Trial Outcomes & Findings for Study to Evaluate the Effects of RO7496998 (AT-527) in Non-Hospitalized Adult and Adolescent Participants With Mild or Moderate COVID-19 (NCT NCT04889040)
NCT ID: NCT04889040
Last Updated: 2024-01-05
Results Overview
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.
TERMINATED
PHASE3
216 participants
Up to 29 days
2024-01-05
Participant Flow
Participants were non-hospitalized, with mild to moderate COVID-19, with or without risk factors for severe disease.
Participant milestones
| Measure |
Placebo
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Overall Study
STARTED
|
73
|
143
|
|
Overall Study
Received Treatment
|
71
|
141
|
|
Overall Study
COMPLETED
|
68
|
138
|
|
Overall Study
NOT COMPLETED
|
5
|
5
|
Reasons for withdrawal
| Measure |
Placebo
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
3
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Adverse Event
|
2
|
1
|
Baseline Characteristics
All participants who were randomized to treatment, received a dose of study treatment, were reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) positive for SARS-CoV-2 at any point during the study and did not have missing data.
Baseline characteristics by cohort
| Measure |
Placebo
n=73 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
n=143 Participants
Orally administered, 550 mg twice daily (BID) for 5 days
|
Total
n=216 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
41.7 years
STANDARD_DEVIATION 14.9 • n=73 Participants
|
41.1 years
STANDARD_DEVIATION 13.2 • n=143 Participants
|
41.3 years
STANDARD_DEVIATION 13.7 • n=216 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=73 Participants
|
62 Participants
n=143 Participants
|
94 Participants
n=216 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=73 Participants
|
81 Participants
n=143 Participants
|
122 Participants
n=216 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
6 Participants
n=73 Participants
|
9 Participants
n=143 Participants
|
15 Participants
n=216 Participants
|
|
Race (NIH/OMB)
Asian
|
14 Participants
n=73 Participants
|
26 Participants
n=143 Participants
|
40 Participants
n=216 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=73 Participants
|
0 Participants
n=143 Participants
|
1 Participants
n=216 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=73 Participants
|
3 Participants
n=143 Participants
|
4 Participants
n=216 Participants
|
|
Race (NIH/OMB)
White
|
50 Participants
n=73 Participants
|
105 Participants
n=143 Participants
|
155 Participants
n=216 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=73 Participants
|
0 Participants
n=143 Participants
|
0 Participants
n=216 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=73 Participants
|
0 Participants
n=143 Participants
|
1 Participants
n=216 Participants
|
|
Number of COVID-19 Symptoms Present at Baseline
|
7.85 Number of Covid-19 Symptoms
STANDARD_DEVIATION 2.58 • n=68 Participants • All participants who were randomized to treatment, received a dose of study treatment, were reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) positive for SARS-CoV-2 at any point during the study and did not have missing data.
|
7.92 Number of Covid-19 Symptoms
STANDARD_DEVIATION 2.74 • n=130 Participants • All participants who were randomized to treatment, received a dose of study treatment, were reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) positive for SARS-CoV-2 at any point during the study and did not have missing data.
|
7.90 Number of Covid-19 Symptoms
STANDARD_DEVIATION 2.68 • n=198 Participants • All participants who were randomized to treatment, received a dose of study treatment, were reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) positive for SARS-CoV-2 at any point during the study and did not have missing data.
|
PRIMARY outcome
Timeframe: Up to 29 daysPopulation: 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.
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.
Outcome measures
| Measure |
Placebo
n=70 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
n=137 Participants
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours)
|
73.7 hours
Interval 47.1 to 105.8
|
94.5 hours
Interval 68.1 to 131.7
|
SECONDARY outcome
Timeframe: Up to 29 daysPopulation: 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.
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.
Outcome measures
| Measure |
Placebo
n=70 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
n=137 Participants
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours)
|
79.6 hours
Interval 55.7 to 108.2
|
109.5 hours
Interval 83.8 to 147.5
|
SECONDARY outcome
Timeframe: Up to 29 daysPopulation: 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.
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.
Outcome measures
| Measure |
Placebo
n=70 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
n=137 Participants
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Time to Alleviation of COVID-19 Symptoms (21.5 Hours)
|
73.7 hours
Interval 47.1 to 105.8
|
94.5 hours
Interval 68.1 to 131.7
|
SECONDARY outcome
Timeframe: Up to 29 daysPopulation: 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.
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.
Outcome measures
| Measure |
Placebo
n=70 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
n=137 Participants
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Time to Alleviation of COVID-19 Symptoms (43 Hours)
|
79.6 hours
Interval 55.7 to 108.2
|
109.5 hours
Interval 83.8 to 147.5
|
SECONDARY outcome
Timeframe: Up to 29 daysPopulation: 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.
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.
Outcome measures
| Measure |
Placebo
n=68 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
n=130 Participants
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Time to One-Category Improvement of Baseline Presenting COVID-19 Symptoms
|
70.9 hours
Interval 41.8 to 91.8
|
81.5 hours
Interval 60.5 to 119.9
|
SECONDARY outcome
Timeframe: Up to 29 daysPopulation: 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.
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
Outcome measures
| Measure |
Placebo
n=70 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
n=137 Participants
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Time to Alleviation of Individual Symptoms
Nasal Congestion or Runny Nose
|
36.4 hours
Interval 23.4 to 60.6
|
37.3 hours
Interval 23.4 to 57.6
|
|
Time to Alleviation of Individual Symptoms
Sore Throat
|
45.6 hours
Interval 23.4 to 75.1
|
33.2 hours
Interval 20.9 to 54.3
|
|
Time to Alleviation of Individual Symptoms
Cough
|
37.6 hours
Interval 26.8 to 118.7
|
49.5 hours
Interval 28.4 to 106.4
|
|
Time to Alleviation of Individual Symptoms
Shortness of Breath
|
24.0 hours
Interval 11.8 to 106.8
|
47.5 hours
Interval 32.4 to 96.8
|
|
Time to Alleviation of Individual Symptoms
Muscle or Body Aches
|
35.3 hours
Interval 14.3 to 59.4
|
44.9 hours
Interval 33.1 to 53.0
|
|
Time to Alleviation of Individual Symptoms
Fatigue
|
66.6 hours
Interval 36.5 to 118.9
|
61.3 hours
Interval 47.1 to 108.1
|
|
Time to Alleviation of Individual Symptoms
Headache
|
23.2 hours
Interval 14.5 to 41.8
|
41.4 hours
Interval 24.4 to 59.5
|
|
Time to Alleviation of Individual Symptoms
Chills/Sweats
|
36.0 hours
Interval 22.5 to 57.6
|
39.0 hours
Interval 28.4 to 50.5
|
|
Time to Alleviation of Individual Symptoms
Feeling Hot or Feverish
|
24.6 hours
Interval 16.4 to 66.7
|
36.2 hours
Interval 19.7 to 61.4
|
|
Time to Alleviation of Individual Symptoms
Nausea
|
31.4 hours
Interval 11.1 to
Not evaluable due to an insufficient number of events
|
43.5 hours
Interval 22.6 to 73.4
|
|
Time to Alleviation of Individual Symptoms
Vomiting
|
20.1 hours
Interval 16.4 to
Not evaluable due to an insufficient number of events
|
33.0 hours
Not evaluable due to an insufficient number of events
|
|
Time to Alleviation of Individual Symptoms
Diarrhea
|
17.6 hours
Interval 14.9 to 73.6
|
66.7 hours
Interval 19.8 to 107.2
|
|
Time to Alleviation of Individual Symptoms
Sense of Smell
|
132.6 hours
Interval 84.3 to 229.0
|
104.9 hours
Interval 72.6 to 206.0
|
|
Time to Alleviation of Individual Symptoms
Sense of Taste
|
128.9 hours
Interval 84.3 to 202.2
|
155.7 hours
Interval 52.5 to 371.7
|
SECONDARY outcome
Timeframe: Up to Day 33 visitPopulation: 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.
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.
Outcome measures
| Measure |
Placebo
n=70 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
n=137 Participants
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Percentage of Participants Requiring Hospitalization for COVID-19
|
10.0 percentage of participants
Interval 1.25 to 18.75
|
2.9 percentage of participants
Interval 0.0 to 6.51
|
SECONDARY outcome
Timeframe: Up to Day 33 visitPopulation: 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.
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.
Outcome measures
| Measure |
Placebo
n=70 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
n=137 Participants
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Percentage of Participants With Greater Than or Equal to 1 COVID-19 Related Medically Attended Visit
|
14.3 percentage of participants
Interval 4.2 to 24.37
|
10.2 percentage of participants
Interval 4.05 to 16.38
|
SECONDARY outcome
Timeframe: Up to 29 daysPopulation: 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.
Time to return to an afebrile state (temperature ≤ 37.5°C) maintained for at least 21.5 hours.
Outcome measures
| Measure |
Placebo
n=12 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
n=20 Participants
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Duration of Fever
|
47.3 hours
Interval 12.6 to 82.2
|
55.7 hours
Interval 25.9 to 96.4
|
SECONDARY outcome
Timeframe: Up to Day 33 visitPopulation: 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.
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.
Outcome measures
| Measure |
Placebo
n=70 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
n=137 Participants
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Percentage of Participants With COVID-19 Related Complications
|
10.0 percentage of participants
Interval 1.25 to 18.75
|
4.4 percentage of participants
Interval 0.1 to 8.66
|
SECONDARY outcome
Timeframe: Up to Day 33 visitPopulation: 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.
Post-treatment infections were defined as any treatment-emergent adverse event with a primary system organ class of infections and infestations.
Outcome measures
| Measure |
Placebo
n=70 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
n=137 Participants
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Percentage of Participants With Any Post-Treatment Infection
|
14.3 percentage of participants
Interval 4.2 to 24.37
|
9.5 percentage of participants
Interval 3.51 to 15.47
|
SECONDARY outcome
Timeframe: Baseline and on Days 3, 5, 7 and 14Population: 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.
SARS-CoV-2 virus RNA will be measured by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR)
Outcome measures
| Measure |
Placebo
n=70 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
n=137 Participants
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
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
|
6.59 log10 copies/mL
Standard Deviation 1.54
|
|
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
|
-1.07 log10 copies/mL
Standard Deviation 1.16
|
|
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 1.40
|
-2.01 log10 copies/mL
Standard Deviation 1.50
|
|
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
|
-2.98 log10 copies/mL
Standard Deviation 1.66
|
|
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
|
-4.25 log10 copies/mL
Standard Deviation 1.64
|
SECONDARY outcome
Timeframe: Up to 14 daysPopulation: 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.
Defined as time from randomization to the first time when a negative qualitative virus RNA by RT-PCR test result is obtained.
Outcome measures
| Measure |
Placebo
n=70 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
n=137 Participants
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Time to Cessation of SARS-CoV-2 Viral Shedding
|
13.0 days
Interval 12.8 to
Not evaluable due to an insufficient number of events
|
13.0 days
Interval 13.0 to 13.1
|
SECONDARY outcome
Timeframe: Baseline and on Days 3, 5, 7 and 14Population: 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.
Defined as percentage of participants with a positive qualitative virus RNA by RT-PCR.
Outcome measures
| Measure |
Placebo
n=70 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
n=137 Participants
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints
Baseline
|
97.1 percentage of participants
|
100 percentage of participants
|
|
Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints
Day 3
|
98.5 percentage of participants
|
96.4 percentage of participants
|
|
Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints
Day 5
|
89.7 percentage of participants
|
91.9 percentage of participants
|
|
Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints
Day 7
|
74.6 percentage of participants
|
76.3 percentage of participants
|
|
Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints
Day 14
|
43.9 percentage of participants
|
34.4 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1 prior to dosing, Day 3, Day 5, Day 7 and Day 14Population: 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.
Outcome measures
| Measure |
Placebo
n=69 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
n=137 Participants
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA
|
1122.39 log10 copies/mL*hour
Standard Deviation 339.70
|
1174.30 log10 copies/mL*hour
Standard Deviation 377.49
|
SECONDARY outcome
Timeframe: Up to Day 33 visitPopulation: All participants who received at least one dose of study treatment
Outcome measures
| Measure |
Placebo
n=71 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
n=141 Participants
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Percentage of Participants With Adverse Events (AEs)
|
36.6 percentage of participants
|
39.0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 7 daysPopulation: All participants who received AT-527 and had at least one post-dose drug concentration measurement at a scheduled visit time point
AT-511 is the free base form of RO7496998 (AT-527).
Outcome measures
| Measure |
Placebo
n=137 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Plasma Concentration of AT-511 at Specified Timepoints
Day 5, 48 hours
|
4.6 nanograms per milliliter (ng/mL)
Standard Deviation 40.9
|
—
|
|
Plasma Concentration of AT-511 at Specified Timepoints
Day 1, 0 hour
|
17.4 nanograms per milliliter (ng/mL)
Standard Deviation 158.6
|
—
|
|
Plasma Concentration of AT-511 at Specified Timepoints
Day 1, 1 hour
|
1456.8 nanograms per milliliter (ng/mL)
Standard Deviation 1757.7
|
—
|
|
Plasma Concentration of AT-511 at Specified Timepoints
Day 1, 2 hours
|
1029.3 nanograms per milliliter (ng/mL)
Standard Deviation 1085.5
|
—
|
|
Plasma Concentration of AT-511 at Specified Timepoints
Day 1, 4 hours
|
206.3 nanograms per milliliter (ng/mL)
Standard Deviation 289.5
|
—
|
|
Plasma Concentration of AT-511 at Specified Timepoints
Day 5, 0 hour
|
52.8 nanograms per milliliter (ng/mL)
Standard Deviation 271.0
|
—
|
|
Plasma Concentration of AT-511 at Specified Timepoints
Day 5, 1 hour
|
1659.0 nanograms per milliliter (ng/mL)
Standard Deviation 2213.9
|
—
|
|
Plasma Concentration of AT-511 at Specified Timepoints
Day 5, 2 hours
|
1934.5 nanograms per milliliter (ng/mL)
Standard Deviation 2210.6
|
—
|
|
Plasma Concentration of AT-511 at Specified Timepoints
Day 5, 4 hours
|
202.3 nanograms per milliliter (ng/mL)
Standard Deviation 310.7
|
—
|
|
Plasma Concentration of AT-511 at Specified Timepoints
Day 5, 8 hours
|
8.8 nanograms per milliliter (ng/mL)
Standard Deviation 9.5
|
—
|
SECONDARY outcome
Timeframe: Up to 7 daysPopulation: All participants who received AT-527 and had at least one post-dose drug concentration measurement at a scheduled visit time point
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)
Outcome measures
| Measure |
Placebo
n=137 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Plasma Concentration of AT-551 at Specified Timepoints
Day 1, 0 hour
|
1.9 nanograms per milliliter (ng/mL)
Standard Deviation 12.2
|
—
|
|
Plasma Concentration of AT-551 at Specified Timepoints
Day 1, 1 hour
|
166.9 nanograms per milliliter (ng/mL)
Standard Deviation 209.8
|
—
|
|
Plasma Concentration of AT-551 at Specified Timepoints
Day 1, 2 hours
|
335.7 nanograms per milliliter (ng/mL)
Standard Deviation 257.6
|
—
|
|
Plasma Concentration of AT-551 at Specified Timepoints
Day 1, 4 hours
|
195.0 nanograms per milliliter (ng/mL)
Standard Deviation 146.4
|
—
|
|
Plasma Concentration of AT-551 at Specified Timepoints
Day 5, 0 hour
|
49.1 nanograms per milliliter (ng/mL)
Standard Deviation 65.0
|
—
|
|
Plasma Concentration of AT-551 at Specified Timepoints
Day 5, 1 hour
|
150.2 nanograms per milliliter (ng/mL)
Standard Deviation 144.5
|
—
|
|
Plasma Concentration of AT-551 at Specified Timepoints
Day 5, 2 hours
|
213.6 nanograms per milliliter (ng/mL)
Standard Deviation 201.7
|
—
|
|
Plasma Concentration of AT-551 at Specified Timepoints
Day 5, 4 hours
|
138.8 nanograms per milliliter (ng/mL)
Standard Deviation 136.2
|
—
|
|
Plasma Concentration of AT-551 at Specified Timepoints
Day 5, 8 hours
|
27.5 nanograms per milliliter (ng/mL)
Standard Deviation 17.5
|
—
|
|
Plasma Concentration of AT-551 at Specified Timepoints
Day 5, 48 hours
|
2.6 nanograms per milliliter (ng/mL)
Standard Deviation 5.2
|
—
|
SECONDARY outcome
Timeframe: Up to 7 daysPopulation: All participants who received AT-527 and had at least one post-dose drug concentration measurement at a scheduled visit time point
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)
Outcome measures
| Measure |
Placebo
n=137 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Plasma Concentration of AT-229 at Specified Timepoints
Day 1, 0 hour
|
2.2 nanograms per milliliter (ng/mL)
Standard Deviation 18.4
|
—
|
|
Plasma Concentration of AT-229 at Specified Timepoints
Day 1, 1 hour
|
123.6 nanograms per milliliter (ng/mL)
Standard Deviation 172.5
|
—
|
|
Plasma Concentration of AT-229 at Specified Timepoints
Day 1, 2 hours
|
507.8 nanograms per milliliter (ng/mL)
Standard Deviation 497.5
|
—
|
|
Plasma Concentration of AT-229 at Specified Timepoints
Day 1, 4 hours
|
354.4 nanograms per milliliter (ng/mL)
Standard Deviation 259.2
|
—
|
|
Plasma Concentration of AT-229 at Specified Timepoints
Day 5, 0 hour
|
367.8 nanograms per milliliter (ng/mL)
Standard Deviation 259.1
|
—
|
|
Plasma Concentration of AT-229 at Specified Timepoints
Day 5, 1 hour
|
418.0 nanograms per milliliter (ng/mL)
Standard Deviation 257.6
|
—
|
|
Plasma Concentration of AT-229 at Specified Timepoints
Day 5, 2 hours
|
454.3 nanograms per milliliter (ng/mL)
Standard Deviation 331.7
|
—
|
|
Plasma Concentration of AT-229 at Specified Timepoints
Day 5, 4 hours
|
490.1 nanograms per milliliter (ng/mL)
Standard Deviation 296.4
|
—
|
|
Plasma Concentration of AT-229 at Specified Timepoints
Day 5, 8 hours
|
279.6 nanograms per milliliter (ng/mL)
Standard Deviation 176.0
|
—
|
|
Plasma Concentration of AT-229 at Specified Timepoints
Day 5, 48 hours
|
118.7 nanograms per milliliter (ng/mL)
Standard Deviation 127.2
|
—
|
SECONDARY outcome
Timeframe: Up to 7 daysPopulation: All participants who received AT-527 and had at least one post-dose drug concentration measurement at a scheduled visit time point
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)
Outcome measures
| Measure |
Placebo
n=137 Participants
The dose and regimen of the placebo will match that of AT-527.
|
RO7496998 (AT-527)
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Plasma Concentration of AT-273 at Specified Timepoints
Day 1, 0 hour
|
0.7 nanograms per milliliter (ng/mL)
Standard Deviation 2.5
|
—
|
|
Plasma Concentration of AT-273 at Specified Timepoints
Day 1, 1 hour
|
15.5 nanograms per milliliter (ng/mL)
Standard Deviation 26.9
|
—
|
|
Plasma Concentration of AT-273 at Specified Timepoints
Day 1, 2 hours
|
135.1 nanograms per milliliter (ng/mL)
Standard Deviation 136.2
|
—
|
|
Plasma Concentration of AT-273 at Specified Timepoints
Day 1, 4 hours
|
173.5 nanograms per milliliter (ng/mL)
Standard Deviation 120.6
|
—
|
|
Plasma Concentration of AT-273 at Specified Timepoints
Day 5, 0 hour
|
149.8 nanograms per milliliter (ng/mL)
Standard Deviation 78.1
|
—
|
|
Plasma Concentration of AT-273 at Specified Timepoints
Day 5, 1 hour
|
141.7 nanograms per milliliter (ng/mL)
Standard Deviation 72.7
|
—
|
|
Plasma Concentration of AT-273 at Specified Timepoints
Day 5, 2 hours
|
108.8 nanograms per milliliter (ng/mL)
Standard Deviation 61.0
|
—
|
|
Plasma Concentration of AT-273 at Specified Timepoints
Day 5, 4 hours
|
172.7 nanograms per milliliter (ng/mL)
Standard Deviation 129.2
|
—
|
|
Plasma Concentration of AT-273 at Specified Timepoints
Day 5, 8 hours
|
118.6 nanograms per milliliter (ng/mL)
Standard Deviation 80.2
|
—
|
|
Plasma Concentration of AT-273 at Specified Timepoints
Day 5, 48 hours
|
48.4 nanograms per milliliter (ng/mL)
Standard Deviation 32.7
|
—
|
Adverse Events
Placebo
AT-527
Serious adverse events
| Measure |
Placebo
n=71 participants at risk
The dose and regimen of the placebo will match that of AT-527.
|
AT-527
n=141 participants at risk
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Infections and infestations
COVID-19
|
4.2%
3/71 • Number of events 3 • up to the Day 33 visit
Safety analyses were performed on the safety evaluable set, which consisted of all randomized participants who received at least one dose of study treatment.
|
1.4%
2/141 • Number of events 2 • up to the Day 33 visit
Safety analyses were performed on the safety evaluable set, which consisted of all randomized participants who received at least one dose of study treatment.
|
|
Infections and infestations
COVID-19 pneumonia
|
5.6%
4/71 • Number of events 4 • up to the Day 33 visit
Safety analyses were performed on the safety evaluable set, which consisted of all randomized participants who received at least one dose of study treatment.
|
0.71%
1/141 • Number of events 1 • up to the Day 33 visit
Safety analyses were performed on the safety evaluable set, which consisted of all randomized participants who received at least one dose of study treatment.
|
|
Infections and infestations
Pneumonia staphylococcal
|
0.00%
0/71 • up to the Day 33 visit
Safety analyses were performed on the safety evaluable set, which consisted of all randomized participants who received at least one dose of study treatment.
|
0.71%
1/141 • Number of events 1 • up to the Day 33 visit
Safety analyses were performed on the safety evaluable set, which consisted of all randomized participants who received at least one dose of study treatment.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/71 • up to the Day 33 visit
Safety analyses were performed on the safety evaluable set, which consisted of all randomized participants who received at least one dose of study treatment.
|
0.71%
1/141 • Number of events 1 • up to the Day 33 visit
Safety analyses were performed on the safety evaluable set, which consisted of all randomized participants who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/71 • up to the Day 33 visit
Safety analyses were performed on the safety evaluable set, which consisted of all randomized participants who received at least one dose of study treatment.
|
0.71%
1/141 • Number of events 1 • up to the Day 33 visit
Safety analyses were performed on the safety evaluable set, which consisted of all randomized participants who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/71 • up to the Day 33 visit
Safety analyses were performed on the safety evaluable set, which consisted of all randomized participants who received at least one dose of study treatment.
|
0.71%
1/141 • Number of events 1 • up to the Day 33 visit
Safety analyses were performed on the safety evaluable set, which consisted of all randomized participants who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/71 • up to the Day 33 visit
Safety analyses were performed on the safety evaluable set, which consisted of all randomized participants who received at least one dose of study treatment.
|
0.71%
1/141 • Number of events 1 • up to the Day 33 visit
Safety analyses were performed on the safety evaluable set, which consisted of all randomized participants who received at least one dose of study treatment.
|
Other adverse events
| Measure |
Placebo
n=71 participants at risk
The dose and regimen of the placebo will match that of AT-527.
|
AT-527
n=141 participants at risk
Orally administered, 550 mg twice daily (BID) for 5 days
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/71 • up to the Day 33 visit
Safety analyses were performed on the safety evaluable set, which consisted of all randomized participants who received at least one dose of study treatment.
|
5.7%
8/141 • Number of events 8 • up to the Day 33 visit
Safety analyses were performed on the safety evaluable set, which consisted of all randomized participants who received at least one dose of study treatment.
|
|
Nervous system disorders
Headache
|
7.0%
5/71 • Number of events 5 • up to the Day 33 visit
Safety analyses were performed on the safety evaluable set, which consisted of all randomized participants who received at least one dose of study treatment.
|
2.8%
4/141 • Number of events 4 • up to the Day 33 visit
Safety analyses were performed on the safety evaluable set, which consisted of all randomized participants who received at least one dose of study treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER