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    Clinical Trial Results:
    A Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Antiviral Activity, Safety, Pharmacokinetics, and Efficacy of RO7496998 (AT-527) in Non-Hospitalized Adult Patients with Mild or Moderate COVID-19

    Summary
    EudraCT number
    		 2020-005366-34
    Trial protocol
    		 IE   BG   ES   LV   GR   LT  
    Global end of trial date
    13 Oct 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    04 Oct 2022
    First version publication date
    04 Oct 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    WV43042
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04709835
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    13 Oct 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Oct 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this Phase II, randomized, double-blind, placebo-controlled study was to evaluate the antiviral activity of selected dose regimens of AT-527 compared with placebo in non-hospitalized adult participants with mild or moderate COVID-19.
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    03 Feb 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 1
    Country: Number of subjects enrolled
    Spain: 15
    Country: Number of subjects enrolled
    United Kingdom: 76
    Country: Number of subjects enrolled
    Greece: 4
    Country: Number of subjects enrolled
    Ireland: 1
    Country: Number of subjects enrolled
    Latvia: 3
    Worldwide total number of subjects
    100
    EEA total number of subjects
    23
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    97
    From 65 to 84 years
    3
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study enrolled 104 participants at sites in the United Kingdom, Spain, Greece, Latvia, Ireland and Canada.

    Pre-assignment
    Screening details
    		 The study enrolled 104 non-hospitalized adult participants with mild or moderate COVID-19. Four enrolled participants were not treated and are not included in the Results.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Pooled Placebo
    Arm description
    		 Participants received placebo matched to 550 mg or 1100 mg AT-527 twice a day (BID) on Days 1-5.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The dose and regimen of the placebo matched that of the respective AT-527 comparator arm.

    Arm title
    		 AT-527 550 mg (1x550 mg)
    Arm description
    		 Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.
    Arm type
    		 Experimental

    Investigational medicinal product name
    AT-527
    Investigational medicinal product code
    Other name
    RO7496998
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.

    Arm title
    		 AT-527 1100 mg (4x275 mg)
    Arm description
    		 Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.
    Arm type
    		 Experimental

    Investigational medicinal product name
    AT-527
    Investigational medicinal product code
    Other name
    RO7496998
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.

    Number of subjects in period 1
    		Pooled Placebo AT-527 550 mg (1x550 mg) AT-527 1100 mg (4x275 mg)
    Started
    40
    30
    30
    Completed
    40
    29
    30
    Not completed
    0
    1
    0
         Consent withdrawn by subject
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Pooled Placebo
    Reporting group description
    		 Participants received placebo matched to 550 mg or 1100 mg AT-527 twice a day (BID) on Days 1-5.

    Reporting group title
    AT-527 550 mg (1x550 mg)
    Reporting group description
    		 Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.

    Reporting group title
    AT-527 1100 mg (4x275 mg)
    Reporting group description
    		 Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.

    Reporting group values
    		 Pooled Placebo AT-527 550 mg (1x550 mg) AT-527 1100 mg (4x275 mg) Total
    Number of subjects
    		 40 30 30 100
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 36.8 ( 13.2 ) 32.7 ( 10.9 ) 40.3 ( 15.6 ) -
    Sex: Female, Male
    Units:
        Female
    		 22 15 17 54
        Male
    		 18 15 13 46
    Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA at Baseline
    SARS-CoV-2 virus RNA was measured by reverse-transcription polymerase chain reaction (RT-PCR).
    Units: log10 copies/mL
        arithmetic mean (standard deviation)
    		 6.24 ( 1.40 ) 6.98 ( 1.10 ) 5.94 ( 1.46 ) -

    End points

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    End points reporting groups
    Reporting group title
    Pooled Placebo
    Reporting group description
    		 Participants received placebo matched to 550 mg or 1100 mg AT-527 twice a day (BID) on Days 1-5.

    Reporting group title
    AT-527 550 mg (1x550 mg)
    Reporting group description
    		 Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.

    Reporting group title
    AT-527 1100 mg (4x275 mg)
    Reporting group description
    		 Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.

    Subject analysis set title
    Placebo Matched to AT-527 550 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received placebo matched to 550 mg AT-527 twice a day (BID) on Days 1-5.

    Primary: Change from Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 550 mg and Matched Placebo

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    End point title
    		 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 [1]
    End point description
    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. 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. Here, n indicates the number of participants analyzed at each time point.
    End point type
    Primary
    End point timeframe
    Baseline, Day 3, Day 5, Day 7
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Results are reported for the arms as indicated in the endpoint title. The other arms are reported in the co-primary endpoint.
    End point values
    		 AT-527 550 mg (1x550 mg) Placebo Matched to AT-527 550 mg
    Number of subjects analysed
    30
    30
    Units: log10 copies/mL
    arithmetic mean (standard error)
        Day 3 (n=29, 30)
    -1.26 ( 0.206 )
    -1.16 ( 0.203 )
        Day 5 (n=30, 29)
    -2.11 ( 0.226 )
    -2.42 ( 0.230 )
        Day 7 (n=29, 29)
    -3.38 ( 0.220 )
    -3.13 ( 0.220 )
    Statistical analysis title
    		 Day 3
    Comparison groups
    AT-527 550 mg (1x550 mg) v Placebo Matched to AT-527 550 mg
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    P-value
    		 = 0.7144
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    -0.11
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -0.49
         upper limit
    		 0.27
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.292
    Notes
    [2] - A difference in adjusted means of <0 favors RO7496998 (AT-527).
    Statistical analysis title
    		 Day 5
    Comparison groups
    AT-527 550 mg (1x550 mg) v Placebo Matched to AT-527 550 mg
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.3373
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    0.32
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -0.11
         upper limit
    		 0.74
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.327
    Notes
    [3] - A difference in adjusted means of <0 favors RO7496998 (AT-527).
    Statistical analysis title
    		 Day 7
    Comparison groups
    AT-527 550 mg (1x550 mg) v Placebo Matched to AT-527 550 mg
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [4]
    P-value
    		 = 0.426
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    -0.25
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -0.66
         upper limit
    		 0.16
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.315
    Notes
    [4] - A difference in adjusted means of <0 favors RO7496998 (AT-527).

    Primary: Change from Baseline in the Amount of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Virus RNA for AT-527 1100 mg and Pooled Placebo

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    End point title
    		 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 [5]
    End point description
    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. 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. Here, n indicates the number of participants analyzed at each time point.
    End point type
    Primary
    End point timeframe
    Baseline, Day 3, Day 5, Day 7
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Results are reported for the arms as indicated in the endpoint title. The other arms are reported in the co-primary endpoint.
    End point values
    		 Pooled Placebo AT-527 1100 mg (4x275 mg)
    Number of subjects analysed
    40
    30
    Units: log10 copies/mL
    arithmetic mean (standard error)
        Day 3 (n=40, 29)
    -1.08 ( 0.190 )
    -1.18 ( 0.223 )
        Day 5 (n=38, 30)
    -2.21 ( 0.205 )
    -2.31 ( 0.231 )
        Day 7 (n=39, 30)
    -2.70 ( 0.207 )
    -2.78 ( 0.236 )
    Statistical analysis title
    		 Day 3
    Comparison groups
    Pooled Placebo v AT-527 1100 mg (4x275 mg)
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    P-value
    		 = 0.7351
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    -0.1
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -0.48
         upper limit
    		 0.28
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.294
    Notes
    [6] - A difference in adjusted means of <0 favors RO7496998 (AT-527).
    Statistical analysis title
    		 Day 5
    Comparison groups
    Pooled Placebo v AT-527 1100 mg (4x275 mg)
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    P-value
    		 = 0.7524
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    -0.1
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.31
    Notes
    [7] - A difference in adjusted means of <0 favors RO7496998 (AT-527).
    Statistical analysis title
    		 Day 7
    Comparison groups
    Pooled Placebo v AT-527 1100 mg (4x275 mg)
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [8]
    P-value
    		 = 0.8083
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    -0.08
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -0.48
         upper limit
    		 0.33
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.314
    Notes
    [8] - A difference in adjusted means of <0 favors RO7496998 (AT-527).

    Secondary: Time to Cessation of SARS-CoV-2 Viral Shedding

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    End point title
    		 Time to Cessation of SARS-CoV-2 Viral Shedding
    End point description
    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. 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. "99999" indicates that the value was not estimable due to low number of participants with events.
    End point type
    Secondary
    End point timeframe
    Up to Day 7
    End point values
    		 Pooled Placebo AT-527 550 mg (1x550 mg) AT-527 1100 mg (4x275 mg)
    Number of subjects analysed
    40
    30
    30
    Units: hours
        median (inter-quartile range (Q1-Q3))
    99999 (144.2 to 99999)
    99999 (143.8 to 99999)
    99999 (141.1 to 99999)
    Statistical analysis title
    		 Placebo versus AT-527 550 mg
    Statistical analysis description
    Hazard ratio (80% CI) was estimated with a Cox proportional hazards model (unadjusted).
    Comparison groups
    Pooled Placebo v AT-527 550 mg (1x550 mg)
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.96
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.53
         upper limit
    		 1.74
    Statistical analysis title
    		 Placebo versus AT-527 1100 mg
    Statistical analysis description
    Hazard ratio (80% CI) was estimated with a Cox proportional hazards model (unadjusted).
    Comparison groups
    Pooled Placebo v AT-527 1100 mg (4x275 mg)
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.33
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 2.32

    Secondary: Time to Sustained Non-Detectable SARS-CoV-2 Virus RNA

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    End point title
    		 Time to Sustained Non-Detectable SARS-CoV-2 Virus RNA
    End point description
    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. 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. "99999" indicates that the value was not estimable due to low number of participants with events.
    End point type
    Secondary
    End point timeframe
    Up to Day 7
    End point values
    		 Pooled Placebo AT-527 550 mg (1x550 mg) AT-527 1100 mg (4x275 mg)
    Number of subjects analysed
    40
    30
    30
    Units: hours
        median (inter-quartile range (Q1-Q3))
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    Statistical analysis title
    		 Placebo versus AT-527 550 mg
    Statistical analysis description
    Hazard ratio (80% CI) was estimated with a Cox proportional hazards model (unadjusted).
    Comparison groups
    Pooled Placebo v AT-527 550 mg (1x550 mg)
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.86
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.44
         upper limit
    		 1.7
    Statistical analysis title
    		 Placebo versus AT-527 1100 mg
    Statistical analysis description
    Hazard ratio (80% CI) was estimated with a Cox proportional hazards model (unadjusted).
    Comparison groups
    Pooled Placebo v AT-527 1100 mg (4x275 mg)
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.06
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.56
         upper limit
    		 2.03

    Secondary: Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints

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    End point title
    		 Percentage of Participants Positive for SARS-CoV-2 Virus RNA at Specified Timepoints
    End point description
    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. 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. Here, n indicates the number of participants analyzed at each time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 3, Day 5, Day 7
    End point values
    		 Pooled Placebo AT-527 550 mg (1x550 mg) AT-527 1100 mg (4x275 mg)
    Number of subjects analysed
    40
    30
    30
    Units: percentage of participants
    number (not applicable)
        Baseline (n=40, 30, 30)
    100
    100
    96.7
        Day 3 (n=40, 30, 29)
    95.0
    100
    93.1
        Day 5 (n=38, 30, 30)
    84.2
    90.0
    83.3
        Day 7 (n=39, 29, 30)
    76.9
    79.3
    76.7
    Statistical analysis title
    		 Day 3 Placebo versus AT-527 550 mg
    Statistical analysis description
    Confidence interval estimated with the Farrington-Manning method.
    Comparison groups
    Pooled Placebo v AT-527 550 mg (1x550 mg)
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Difference in Percentage of Positivity
    Point estimate
    5
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -0.16
         upper limit
    		 10.16
    Statistical analysis title
    		 Day 3 Placebo versus AT-527 1100 mg
    Statistical analysis description
    Confidence interval estimated with the Farrington-Manning method.
    Comparison groups
    Pooled Placebo v AT-527 1100 mg (4x275 mg)
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Difference in Percentage of Positivity
    Point estimate
    -1.9
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -9.2
         upper limit
    		 5.41
    Statistical analysis title
    		 Day 5 Placebo versus AT-527 550 mg
    Statistical analysis description
    Confidence interval estimated with the Farrington-Manning method.
    Comparison groups
    Pooled Placebo v AT-527 550 mg (1x550 mg)
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Difference in Percentage of Positivity
    Point estimate
    5.79
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -4.82
         upper limit
    		 16.4
    Statistical analysis title
    		 Day 5 Placebo versus AT-527 1100 mg
    Statistical analysis description
    Confidence interval estimated with the Farrington-Manning method.
    Comparison groups
    Pooled Placebo v AT-527 1100 mg (4x275 mg)
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Difference in Percentage of Positivity
    Point estimate
    -0.88
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -12.4
         upper limit
    		 10.65
    Statistical analysis title
    		 Day 7 Placebo versus AT-527 550 mg
    Statistical analysis description
    Confidence interval estimated with the Farrington-Manning method.
    Comparison groups
    Pooled Placebo v AT-527 550 mg (1x550 mg)
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Difference in Percentage of Positivity
    Point estimate
    2.39
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -10.64
         upper limit
    		 15.42
    Statistical analysis title
    		 Day 7 Placebo versus AT-527 1100 mg
    Statistical analysis description
    Confidence interval estimated with the Farrington-Manning method.
    Comparison groups
    Pooled Placebo v AT-527 1100 mg (4x275 mg)
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Difference in Percentage of Positivity
    Point estimate
    -0.26
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -13.39
         upper limit
    		 12.88

    Secondary: Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA

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    End point title
    		 Area Under the Curve (AUC) in the Amount of SARS-CoV-2 Virus RNA
    End point description
    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. 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.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 3, Day 5, Day 7
    End point values
    		 Pooled Placebo AT-527 550 mg (1x550 mg) AT-527 1100 mg (4x275 mg)
    Number of subjects analysed
    40
    30
    30
    Units: log10 copies/mL*hour
        arithmetic mean (standard deviation)
    651.56 ( 189.10 )
    733.70 ( 146.63 )
    618.62 ( 194.88 )
    No statistical analyses for this end point

    Secondary: Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 hours)

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    End point title
    		 Time to Alleviation or Improvement of COVID-19 Symptoms (21.5 hours)
    End point description
    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. mITTi population was analyzed for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to 28 Days
    End point values
    		 Pooled Placebo AT-527 550 mg (1x550 mg) AT-527 1100 mg (4x275 mg)
    Number of subjects analysed
    40
    30
    30
    Units: hours
        median (inter-quartile range (Q1-Q3))
    43.4 (9.3 to 104.7)
    57.2 (9.0 to 115.8)
    56.4 (2.5 to 96.4)
    No statistical analyses for this end point

    Secondary: Time to Alleviation or Improvement of COVID-19 Symptoms (43 hours)

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    End point title
    		 Time to Alleviation or Improvement of COVID-19 Symptoms (43 hours)
    End point description
    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. mITTi population was analyzed for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to 28 Days
    End point values
    		 Pooled Placebo AT-527 550 mg (1x550 mg) AT-527 1100 mg (4x275 mg)
    Number of subjects analysed
    40
    30
    30
    Units: hours
        median (inter-quartile range (Q1-Q3))
    43.4 (9.3 to 104.7)
    57.2 (9.0 to 141.2)
    58.1 (2.5 to 118.2)
    No statistical analyses for this end point

    Secondary: Time to Alleviation of COVID-19 Symptoms (21.5 hours)

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    End point title
    		 Time to Alleviation of COVID-19 Symptoms (21.5 hours)
    End point description
    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. mITTi population was analyzed for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to 28 Days
    End point values
    		 Pooled Placebo AT-527 550 mg (1x550 mg) AT-527 1100 mg (4x275 mg)
    Number of subjects analysed
    40
    30
    30
    Units: hours
        median (inter-quartile range (Q1-Q3))
    43.4 (9.3 to 104.7)
    57.2 (9.0 to 115.8)
    56.4 (8.2 to 96.4)
    No statistical analyses for this end point

    Secondary: Time to Alleviation of COVID-19 Symptoms (43 hours)

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    End point title
    		 Time to Alleviation of COVID-19 Symptoms (43 hours)
    End point description
    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. mITTi population was analyzed for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to 28 Days
    End point values
    		 Pooled Placebo AT-527 550 mg (1x550 mg) AT-527 1100 mg (4x275 mg)
    Number of subjects analysed
    40
    30
    30
    Units: hours
        median (inter-quartile range (Q1-Q3))
    43.4 (9.3 to 104.7)
    57.2 (9.0 to 141.2)
    58.1 (8.2 to 118.2)
    No statistical analyses for this end point

    Secondary: Duration of Fever

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    End point title
    		 Duration of Fever
    End point description
    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. 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.
    End point type
    Secondary
    End point timeframe
    Up to 28 Days
    End point values
    		 Pooled Placebo AT-527 550 mg (1x550 mg) AT-527 1100 mg (4x275 mg)
    Number of subjects analysed
    2 [9]
    0 [10]
    0 [11]
    Units: hours
        median (inter-quartile range (Q1-Q3))
    10.6 (9.6 to 11.7)
    ( to )
    ( to )
    Notes
    [9] - Only participants who had a fever (temperature > 37.5 degrees Celsius) at baseline are included.
    [10] - Only participants who had a fever (temperature > 37.5 degrees Celsius) at baseline are included.
    [11] - Only participants who had a fever (temperature > 37.5 degrees Celsius) at baseline are included.
    No statistical analyses for this end point

    Secondary: Percentage of Participants with COVID-19 Related Complications

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    End point title
    		 Percentage of Participants with COVID-19 Related Complications
    End point description
    COVID-19 related complications include death, hospitalization, radiologically confirmed pneumonia, acute respiratory failure, sepsis, coagulopathy, pericarditis, myocarditis, and cardiac failure. 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.
    End point type
    Secondary
    End point timeframe
    Up to 33 Days
    End point values
    		 Pooled Placebo AT-527 550 mg (1x550 mg) AT-527 1100 mg (4x275 mg)
    Number of subjects analysed
    40
    30
    30
    Units: percentage of participants
        number (not applicable)
    0
    3.3
    3.3
    No statistical analyses for this end point

    Secondary: Time to Alleviation of an Individual Symptom

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    End point title
    		 Time to Alleviation of an Individual Symptom
    End point description
    The COVID-19 Symptom Diary included 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, 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: the time from the start of treatment to the point at which the following criterion was met and maintained for at least 21.5 hours: score of 0 or 1 for Items 1-12; score of 0 for Items 13-14. mITTi population: only participants with a baseline score of > 1 for Items 1 - 12 or > 0 for Items 13 - 14 were included in the analysis. Here, "n" is the number of participants analyzed for the individual symptom. "99999": not estimable due to low number of events.
    End point type
    Secondary
    End point timeframe
    Up to 28 Days
    End point values
    		 Pooled Placebo AT-527 550 mg (1x550 mg) AT-527 1100 mg (4x275 mg)
    Number of subjects analysed
    40
    30
    30
    Units: hours
    median (inter-quartile range (Q1-Q3))
        Nasal Congestion/Runny Nose (n=12, 8, 10)
    27.6 (11.3 to 59.9)
    34.2 (15.8 to 82.4)
    32.7 (10.0 to 57.7)
        Sore Throat (n=5, 5, 2)
    20.5 (14.1 to 22.7)
    24.1 (9.8 to 45.0)
    111.7 (22.1 to 201.4)
        Cough (n=11, 6, 7)
    22.6 (11.8 to 129.3)
    90.7 (23.7 to 140.4)
    33.9 (20.5 to 119.2)
        Shortness of Breath (n=3, 2, 1)
    23.9 (11.5 to 99999)
    68.9 (68.5 to 69.2)
    11.6 (11.6 to 11.6)
        Aches and Pains (n=8, 8, 4)
    33.1 (11.8 to 60.4)
    22.3 (16.3 to 62.2)
    94.4 (48.1 to 177.7)
        Fatigue (n=15, 10, 11)
    47.8 (22.6 to 178.1)
    44.4 (10.5 to 94.5)
    70.6 (22.6 to 106.0)
        Headache (n=13, 7, 11)
    32.0 (10.1 to 95.8)
    11.7 (9.8 to 93.6)
    34.4 (21.8 to 105.4)
        Chills/Sweats (n=8, 3, 4)
    11.8 (9.8 to 24.1)
    12.0 (9.0 to 35.8)
    25.0 (17.1 to 41.4)
        Feeling Hot or Feverish (n=6, 2, 4)
    26.5 (11.8 to 35.7)
    48.0 (24.0 to 72.0)
    40.3 (15.9 to 63.4)
        Nausea (n=2, 0, 0)
    99999 (21.1 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        Vomiting (n=2, 0, 0)
    99999 (11.0 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        Diarrhea (n=1, 0, 1)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    9.8 (9.8 to 9.8)
        Sense of Smell (n=19, 14, 18)
    261.5 (164.9 to 99999)
    290.2 (130.7 to 99999)
    213.1 (129.7 to 513.7)
        Sense of Taste (n=16, 12, 17)
    221.1 (165.3 to 297.6)
    214.1 (94.1 to 99999)
    178.5 (105.5 to 391.2)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Adverse Events (AEs)

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    End point title
    		 Percentage of Participants with Adverse Events (AEs)
    End point description
    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. 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.
    End point type
    Secondary
    End point timeframe
    Up to 33 Days
    End point values
    		 Pooled Placebo AT-527 550 mg (1x550 mg) AT-527 1100 mg (4x275 mg)
    Number of subjects analysed
    40
    30
    30
    Units: percentage of participants
        number (not applicable)
    27.5
    20.0
    33.3
    No statistical analyses for this end point

    Secondary: Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated with 550 mg AT-527

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    End point title
    		 Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated with 550 mg AT-527 [12]
    End point description
    AT-511 is the free base form of AT-527. Its major metabolites are AT-551, AT-229, and AT-273. 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. Here, n indicates the number of participants analyzed at each time point.
    End point type
    Secondary
    End point timeframe
    Day 1: pre-dose, 1 hour, 3 hours; Day 3: pre-dose; Day 5: pre-dose, 3 hours, 48 hours
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Results are presented for the arm as indicated in the endpoint title. Plasma concentrations were only evaluated in the arms treated with AT-527.
    End point values
    		 AT-527 550 mg (1x550 mg)
    Number of subjects analysed
    30
    Units: nanograms per milliliter (ng/mL)
    arithmetic mean (standard deviation)
        AT-511: Day 1, pre-dose (n=30)
    1.3 ( 4.5 )
        AT-511: Day 1, 1 hour (n=30)
    1950.5 ( 2365.0 )
        AT-511: Day 1, 3 hours (n=29)
    441.4 ( 645.8 )
        AT-511: Day 3, pre-dose (n=28)
    254.2 ( 943.1 )
        AT-511: Day 5, pre-dose (n=30)
    5.6 ( 21.9 )
        AT-511: Day 5, 3 hours (n=30)
    415.7 ( 445.5 )
        AT-511: Day 5, 48 hours (n=29)
    0.5 ( 0.0 )
        AT-551: Day 1, pre-dose (n=30)
    0.5 ( 0.0 )
        AT-551: Day 1, 1 hour (n=30)
    347.5 ( 334.1 )
        AT-551: Day 1, 3 hours (n=29)
    375.8 ( 303.9 )
        AT-551: Day 3, pre-dose (n=28)
    56.9 ( 100.1 )
        AT-551: Day 5, pre-dose (n=30)
    26.6 ( 22.7 )
        AT-551: Day 5, 3 hours (n=30)
    323.8 ( 168.3 )
        AT-551: Day 5, 48 hours (n=29)
    1.7 ( 1.4 )
        AT-229: Day 1, pre-dose (n=30)
    0.5 ( 0.0 )
        AT-229: Day 1, 1 hour (n=30)
    268.5 ( 318.5 )
        AT-229: Day 1, 3 hours (n=29)
    427.4 ( 275.8 )
        AT-229: Day 3, pre-dose (n=28)
    290.3 ( 152.3 )
        AT-229: Day 5, pre-dose (n=30)
    295.4 ( 145.0 )
        AT-229: Day 5, 3 hours (n=30)
    773.9 ( 340.8 )
        AT-229: Day 5, 48 hours (n=29)
    89.2 ( 87.8 )
        AT-273: Day 1, pre-dose (n=30)
    0.5 ( 0.0 )
        AT-273: Day 1, 1 hour (n=30)
    26.5 ( 29.0 )
        AT-273: Day 1, 3 hours (n=29)
    132.2 ( 66.7 )
        AT-273: Day 3, pre-dose (n=28)
    135.9 ( 47.6 )
        AT-273: Day 5, pre-dose (n=30)
    138.1 ( 53.0 )
        AT-273: Day 5, 3 hours (n=30)
    236.9 ( 79.9 )
        AT-273: Day 5, 48 hours (n=29)
    40.9 ( 22.7 )
    No statistical analyses for this end point

    Secondary: Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated with 1100 mg AT-527

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    End point title
    		 Plasma Concentrations of AT-511, AT-551, AT-229 and AT-273 for Participants Treated with 1100 mg AT-527 [13]
    End point description
    AT-511 is the free base form of AT-527. Its major metabolites are AT-551, AT-229, and AT-273. 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. Here, n indicates the number of participants analyzed at each time point.
    End point type
    Secondary
    End point timeframe
    Day 1: pre-dose, 1 hour, 4 hours; Day 3: pre-dose; Day 5: pre-dose, 1 hour, 4 hours, 48 hours
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Results are presented for the arm as indicated in the endpoint title. Plasma concentrations were only evaluated in the arms treated with AT-527.
    End point values
    		 AT-527 1100 mg (4x275 mg)
    Number of subjects analysed
    30
    Units: nanograms per milliliter (ng/mL)
    arithmetic mean (standard deviation)
        AT-511: Day 1, pre-dose (n=29)
    0.5 ( 0.0 )
        AT-511: Day 1, 1 hour (n=29)
    3575.0 ( 2883.6 )
        AT-511: Day 1, 4 hours (n=30)
    852.4 ( 1513.2 )
        AT-511: Day 3, pre-dose (n=24)
    9.6 ( 15.9 )
        AT-511: Day 5, pre-dose (n=26)
    316.7 ( 1544.7 )
        AT-511: Day 5, 1 hour (n=25)
    3568.9 ( 3352.1 )
        AT-511: Day 5, 4 hours (n=23)
    1323.3 ( 2883.5 )
        AT-511: Day 5, 48 hours (n=24)
    0.6 ( 0.6 )
        AT-551: Day 1, pre-dose (n=29)
    0.5 ( 0.0 )
        AT-551: Day 1, 1 hour (n=29)
    592.2 ( 576.9 )
        AT-551: Day 1, 4 hours (n=30)
    640.4 ( 446.3 )
        AT-551: Day 3, pre-dose (n=25)
    84.0 ( 72.1 )
        AT-551: Day 5, pre-dose (n=26)
    71.3 ( 61.6 )
        AT-551: Day 5, 1 hour (n=25)
    302.8 ( 222.1 )
        AT-551: Day 5, 4 hours (n=23)
    342.1 ( 254.9 )
        AT-551: Day 5, 48 hours (n=24)
    4.4 ( 4.8 )
        AT-229: Day 1, pre-dose (n=29)
    0.5 ( 0.0 )
        AT-229: Day 1, 1 hour (n=29)
    371.9 ( 460.3 )
        AT-229: Day 1, 4 hours (n=30)
    865.4 ( 494.2 )
        AT-229: Day 3, pre-dose (n=25)
    682.8 ( 351.7 )
        AT-229: Day 5, pre-dose (n=26)
    797.8 ( 459.9 )
        AT-229: Day 5, 1 hour (n=25)
    990.9 ( 505.3 )
        AT-229: Day 5, 4 hours (n=23)
    1357.2 ( 825.3 )
        AT-229: Day 5, 48 hours (n=24)
    279.4 ( 285.3 )
        AT-273: Day 1, pre-dose (n=29)
    0.5 ( 0.0 )
        AT-273: Day 1, 1 hour (n=29)
    35.7 ( 47.4 )
        AT-273: Day 1, 4 hours (n=30)
    231.8 ( 111.4 )
        AT-273: Day 3, pre-dose (n=25)
    245.6 ( 122.8 )
        AT-273: Day 5, pre-dose (n=26)
    263.6 ( 107.3 )
        AT-273: Day 5, 1 hour (n=25)
    252.1 ( 97.4 )
        AT-273: Day 5, 4 hours (n=23)
    310.6 ( 107.5 )
        AT-273: Day 5, 48 hours (n=24)
    84.4 ( 45.5 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 33 days
    Adverse event reporting additional description
    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.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Pooled Placebo
    Reporting group description
    		 Participants received placebo matched to 550 mg or 1100 mg AT-527 twice a day (BID) on Days 1-5.

    Reporting group title
    AT-527 1100 mg (4x275 mg)
    Reporting group description
    		 Participants received 1100 mg AT-527 (4x275 mg) twice a day (BID) on Days 1-5.

    Reporting group title
    AT-527 550 mg (1x550 mg)
    Reporting group description
    		 Participants received 550 mg AT-527 (1x550 mg) twice a day (BID) on Days 1-5.

    Serious adverse events
    		 Pooled Placebo AT-527 1100 mg (4x275 mg) AT-527 550 mg (1x550 mg)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 30 (3.33%)
    1 / 30 (3.33%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Cardiac disorders
    Atrial flutter
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 30 (3.33%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Pooled Placebo AT-527 1100 mg (4x275 mg) AT-527 550 mg (1x550 mg)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1 / 40 (2.50%)
    5 / 30 (16.67%)
    1 / 30 (3.33%)
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    1 / 40 (2.50%)
    3 / 30 (10.00%)
    1 / 30 (3.33%)
         occurrences all number
    1
    3
    1
    Vomiting
         subjects affected / exposed
    1 / 40 (2.50%)
    5 / 30 (16.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    5
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Dec 2020
    The purpose of amendment version 2 was primarily to remove the use of historical severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) test results for eligibility assessment and to clarify the timing of safety data required for dose-selection decision making.
    05 Feb 2021
    The purpose of country-specific amendment version 3 was to incorporate changes requested by the Irish Health Products Regulatory Authority.
    24 Feb 2021
    The purpose of amendment version 4 was primarily to broaden the patient population by allowing all subjects with mild or moderate COVID-19 to be enrolled, not only those considered otherwise healthy, and to enable Cohorts B-E to be conducted in an outpatient setting. The parameters for the dose selection decision were also modified.
    13 May 2021
    The purpose of amendment version 5 was primarily to incorporate additional secondary efficacy endpoints and updated information related to cautionary therapies.
    17 Sep 2021
    The purpose of amendment version 6 was primarily to enable further evaluation of the antiviral efficacy and safety of RO7496998 (AT-527) using the dose regimen selected from previous cohorts. No patients were enrolled under this protocol version as the study closed after recruitment of Cohort A and Cohort B.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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