Trial Outcomes & Findings for Study to Evaluate the Effects of AT-527 in Non-Hospitalized Adult Patients With Mild or Moderate COVID-19 (NCT NCT04709835)

Last Updated: 2022-10-26

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

104 participants

Primary outcome timeframe

Baseline, Day 3, Day 5, Day 7

Results posted on

2022-10-26

Participant Flow

Participants were enrolled in the study at sites in the United Kingdom, Spain, Greece, Latvia, Ireland and Canada.

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.

Participant milestones

Participant milestones
Measure	Pooled Placebo Participants received placebo matched to 550 mg or 1100 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
Overall Study STARTED	40	30	30
Overall Study COMPLETED	40	29	30
Overall Study NOT COMPLETED	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Pooled Placebo Participants received placebo matched to 550 mg or 1100 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
Overall Study Withdrawal by Subject	0	1	0

Baseline Characteristics

Study to Evaluate the Effects of AT-527 in Non-Hospitalized Adult Patients With Mild or Moderate COVID-19

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pooled Placebo n=40 Participants Participants received placebo matched to 550 mg or 1100 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) n=30 Participants Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) n=30 Participants Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.	Total n=100 Participants Total of all reporting groups
Age, Continuous	36.8 years STANDARD_DEVIATION 13.2 • n=5 Participants	32.7 years STANDARD_DEVIATION 10.9 • n=7 Participants	40.3 years STANDARD_DEVIATION 15.6 • n=5 Participants	36.6 years STANDARD_DEVIATION 13.6 • n=4 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	15 Participants n=7 Participants	17 Participants n=5 Participants	54 Participants n=4 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	15 Participants n=7 Participants	13 Participants n=5 Participants	46 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	36 Participants n=5 Participants	26 Participants n=7 Participants	29 Participants n=5 Participants	91 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) White	38 Participants n=5 Participants	29 Participants n=7 Participants	28 Participants n=5 Participants	95 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA at Baseline	6.24 log10 copies/mL STANDARD_DEVIATION 1.40 • n=5 Participants	6.98 log10 copies/mL STANDARD_DEVIATION 1.10 • n=7 Participants	5.94 log10 copies/mL STANDARD_DEVIATION 1.46 • n=5 Participants	6.37 log10 copies/mL STANDARD_DEVIATION 1.39 • n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo Matched to AT-527 550 mg n=30 Participants Participants received placebo matched to 550 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) n=30 Participants Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
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	-1.26 log10 copies/mL Standard Error 0.206	—
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 0.230	-2.11 log10 copies/mL Standard Error 0.226	—
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 0.220	-3.38 log10 copies/mL Standard Error 0.220	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo Matched to AT-527 550 mg n=40 Participants Participants received placebo matched to 550 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) n=30 Participants Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
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 0.190	-1.18 log10 copies/mL Standard Error 0.223	—
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	-2.31 log10 copies/mL Standard Error 0.231	—
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	-2.78 log10 copies/mL Standard Error 0.236	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo Matched to AT-527 550 mg n=40 Participants Participants received placebo matched to 550 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) n=30 Participants Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) n=30 Participants Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
Time to Cessation of SARS-CoV-2 Viral Shedding	NA hours Interval 144.2 to NA = Not estimable due to low number of participants with event.	NA hours Interval 143.8 to NA = Not estimable due to low number of participants with event.	NA hours Interval 141.1 to NA = Not estimable due to low number of participants with event.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo Matched to AT-527 550 mg n=40 Participants Participants received placebo matched to 550 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) n=30 Participants Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) n=30 Participants Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
Time to Sustained Non-Detectable SARS-CoV-2 Virus RNA	NA hours NA = Not estimable due to low number of participants with event.	NA hours NA = Not estimable due to low number of participants with event.	NA hours NA = Not estimable due to low number of participants with event.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo Matched to AT-527 550 mg n=40 Participants Participants received placebo matched to 550 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) n=30 Participants Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) n=30 Participants Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints Baseline	100 percentage of participants	100 percentage of participants	96.7 percentage of participants
Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints Day 3	95.0 percentage of participants	100 percentage of participants	93.1 percentage of participants
Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints Day 5	84.2 percentage of participants	90.0 percentage of participants	83.3 percentage of participants
Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints Day 7	76.9 percentage of participants	79.3 percentage of participants	76.7 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo Matched to AT-527 550 mg n=40 Participants Participants received placebo matched to 550 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) n=30 Participants Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) n=30 Participants Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA	651.56 log10 copies/mL*hour Standard Deviation 189.10	733.70 log10 copies/mL*hour Standard Deviation 146.63	618.62 log10 copies/mL*hour Standard Deviation 194.88

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo Matched to AT-527 550 mg n=40 Participants Participants received placebo matched to 550 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) n=30 Participants Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) n=30 Participants Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 Hours)	43.4 hours Interval 9.3 to 104.7	57.2 hours Interval 9.0 to 115.8	56.4 hours Interval 2.5 to 96.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo Matched to AT-527 550 mg n=40 Participants Participants received placebo matched to 550 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) n=30 Participants Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) n=30 Participants Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
Time to Alleviation or Improvement of COVID-19 Symptoms (43 Hours)	43.4 hours Interval 9.3 to 104.7	57.2 hours Interval 9.0 to 141.2	58.1 hours Interval 2.5 to 118.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo Matched to AT-527 550 mg n=40 Participants Participants received placebo matched to 550 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) n=30 Participants Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) n=30 Participants Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
Time to Alleviation of COVID-19 Symptoms (21.5 Hours)	43.4 hours Interval 9.3 to 104.7	57.2 hours Interval 9.0 to 115.8	56.4 hours Interval 8.2 to 96.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo Matched to AT-527 550 mg n=40 Participants Participants received placebo matched to 550 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) n=30 Participants Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) n=30 Participants Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
Time to Alleviation of COVID-19 Symptoms (43 Hours)	43.4 hours Interval 9.3 to 104.7	57.2 hours Interval 9.0 to 141.2	58.1 hours Interval 8.2 to 118.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo Matched to AT-527 550 mg n=2 Participants Participants received placebo matched to 550 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
Duration of Fever	10.6 hours Interval 9.6 to 11.7	—	—

SECONDARY outcome

Timeframe: Up to 33 Days

COVID-19 related complications include death, hospitalization, radiologically confirmed pneumonia, acute respiratory failure, sepsis, coagulopathy, pericarditis, myocarditis, and cardiac failure.

Outcome measures

Outcome measures
Measure	Placebo Matched to AT-527 550 mg n=40 Participants Participants received placebo matched to 550 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) n=30 Participants Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) n=30 Participants Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
Percentage of Participants With COVID-19 Related Complications	0 percentage of participants	3.3 percentage of participants	3.3 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo Matched to AT-527 550 mg n=40 Participants Participants received placebo matched to 550 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) n=30 Participants Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) n=30 Participants Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
Time to Alleviation of an Individual Symptom Sore Throat	20.5 hours Interval 14.1 to 22.7	24.1 hours Interval 9.8 to 45.0	111.7 hours Interval 22.1 to 201.4
Time to Alleviation of an Individual Symptom Cough	22.6 hours Interval 11.8 to 129.3	90.7 hours Interval 23.7 to 140.4	33.9 hours Interval 20.5 to 119.2
Time to Alleviation of an Individual Symptom Aches and Pains	33.1 hours Interval 11.8 to 60.4	22.3 hours Interval 16.3 to 62.2	94.4 hours Interval 48.1 to 177.7
Time to Alleviation of an Individual Symptom Feeling Hot or Feverish	26.5 hours Interval 11.8 to 35.7	48.0 hours Interval 24.0 to 72.0	40.3 hours Interval 15.9 to 63.4
Time to Alleviation of an Individual Symptom Diarrhea	NA hours NA: not estimable due to low number of participants with an event.	—	9.8 hours Interval 9.8 to 9.8
Time to Alleviation of an Individual Symptom Nasal Congestion/Runny Nose	27.6 hours Interval 11.3 to 59.9	34.2 hours Interval 15.8 to 82.4	32.7 hours Interval 10.0 to 57.7
Time to Alleviation of an Individual Symptom Shortness of Breath	23.9 hours Interval 11.5 to NA: not estimable due to low number of participants with an event.	68.9 hours Interval 68.5 to 69.2	11.6 hours Interval 11.6 to 11.6
Time to Alleviation of an Individual Symptom Fatigue	47.8 hours Interval 22.6 to 178.1	44.4 hours Interval 10.5 to 94.5	70.6 hours Interval 22.6 to 106.0
Time to Alleviation of an Individual Symptom Headache	32.0 hours Interval 10.1 to 95.8	11.7 hours Interval 9.8 to 93.6	34.4 hours Interval 21.8 to 105.4
Time to Alleviation of an Individual Symptom Chills/Sweats	11.8 hours Interval 9.8 to 24.1	12.0 hours Interval 9.0 to 35.8	25.0 hours Interval 17.1 to 41.4
Time to Alleviation of an Individual Symptom Nausea	NA hours Interval 21.1 to NA: not estimable due to low number of participants with an event.	—	—
Time to Alleviation of an Individual Symptom Vomiting	NA hours Interval 11.0 to NA: not estimable due to low number of participants with an event.	—	—
Time to Alleviation of an Individual Symptom Sense of Smell	261.5 hours Interval 164.9 to NA: not estimable due to low number of participants with an event.	290.2 hours Interval 130.7 to NA: not estimable due to low number of participants with an event.	213.1 hours Interval 129.7 to 513.7
Time to Alleviation of an Individual Symptom Sense of Taste	221.1 hours Interval 165.3 to 297.6	214.1 hours Interval 94.1 to NA: not estimable due to low number of participants with an event.	178.5 hours Interval 105.5 to 391.2

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo Matched to AT-527 550 mg n=40 Participants Participants received placebo matched to 550 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) n=30 Participants Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) n=30 Participants Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
Percentage of Participants With Adverse Events (AEs)	27.5 percentage of participants	20.0 percentage of participants	33.3 percentage of participants

SECONDARY outcome

Timeframe: 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.

AT-511 is the free base form of AT-527. Its major metabolites are AT-551, AT-229, and AT-273.

Outcome measures

Outcome measures
Measure	Placebo Matched to AT-527 550 mg n=30 Participants Participants received placebo matched to 550 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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 2365.0	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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 0.0	—	—
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 0.0	—	—
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	—	—
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	—	—
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	—	—
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 0.0	—	—
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 145.0	—	—
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	—	—
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	—	—
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 0.0	—	—
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 29.0	—	—
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	—	—
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	—	—
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 53.0	—	—
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	—	—
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	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo Matched to AT-527 550 mg n=30 Participants Participants received placebo matched to 550 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
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	—	—
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	—	—
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	—	—
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 0.0	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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 0.0	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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 0.0	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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 0.0	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—

Adverse Events

Pooled Placebo

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

AT-527 550 mg (1x550 mg)

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

AT-527 1100 mg (4x275 mg)

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pooled Placebo n=40 participants at risk Participants received placebo matched to 550 mg or 1100 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) n=30 participants at risk Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) n=30 participants at risk Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
Cardiac disorders Atrial flutter	2.5% 1/40 • Number of events 1 • Up to 33 days 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.	0.00% 0/30 • Up to 33 days 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.	0.00% 0/30 • Up to 33 days 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.
Infections and infestations COVID-19 pneumonia	0.00% 0/40 • Up to 33 days 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.	3.3% 1/30 • Number of events 1 • Up to 33 days 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.	3.3% 1/30 • Number of events 1 • Up to 33 days 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.

Other adverse events

Other adverse events
Measure	Pooled Placebo n=40 participants at risk Participants received placebo matched to 550 mg or 1100 mg AT-527 twice a day (BID) on Days 1-5.	AT-527 550 mg (1x550 mg) n=30 participants at risk Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.	AT-527 1100 mg (4x275 mg) n=30 participants at risk Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
Gastrointestinal disorders Nausea	2.5% 1/40 • Number of events 1 • Up to 33 days 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.	3.3% 1/30 • Number of events 1 • Up to 33 days 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.	10.0% 3/30 • Number of events 3 • Up to 33 days 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.
Gastrointestinal disorders Vomiting	2.5% 1/40 • Number of events 1 • Up to 33 days 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.	0.00% 0/30 • Up to 33 days 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.	16.7% 5/30 • Number of events 5 • Up to 33 days 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.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

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