-2 virus RNA will be measured by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) |
Countries
Argentina, Belgium, Brazil, Denmark, Germany, Japan, Mexico, Portugal, Romania, Switzerland, Turkey (Türkiye), Ukraine
Participant flow
Recruitment details
Participants were non-hospitalized, with mild to moderate COVID-19, with or without risk factors for severe disease.
Participants by arm
| Arm | Count |
|---|---|
| Placebo The dose and regimen of the placebo will match that of AT-527. | 73 |
| RO7496998 (AT-527) Orally administered, 550 mg twice daily (BID) for 5 days | 143 |
| Total | 216 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Placebo | RO7496998 (AT-527) | Total |
|---|---|---|---|
| Age, Continuous | 41.7 years STANDARD_DEVIATION 14.9 | 41.1 years STANDARD_DEVIATION 13.2 | 41.3 years STANDARD_DEVIATION 13.7 |
| Number of COVID-19 Symptoms Present at Baseline | 7.85 Number of Covid-19 Symptoms STANDARD_DEVIATION 2.58 | 7.92 Number of Covid-19 Symptoms STANDARD_DEVIATION 2.74 | 7.90 Number of Covid-19 Symptoms STANDARD_DEVIATION 2.68 |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants | 9 Participants | 15 Participants |
| Race (NIH/OMB) Asian | 14 Participants | 26 Participants | 40 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 50 Participants | 105 Participants | 155 Participants |
| Sex: Female, Male Female | 32 Participants | 62 Participants | 94 Participants |
| Sex: Female, Male Male | 41 Participants | 81 Participants | 122 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 71 | 0 / 141 |
| other Total, other adverse events | 5 / 71 | 11 / 141 |
| serious Total, serious adverse events | 7 / 71 | 5 / 141 |
Outcome results
Primary
Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours)
COVID-19 symptoms will be evaluated using the COVID-19 Symptom Diary (questions 1-12). The severity of each COVID-19 symptom will be recorded on a Likert scale (i.e none/mild/moderate/severe). The time to alleviation or improvement of COVID-19 symptoms is defined as follows: for new symptoms, it is defined as the length of time taken from randomization to the point at which a Score of 0 or 1 has been maintained for a duration of at least 21.5 hours. For preexisting symptoms, it is defined as the time from randomization to when a patient's symptoms have been maintained or improved (requires at least a single category improvement from baseline on the COVID-19 Symptom Diary Likert scale) for a duration of 21.5 hours.
Time frame: Up to 29 days
Population: All participants who were randomized to treatment, received a dose of study treatment, and were RT-qPCR positive for SARS-CoV-2 at any point during the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours) | 73.7 hours |
| RO7496998 (AT-527) | Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours) | 94.5 hours |
Secondary
Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA
Time frame: Day 1 prior to dosing, Day 3, Day 5, Day 7 and Day 14
Population: All participants who were randomized to treatment, received a dose of study treatment, were RT-qPCR positive for SARS-CoV-2 at any point during the study, and had at least 2 or more virology assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA | 1122.39 log10 copies/mL*hour | Standard Deviation 339.7 |
| RO7496998 (AT-527) | Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA | 1174.30 log10 copies/mL*hour | Standard Deviation 377.49 |
Secondary
Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA
SARS-CoV-2 virus RNA will be measured by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR)
Time frame: Baseline and on Days 3, 5, 7 and 14
Population: All participants who were randomized to treatment, received a dose of study treatment, and were RT-qPCR positive for SARS-CoV-2 at any point during the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA | Day 3 | -1.05 log10 copies/mL | Standard Deviation 1.06 |
| Placebo | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA | Day 7 | -3.10 log10 copies/mL | Standard Deviation 1.38 |
| Placebo | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA | Day 5 | -2.24 log10 copies/mL | Standard Deviation 1.4 |
| Placebo | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA | Day 14 | -4.21 log10 copies/mL | Standard Deviation 1.64 |
| Placebo | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA | Baseline | 6.49 log10 copies/mL | Standard Deviation 1.61 |
| RO7496998 (AT-527) | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA | Day 14 | -4.25 log10 copies/mL | Standard Deviation 1.64 |
| RO7496998 (AT-527) | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA | Baseline | 6.59 log10 copies/mL | Standard Deviation 1.54 |
| RO7496998 (AT-527) | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA | Day 3 | -1.07 log10 copies/mL | Standard Deviation 1.16 |
| RO7496998 (AT-527) | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA | Day 5 | -2.01 log10 copies/mL | Standard Deviation 1.5 |
| RO7496998 (AT-527) | Change From Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA | Day 7 | -2.98 log10 copies/mL | Standard Deviation 1.66 |
Secondary
Duration of Fever
Time to return to an afebrile state (temperature ≤ 37.5°C) maintained for at least 21.5 hours.
Time frame: Up to 29 days
Population: All participants who were randomized to treatment, received a dose of study treatment, were RT-qPCR positive for SARS-CoV-2 at any point during the study, and had a fever at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Duration of Fever | 47.3 hours |
| RO7496998 (AT-527) | Duration of Fever | 55.7 hours |
Secondary
Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints
Defined as percentage of participants with a positive qualitative virus RNA by RT-PCR.
Time frame: Baseline and on Days 3, 5, 7 and 14
Population: All participants who were randomized to treatment, received a dose of study treatment, and were RT-qPCR positive for SARS-CoV-2 at any point during the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Baseline | 97.1 percentage of participants |
| Placebo | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Day 7 | 74.6 percentage of participants |
| Placebo | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Day 3 | 98.5 percentage of participants |
| Placebo | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Day 14 | 43.9 percentage of participants |
| Placebo | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Day 5 | 89.7 percentage of participants |
| RO7496998 (AT-527) | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Day 14 | 34.4 percentage of participants |
| RO7496998 (AT-527) | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Baseline | 100 percentage of participants |
| RO7496998 (AT-527) | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Day 5 | 91.9 percentage of participants |
| RO7496998 (AT-527) | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Day 7 | 76.3 percentage of participants |
| RO7496998 (AT-527) | Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints | Day 3 | 96.4 percentage of participants |
Secondary
Percentage of Participants Requiring Hospitalization for COVID-19
Hospitalizations for COVID-19 are defined as SAEs for which the investigator has cited that the suspected cause was the disease under study and where there is a non-missing hospital admission date.
Time frame: Up to Day 33 visit
Population: All participants who were randomized to treatment, received a dose of study treatment, and were RT-qPCR positive for SARS-CoV-2 at any point during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Requiring Hospitalization for COVID-19 | 10.0 percentage of participants |
| RO7496998 (AT-527) | Percentage of Participants Requiring Hospitalization for COVID-19 | 2.9 percentage of participants |
Secondary
Percentage of Participants With Adverse Events (AEs)
Time frame: Up to Day 33 visit
Population: All participants who received at least one dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Adverse Events (AEs) | 36.6 percentage of participants |
| RO7496998 (AT-527) | Percentage of Participants With Adverse Events (AEs) | 39.0 percentage of participants |
Secondary
Percentage of Participants With Any Post-Treatment Infection
Post-treatment infections were defined as any treatment-emergent adverse event with a primary system organ class of infections and infestations.
Time frame: Up to Day 33 visit
Population: All participants who were randomized to treatment, received a dose of study treatment, and were RT-qPCR positive for SARS-CoV-2 at any point during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Any Post-Treatment Infection | 14.3 percentage of participants |
| RO7496998 (AT-527) | Percentage of Participants With Any Post-Treatment Infection | 9.5 percentage of participants |
Secondary
Percentage of Participants With COVID-19 Related Complications
COVID-related complications are defined as death, hospitalization, pneumonia, sepsis, coagulopathy, pericarditis/myocarditis and cardiac failure. Pneumonia, acute respiratory failure, sepsis, coagulopathy, pericarditis/myocarditis, and cardiac failure were adjudicated per blinded manual medical review of events by an internal adjudication team before study readout.
Time frame: Up to Day 33 visit
Population: All participants who were randomized to treatment, received a dose of study treatment, and were RT-qPCR positive for SARS-CoV-2 at any point during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With COVID-19 Related Complications | 10.0 percentage of participants |
| RO7496998 (AT-527) | Percentage of Participants With COVID-19 Related Complications | 4.4 percentage of participants |
Secondary
Percentage of Participants With Greater Than or Equal to 1 COVID-19 Related Medically Attended Visit
Medically attended visit is defined as hospitalization, emergency room (ER) visit, urgent care visit, physician's office visit, or telemedicine visit, with the primary reason for the visit being COVID-19.
Time frame: Up to Day 33 visit
Population: All participants who were randomized to treatment, received a dose of study treatment, and were RT-qPCR positive for SARS-CoV-2 at any point during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Greater Than or Equal to 1 COVID-19 Related Medically Attended Visit | 14.3 percentage of participants |
| RO7496998 (AT-527) | Percentage of Participants With Greater Than or Equal to 1 COVID-19 Related Medically Attended Visit | 10.2 percentage of participants |
Secondary
Plasma Concentration of AT-229 at Specified Timepoints
AT-511 is the free base form of RO7496998 (AT-527). Major metabolites are AT-551, AT-229, and AT-273 (a surrogate for the intracellular concentration of the active triphosphate metabolite AT-9010)
Time frame: Up to 7 days
Population: All participants who received AT-527 and had at least one post-dose drug concentration measurement at a scheduled visit time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentration of AT-229 at Specified Timepoints | Day 1, 0 hour | 2.2 nanograms per milliliter (ng/mL) | Standard Deviation 18.4 |
| Placebo | Plasma Concentration of AT-229 at Specified Timepoints | Day 1, 1 hour | 123.6 nanograms per milliliter (ng/mL) | Standard Deviation 172.5 |
| Placebo | Plasma Concentration of AT-229 at Specified Timepoints | Day 1, 2 hours | 507.8 nanograms per milliliter (ng/mL) | Standard Deviation 497.5 |
| Placebo | Plasma Concentration of AT-229 at Specified Timepoints | Day 1, 4 hours | 354.4 nanograms per milliliter (ng/mL) | Standard Deviation 259.2 |
| Placebo | Plasma Concentration of AT-229 at Specified Timepoints | Day 5, 0 hour | 367.8 nanograms per milliliter (ng/mL) | Standard Deviation 259.1 |
| Placebo | Plasma Concentration of AT-229 at Specified Timepoints | Day 5, 1 hour | 418.0 nanograms per milliliter (ng/mL) | Standard Deviation 257.6 |
| Placebo | Plasma Concentration of AT-229 at Specified Timepoints | Day 5, 2 hours | 454.3 nanograms per milliliter (ng/mL) | Standard Deviation 331.7 |
| Placebo | Plasma Concentration of AT-229 at Specified Timepoints | Day 5, 4 hours | 490.1 nanograms per milliliter (ng/mL) | Standard Deviation 296.4 |
| Placebo | Plasma Concentration of AT-229 at Specified Timepoints | Day 5, 8 hours | 279.6 nanograms per milliliter (ng/mL) | Standard Deviation 176 |
| Placebo | Plasma Concentration of AT-229 at Specified Timepoints | Day 5, 48 hours | 118.7 nanograms per milliliter (ng/mL) | Standard Deviation 127.2 |
Secondary
Plasma Concentration of AT-273 at Specified Timepoints
AT-511 is the free base form of RO7496998 (AT-527). Major metabolites are AT-551, AT-229, and AT-273 (a surrogate for the intracellular concentration of the active triphosphate metabolite AT-9010)
Time frame: Up to 7 days
Population: All participants who received AT-527 and had at least one post-dose drug concentration measurement at a scheduled visit time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentration of AT-273 at Specified Timepoints | Day 1, 0 hour | 0.7 nanograms per milliliter (ng/mL) | Standard Deviation 2.5 |
| Placebo | Plasma Concentration of AT-273 at Specified Timepoints | Day 1, 1 hour | 15.5 nanograms per milliliter (ng/mL) | Standard Deviation 26.9 |
| Placebo | Plasma Concentration of AT-273 at Specified Timepoints | Day 1, 2 hours | 135.1 nanograms per milliliter (ng/mL) | Standard Deviation 136.2 |
| Placebo | Plasma Concentration of AT-273 at Specified Timepoints | Day 1, 4 hours | 173.5 nanograms per milliliter (ng/mL) | Standard Deviation 120.6 |
| Placebo | Plasma Concentration of AT-273 at Specified Timepoints | Day 5, 0 hour | 149.8 nanograms per milliliter (ng/mL) | Standard Deviation 78.1 |
| Placebo | Plasma Concentration of AT-273 at Specified Timepoints | Day 5, 1 hour | 141.7 nanograms per milliliter (ng/mL) | Standard Deviation 72.7 |
| Placebo | Plasma Concentration of AT-273 at Specified Timepoints | Day 5, 2 hours | 108.8 nanograms per milliliter (ng/mL) | Standard Deviation 61 |
| Placebo | Plasma Concentration of AT-273 at Specified Timepoints | Day 5, 4 hours | 172.7 nanograms per milliliter (ng/mL) | Standard Deviation 129.2 |
| Placebo | Plasma Concentration of AT-273 at Specified Timepoints | Day 5, 8 hours | 118.6 nanograms per milliliter (ng/mL) | Standard Deviation 80.2 |
| Placebo | Plasma Concentration of AT-273 at Specified Timepoints | Day 5, 48 hours | 48.4 nanograms per milliliter (ng/mL) | Standard Deviation 32.7 |
Secondary
Plasma Concentration of AT-511 at Specified Timepoints
AT-511 is the free base form of RO7496998 (AT-527).
Time frame: Up to 7 days
Population: All participants who received AT-527 and had at least one post-dose drug concentration measurement at a scheduled visit time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentration of AT-511 at Specified Timepoints | Day 1, 0 hour | 17.4 nanograms per milliliter (ng/mL) | Standard Deviation 158.6 |
| Placebo | Plasma Concentration of AT-511 at Specified Timepoints | Day 1, 1 hour | 1456.8 nanograms per milliliter (ng/mL) | Standard Deviation 1757.7 |
| Placebo | Plasma Concentration of AT-511 at Specified Timepoints | Day 1, 2 hours | 1029.3 nanograms per milliliter (ng/mL) | Standard Deviation 1085.5 |
| Placebo | Plasma Concentration of AT-511 at Specified Timepoints | Day 1, 4 hours | 206.3 nanograms per milliliter (ng/mL) | Standard Deviation 289.5 |
| Placebo | Plasma Concentration of AT-511 at Specified Timepoints | Day 5, 0 hour | 52.8 nanograms per milliliter (ng/mL) | Standard Deviation 271 |
| Placebo | Plasma Concentration of AT-511 at Specified Timepoints | Day 5, 1 hour | 1659.0 nanograms per milliliter (ng/mL) | Standard Deviation 2213.9 |
| Placebo | Plasma Concentration of AT-511 at Specified Timepoints | Day 5, 2 hours | 1934.5 nanograms per milliliter (ng/mL) | Standard Deviation 2210.6 |
| Placebo | Plasma Concentration of AT-511 at Specified Timepoints | Day 5, 4 hours | 202.3 nanograms per milliliter (ng/mL) | Standard Deviation 310.7 |
| Placebo | Plasma Concentration of AT-511 at Specified Timepoints | Day 5, 8 hours | 8.8 nanograms per milliliter (ng/mL) | Standard Deviation 9.5 |
| Placebo | Plasma Concentration of AT-511 at Specified Timepoints | Day 5, 48 hours | 4.6 nanograms per milliliter (ng/mL) | Standard Deviation 40.9 |
Secondary
Plasma Concentration of AT-551 at Specified Timepoints
AT-511 is the free base form of RO7496998 (AT-527). Major metabolites are AT-551, AT-229, and AT-273 (a surrogate for the intracellular concentration of the active triphosphate metabolite AT-9010)
Time frame: Up to 7 days
Population: All participants who received AT-527 and had at least one post-dose drug concentration measurement at a scheduled visit time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentration of AT-551 at Specified Timepoints | Day 1, 0 hour | 1.9 nanograms per milliliter (ng/mL) | Standard Deviation 12.2 |
| Placebo | Plasma Concentration of AT-551 at Specified Timepoints | Day 1, 1 hour | 166.9 nanograms per milliliter (ng/mL) | Standard Deviation 209.8 |
| Placebo | Plasma Concentration of AT-551 at Specified Timepoints | Day 1, 2 hours | 335.7 nanograms per milliliter (ng/mL) | Standard Deviation 257.6 |
| Placebo | Plasma Concentration of AT-551 at Specified Timepoints | Day 1, 4 hours | 195.0 nanograms per milliliter (ng/mL) | Standard Deviation 146.4 |
| Placebo | Plasma Concentration of AT-551 at Specified Timepoints | Day 5, 0 hour | 49.1 nanograms per milliliter (ng/mL) | Standard Deviation 65 |
| Placebo | Plasma Concentration of AT-551 at Specified Timepoints | Day 5, 1 hour | 150.2 nanograms per milliliter (ng/mL) | Standard Deviation 144.5 |
| Placebo | Plasma Concentration of AT-551 at Specified Timepoints | Day 5, 2 hours | 213.6 nanograms per milliliter (ng/mL) | Standard Deviation 201.7 |
| Placebo | Plasma Concentration of AT-551 at Specified Timepoints | Day 5, 4 hours | 138.8 nanograms per milliliter (ng/mL) | Standard Deviation 136.2 |
| Placebo | Plasma Concentration of AT-551 at Specified Timepoints | Day 5, 8 hours | 27.5 nanograms per milliliter (ng/mL) | Standard Deviation 17.5 |
| Placebo | Plasma Concentration of AT-551 at Specified Timepoints | Day 5, 48 hours | 2.6 nanograms per milliliter (ng/mL) | Standard Deviation 5.2 |
Secondary
Time to Alleviation of COVID-19 Symptoms (21.5 Hours)
Time from randomization 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.
Time frame: Up to 29 days
Population: All participants who were randomized to treatment, received a dose of study treatment, and were RT-qPCR positive for SARS-CoV-2 at any point during the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Alleviation of COVID-19 Symptoms (21.5 Hours) | 73.7 hours |
| RO7496998 (AT-527) | Time to Alleviation of COVID-19 Symptoms (21.5 Hours) | 94.5 hours |
Secondary
Time to Alleviation of COVID-19 Symptoms (43 Hours)
Time from randomization 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.
Time frame: Up to 29 days
Population: All participants who were randomized to treatment, received a dose of study treatment, and were RT-qPCR positive for SARS-CoV-2 at any point during the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Alleviation of COVID-19 Symptoms (43 Hours) | 79.6 hours |
| RO7496998 (AT-527) | Time to Alleviation of COVID-19 Symptoms (43 Hours) | 109.5 hours |
Secondary
Time to Alleviation of Individual Symptoms
Time from randomization to the point at which the following criterion is met and maintained (for each individual symptom) for at least 21.5 hours. \- Score of 0 or 1 for Items 1-14 of the COVID-19 Symptom Diary
Time frame: Up to 29 days
Population: All participants who were randomized to treatment, received a dose of study treatment, were RT-qPCR positive for SARS-CoV-2 at any point during the study and had a symptom score of \>= 2 at baseline.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to Alleviation of Individual Symptoms | Nasal Congestion or Runny Nose | 36.4 hours |
| Placebo | Time to Alleviation of Individual Symptoms | Sore Throat | 45.6 hours |
| Placebo | Time to Alleviation of Individual Symptoms | Cough | 37.6 hours |
| Placebo | Time to Alleviation of Individual Symptoms | Shortness of Breath | 24.0 hours |
| Placebo | Time to Alleviation of Individual Symptoms | Muscle or Body Aches | 35.3 hours |
| Placebo | Time to Alleviation of Individual Symptoms | Fatigue | 66.6 hours |
| Placebo | Time to Alleviation of Individual Symptoms | Headache | 23.2 hours |
| Placebo | Time to Alleviation of Individual Symptoms | Chills/Sweats | 36.0 hours |
| Placebo | Time to Alleviation of Individual Symptoms | Feeling Hot or Feverish | 24.6 hours |
| Placebo | Time to Alleviation of Individual Symptoms | Nausea | 31.4 hours |
| Placebo | Time to Alleviation of Individual Symptoms | Vomiting | 20.1 hours |
| Placebo | Time to Alleviation of Individual Symptoms | Diarrhea | 17.6 hours |
| Placebo | Time to Alleviation of Individual Symptoms | Sense of Smell | 132.6 hours |
| Placebo | Time to Alleviation of Individual Symptoms | Sense of Taste | 128.9 hours |
| RO7496998 (AT-527) | Time to Alleviation of Individual Symptoms | Vomiting | 33.0 hours |
| RO7496998 (AT-527) | Time to Alleviation of Individual Symptoms | Nasal Congestion or Runny Nose | 37.3 hours |
| RO7496998 (AT-527) | Time to Alleviation of Individual Symptoms | Chills/Sweats | 39.0 hours |
| RO7496998 (AT-527) | Time to Alleviation of Individual Symptoms | Sore Throat | 33.2 hours |
| RO7496998 (AT-527) | Time to Alleviation of Individual Symptoms | Sense of Smell | 104.9 hours |
| RO7496998 (AT-527) | Time to Alleviation of Individual Symptoms | Cough | 49.5 hours |
| RO7496998 (AT-527) | Time to Alleviation of Individual Symptoms | Feeling Hot or Feverish | 36.2 hours |
| RO7496998 (AT-527) | Time to Alleviation of Individual Symptoms | Shortness of Breath | 47.5 hours |
| RO7496998 (AT-527) | Time to Alleviation of Individual Symptoms | Diarrhea | 66.7 hours |
| RO7496998 (AT-527) | Time to Alleviation of Individual Symptoms | Muscle or Body Aches | 44.9 hours |
| RO7496998 (AT-527) | Time to Alleviation of Individual Symptoms | Nausea | 43.5 hours |
| RO7496998 (AT-527) | Time to Alleviation of Individual Symptoms | Fatigue | 61.3 hours |
| RO7496998 (AT-527) | Time to Alleviation of Individual Symptoms | Sense of Taste | 155.7 hours |
| RO7496998 (AT-527) | Time to Alleviation of Individual Symptoms | Headache | 41.4 hours |
Secondary
Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours)
COVID-19 symptoms will be evaluated using the COVID-19 Symptom Diary (questions 1-12). The severity of each COVID-19 symptom will be recorded on a Likert scale (i.e none/mild/moderate/severe). The time to alleviation or improvement of COVID-19 symptoms is defined as follows: for new symptoms, it is defined as the length of time taken from randomization to the point at which a Score of 0 or 1 has been maintained for a duration of at least 43 hours. For preexisting symptoms, it is defined as the time from randomization to when a patient's symptoms have been maintained or improved (requires at least a single category improvement from baseline on the COVID-19 Symptom Diary Likert scale) for a duration of 43 hours.
Time frame: Up to 29 days
Population: All participants who were randomized to treatment, received a dose of study treatment, and were RT-qPCR positive for SARS-CoV-2 at any point during the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours) | 79.6 hours |
| RO7496998 (AT-527) | Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours) | 109.5 hours |
Secondary
Time to Cessation of SARS-CoV-2 Viral Shedding
Defined as time from randomization to the first time when a negative qualitative virus RNA by RT-PCR test result is obtained.
Time frame: Up to 14 days
Population: All participants who were randomized to treatment, received a dose of study treatment, and were RT-qPCR positive for SARS-CoV-2 at any point during the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Cessation of SARS-CoV-2 Viral Shedding | 13.0 days |
| RO7496998 (AT-527) | Time to Cessation of SARS-CoV-2 Viral Shedding | 13.0 days |
Secondary
Time to One-Category Improvement of Baseline Presenting COVID-19 Symptoms
Time from randomization to the point at which symptoms (Items 1-12 of the COVID-19 Symptom Diary) have improved by at least one category from baseline on the COVID-19 Symptom Diary Likert scale, maintained for at least 21.5 hours.
Time frame: Up to 29 days
Population: All participants who were randomized to treatment, received a dose of study treatment, were RT-qPCR positive for SARS-CoV-2 at any point during the study and with baseline symptoms.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to One-Category Improvement of Baseline Presenting COVID-19 Symptoms | 70.9 hours |
| RO7496998 (AT-527) | Time to One-Category Improvement of Baseline Presenting COVID-19 Symptoms | 81.5 hours |