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    Clinical Trial Results:
    A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Assessing the Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies in Preventing SARS-CoV-2 Infection in Household Contacts of Individuals Infected with SARS-CoV-2

    Summary
    EudraCT number
    2020-003654-71
    Trial protocol
    RO   GR  
    Global end of trial date
    04 Oct 2021

    Results information
    Results version number
    v1(current)
    This version publication date
    18 Apr 2022
    First version publication date
    18 Apr 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    R10933-10987-COV-2069
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Regeneron Pharmaceuticals, Inc.
    Sponsor organisation address
    777 Old Saw Mill River Rd., Tarrytown, United States, 10591
    Public contact
    Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 8447346643, clinicaltrials@regeneron.com
    Scientific contact
    Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 8447346643, clinicaltrials@regeneron.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-002964-PIP01-21, EMEA-002964-PIP01-21
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    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
    04 Oct 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Oct 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This randomized, double-blind, placebo-controlled master protocol assessed the safety, tolerability, and efficacy of casirivimab+imdevimab in adult subjects and pediatric subjects who are household contacts of the first known household member infected with SARS-CoV-2 (index case).
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the International Conference on Harmonisation (ICH) guidelines for Good Clinical Practice (GCP) and applicable regulatory requirements.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    13 Jul 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Moldova, Republic of: 126
    Country: Number of subjects enrolled
    United States: 3075
    Country: Number of subjects enrolled
    Romania: 97
    Worldwide total number of subjects
    3298
    EEA total number of subjects
    97
    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)
    1
    Adolescents (12-17 years)
    145
    Adults (18-64 years)
    2867
    From 65 to 84 years
    274
    85 years and over
    11

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Of 3375 participants screened, 3298 participants were randomized and 3270 participants were treated. 77 participants were screen failures and 28 participants were randomized but not treated.

    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, Monitor, Carer, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort A: Placebo of R10933 + R10987
    Arm description
    Cohort A: Placebo of R10933 + R10987 Adult and Adolescent Subjects (≥12years) Who Are SARS-CoV-2 RT-qPCR negative at baseline
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo for casirivimab and placebo for imdevimab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1 to 4 injections in the abdomen or thigh • SC: For adults and pediatric participants ≥10 kg. Investigators had the option to use an infusion pump for SC administration of study drug containing the combined volume with both mAbs.

    Arm title
    Cohort A: R10933 + R10987
    Arm description
    Cohort A: R10933 + R10987 Adult and Adolescent Subjects (≥12years) Who Are SARS-CoV-2 RT-qPCR negative at baseline
    Arm type
    Experimental

    Investigational medicinal product name
    casirivimab (REGN10933) and imdevimab (REGN10987)
    Investigational medicinal product code
    R10933 + R10987
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1 to 4 injections in the abdomen or thigh • SC: For adults and pediatric participants ≥10 kg. Investigators had the option to use an infusion pump for SC administration of study drug containing the combined volume with both mAbs.

    Arm title
    Cohort A1: Placebo of R10933 + R10987
    Arm description
    Cohort A1: Placebo of R10933 + R10987 Pediatric Subjects (<12 years) with SARS-CoV-2 RT-qPCR Negative
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo for casirivimab and placebo for imdevimab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1 to 4 injections in the abdomen or thigh • SC: pediatric participants ≥10 kg. Investigators had the option to use an infusion pump for SC administration of study drug containing the combined volume with both mAbs.

    Arm title
    Cohort B: Placebo of R10933 + R10987
    Arm description
    Cohort B: Placebo of R10933 + R10987 Adult and Adolescent Subjects (≥12years) Who Are SARS-CoV-2 RT-qPCR Positive
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo for casirivimab and placebo for imdevimab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1 to 4 injections in the abdomen or thigh • SC: For adults and pediatric participants ≥10 kg. Investigators had the option to use an infusion pump for SC administration of study drug containing the combined volume with both mAbs.

    Arm title
    Cohort B: R10933 + R10987
    Arm description
    Cohort B: R10933 + R10987 Adult and Adolescent Subjects (≥12years) who Are SARS-CoV-2 RT-qPCR Positive
    Arm type
    Experimental

    Investigational medicinal product name
    casirivimab (REGN10933) and imdevimab (REGN10987)
    Investigational medicinal product code
    R10933 + R10987
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1 to 4 injections in the abdomen or thigh • SC: For adults and pediatric participants ≥10 kg. Investigators had the option to use an infusion pump for SC administration of study drug containing the combined volume with both mAbs.

    Arm title
    Undetermined: Placebo of R10933 + R10987
    Arm description
    Undetermined: Placebo of R10933 + R10987 Adult and Adolescent subjects (≥12 years) whose baseline RT-qPCR status was inconclusive or missing
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo for casirivimab and placebo for imdevimab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1 to 4 injections in the abdomen or thigh • SC: For adults and pediatric participants ≥10 kg. Investigators had the option to use an infusion pump for SC administration of study drug containing the combined volume with both mAbs.

    Arm title
    Undetermined: R10933 + R10987
    Arm description
    Undetermined: R10933 + R10987 Adult and Adolescent subjects (≥12 years) whose baseline RT-qPCR status was inconclusive or missing
    Arm type
    Experimental

    Investigational medicinal product name
    casirivimab (REGN10933) and imdevimab (REGN10987)
    Investigational medicinal product code
    R10933 + R10987
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1 to 4 injections in the abdomen or thigh • SC: For adults and pediatric participants ≥10 kg. Investigators had the option to use an infusion pump for SC administration of study drug containing the combined volume with both mAbs.

    Number of subjects in period 1
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987 Cohort A1: Placebo of R10933 + R10987 Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987 Undetermined: Placebo of R10933 + R10987 Undetermined: R10933 + R10987
    Started
    1430
    1441
    1
    173
    166
    53
    34
    Randomized and treated
    1428
    1439
    1
    170
    165
    44
    23
    Completed
    1343
    1368
    1
    150
    157
    41
    22
    Not completed
    87
    73
    0
    23
    9
    12
    12
         Physician decision
    1
    2
    -
    2
    -
    2
    5
         Adverse event, serious fatal
    2
    3
    -
    -
    -
    -
    -
         Consent withdrawn by subject
    46
    40
    -
    18
    6
    8
    6
         Lost to follow-up
    38
    28
    -
    3
    3
    2
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort A: Placebo of R10933 + R10987
    Reporting group description
    Cohort A: Placebo of R10933 + R10987 Adult and Adolescent Subjects (≥12years) Who Are SARS-CoV-2 RT-qPCR negative at baseline

    Reporting group title
    Cohort A: R10933 + R10987
    Reporting group description
    Cohort A: R10933 + R10987 Adult and Adolescent Subjects (≥12years) Who Are SARS-CoV-2 RT-qPCR negative at baseline

    Reporting group title
    Cohort A1: Placebo of R10933 + R10987
    Reporting group description
    Cohort A1: Placebo of R10933 + R10987 Pediatric Subjects (<12 years) with SARS-CoV-2 RT-qPCR Negative

    Reporting group title
    Cohort B: Placebo of R10933 + R10987
    Reporting group description
    Cohort B: Placebo of R10933 + R10987 Adult and Adolescent Subjects (≥12years) Who Are SARS-CoV-2 RT-qPCR Positive

    Reporting group title
    Cohort B: R10933 + R10987
    Reporting group description
    Cohort B: R10933 + R10987 Adult and Adolescent Subjects (≥12years) who Are SARS-CoV-2 RT-qPCR Positive

    Reporting group title
    Undetermined: Placebo of R10933 + R10987
    Reporting group description
    Undetermined: Placebo of R10933 + R10987 Adult and Adolescent subjects (≥12 years) whose baseline RT-qPCR status was inconclusive or missing

    Reporting group title
    Undetermined: R10933 + R10987
    Reporting group description
    Undetermined: R10933 + R10987 Adult and Adolescent subjects (≥12 years) whose baseline RT-qPCR status was inconclusive or missing

    Reporting group values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987 Cohort A1: Placebo of R10933 + R10987 Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987 Undetermined: Placebo of R10933 + R10987 Undetermined: R10933 + R10987 Total
    Number of subjects
    1430 1441 1 173 166 53 34 3298
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0 0 0 0 0
        Newborns (0-27 days)
    0 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0 0 0 0 0
        Children (2-11 years)
    0 0 1 0 0 0 0 1
        Adolescents (12-17 years)
    47 52 0 20 23 2 1 145
        Adults (18-64 years)
    1272 1263 0 130 127 45 30 2867
        From 65-84 years
    105 125 0 21 15 5 3 274
        85 years and over
    6 1 0 2 1 1 0 11
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    42.4 ± 15.71 42.1 ± 15.99 10.0 ± 0.0 41.8 ± 18.1 39.5 ± 17.81 41.8 ± 16.73 39.0 ± 15.3 -
    Sex: Female, Male
    Units: participants
        Female
    738 780 0 97 80 21 20 1736
        Male
    692 661 1 76 86 32 14 1562
    Race/Ethnicity, Customized
    Units: Subjects
        White
    1193 1196 1 149 140 46 29 2754
        Black or African American
    161 164 0 11 9 4 1 350
        Asian
    37 42 0 8 11 3 2 103
        American Indian or Alaska Native
    5 4 0 1 1 0 0 11
        Native Hawaiian or Other Pacific Islander
    2 3 0 0 0 0 0 5
        Other
    32 32 0 4 5 0 2 75

    End points

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    End points reporting groups
    Reporting group title
    Cohort A: Placebo of R10933 + R10987
    Reporting group description
    Cohort A: Placebo of R10933 + R10987 Adult and Adolescent Subjects (≥12years) Who Are SARS-CoV-2 RT-qPCR negative at baseline

    Reporting group title
    Cohort A: R10933 + R10987
    Reporting group description
    Cohort A: R10933 + R10987 Adult and Adolescent Subjects (≥12years) Who Are SARS-CoV-2 RT-qPCR negative at baseline

    Reporting group title
    Cohort A1: Placebo of R10933 + R10987
    Reporting group description
    Cohort A1: Placebo of R10933 + R10987 Pediatric Subjects (<12 years) with SARS-CoV-2 RT-qPCR Negative

    Reporting group title
    Cohort B: Placebo of R10933 + R10987
    Reporting group description
    Cohort B: Placebo of R10933 + R10987 Adult and Adolescent Subjects (≥12years) Who Are SARS-CoV-2 RT-qPCR Positive

    Reporting group title
    Cohort B: R10933 + R10987
    Reporting group description
    Cohort B: R10933 + R10987 Adult and Adolescent Subjects (≥12years) who Are SARS-CoV-2 RT-qPCR Positive

    Reporting group title
    Undetermined: Placebo of R10933 + R10987
    Reporting group description
    Undetermined: Placebo of R10933 + R10987 Adult and Adolescent subjects (≥12 years) whose baseline RT-qPCR status was inconclusive or missing

    Reporting group title
    Undetermined: R10933 + R10987
    Reporting group description
    Undetermined: R10933 + R10987 Adult and Adolescent subjects (≥12 years) whose baseline RT-qPCR status was inconclusive or missing

    Subject analysis set title
    Anti-drug Antibodies Analysis Set (AAS)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    The Anti-drug Antibodies Analysis set (AAS) includes all treated subjects who received study drug and had at least 1 non-missing ADA result after study drug administration. The AAS is based on the actual treatment received.

    Subject analysis set title
    NAb Analysis Set
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    NAb analysis set includes all treated subjects who received any study drug (active or placebo), have at least one non-missing anti-casirivimab or anti-imdevimab antibody result following the first dose of study drug (active or placebo), and either tested negative at all ADA sampling times or tested positive for ADA with at least one non-missing NAb result after first dose of the study drug (active or placebo).

    Subject analysis set title
    PKAS Analysis Set
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    PK analysis set (PKAS) includes all treated subjects who received any study drug and had at least 1 non-missing casirivimab or imdevimab concentration measurement following study drug administration, respectively. The PK analysis set is based on the actual treatment received (as treated) rather than as randomized.

    Primary: Cohort A: Percentage of participants who have a symptomatic RT-qPCR confirmed SARS-CoV-2 infection (broad-term) during the EAP

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    End point title
    Cohort A: Percentage of participants who have a symptomatic RT-qPCR confirmed SARS-CoV-2 infection (broad-term) during the EAP [1]
    End point description
    Symptomatic SARS-CoV-2 infection (broad-term) is defined as a positive central lab SARS-CoV-2 RT-qPCR result (either NP, nasal or saliva) associated with signs and symptoms with the onset date occurring within 14 days of a positive RT-qPCR during the EAP. Percentage estimated by Logistic Regression.
    End point type
    Primary
    End point timeframe
    Up to 1 month
    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: This endpoint is only applicable to participants in Cohort A.
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    752
    753
    Units: Percentage of Participants
        number (not applicable)
    7.8
    1.4
    Statistical analysis title
    Cohort A: R10933 + R10987 and Placebo
    Comparison groups
    Cohort A: R10933 + R10987 v Cohort A: Placebo of R10933 + R10987
    Number of subjects included in analysis
    1505
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.17
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.09
         upper limit
    0.332

    Primary: Cohort B: Percentage of Participants who Subsequently Develop Signs and Symptoms (Broad-Term) within 14 Days of a Positive RT-qPCR at Baseline or during the EAP

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    End point title
    Cohort B: Percentage of Participants who Subsequently Develop Signs and Symptoms (Broad-Term) within 14 Days of a Positive RT-qPCR at Baseline or during the EAP [2]
    End point description
    End point type
    Primary
    End point timeframe
    Up to 8 months
    Notes
    [2] - 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: This endpoint is only applicable to participants in Cohort B
    End point values
    Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    104
    100
    Units: Percentage of Participants
        number (not applicable)
    42.5
    28.4
    Statistical analysis title
    Cohort B: R10933 + R10987 and Placebo
    Comparison groups
    Cohort B: R10933 + R10987 v Cohort B: Placebo of R10933 + R10987
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.038
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.54
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.298
         upper limit
    0.966

    Primary: Cohort A and Cohort B: Number of participants with at least one treatment-emergent adverse event (TEAEs) and severity of TEAEs

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    End point title
    Cohort A and Cohort B: Number of participants with at least one treatment-emergent adverse event (TEAEs) and severity of TEAEs [3] [4]
    End point description
    End point type
    Primary
    End point timeframe
    Up to 8 months
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint is only applicable to participants in Cohort A
    [4] - 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: This endpoint is only applicable to participants in Cohort A and Cohort B.
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987 Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    1428
    1439
    170
    165
    Units: Participants
        # of participants with at least one TEAE
    512
    405
    88
    60
        # of participants with at least one Grade 1 TEAE
    384
    284
    61
    51
        # of participants with at least one Grade 2 TEAE
    98
    95
    21
    7
        # of participants with at least one Grade 3 TEAE
    26
    21
    6
    2
        # of participants with at least one Grade 4 TEAE
    2
    2
    0
    0
        # of participants with at least one Grade 5 TEAE
    2
    3
    0
    0
    No statistical analyses for this end point

    Secondary: Cohort A and Cohort B: Percentage of Participants with high viral load in Nasopharyngeal (NP) swab samples during the EAP

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    End point title
    Cohort A and Cohort B: Percentage of Participants with high viral load in Nasopharyngeal (NP) swab samples during the EAP [5]
    End point description
    High viral load (> 4 log 10 copies/ml)
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    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: This endpoint is only applicable to participants in Cohort A and Cohort B.
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987 Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    749
    745
    101
    98
    Units: Percentage of Participants
        number (not applicable)
    11.3
    1.6
    62.6
    40.5
    Statistical analysis title
    Cohort A: R10933 + R10987 and Placebo
    Comparison groups
    Cohort A: R10933 + R10987 v Cohort A: Placebo of R10933 + R10987
    Number of subjects included in analysis
    1494
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.13
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.069
         upper limit
    0.236
    Statistical analysis title
    Cohort B: R10933 + R10987 and Placebo
    Comparison groups
    Cohort B: R10933 + R10987 v Cohort B: Placebo of R10933 + R10987
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0024
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.41
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.228
         upper limit
    0.728

    Secondary: Cohort A: Number of weeks of symptomatic RT-qPCR confirmed SARS-CoV-2 infection (broad term) during the EAP

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    End point title
    Cohort A: Number of weeks of symptomatic RT-qPCR confirmed SARS-CoV-2 infection (broad term) during the EAP [6]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [6] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    752
    753
    Units: weeks
        arithmetic mean (standard deviation)
    0.25 ± 1.135
    0.02 ± 0.181
    Statistical analysis title
    Cohort A: R10933 + R10987 and Placebo
    Comparison groups
    Cohort A: R10933 + R10987 v Cohort A: Placebo of R10933 + R10987
    Number of subjects included in analysis
    1505
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Cohort A and Cohort B: Number of weeks of high viral load in NP swab samples during the EAP

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    End point title
    Cohort A and Cohort B: Number of weeks of high viral load in NP swab samples during the EAP [7]
    End point description
    High viral load (> 4 log 10 copies/ml)
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [7] - 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: This endpoint is only applicable to participants in Cohort A and Cohort B.
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987 Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    749
    745
    101
    98
    Units: weeks
        arithmetic mean (standard deviation)
    0.18 ± 0.554
    0.02 ± 0.154
    0.81 ± 0.758
    0.49 ± 0.677
    Statistical analysis title
    Cohort B: R10933 + R10987 and Placebo
    Comparison groups
    Cohort B: Placebo of R10933 + R10987 v Cohort B: R10933 + R10987
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    Cohort A: R10933 + R10987 and Placebo
    Comparison groups
    Cohort A: Placebo of R10933 + R10987 v Cohort A: R10933 + R10987
    Number of subjects included in analysis
    1494
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Cohort A: Number of weeks of RT-qPCR confirmed SARS-CoV-2 infection (regardless of symptoms) during the EAP

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    End point title
    Cohort A: Number of weeks of RT-qPCR confirmed SARS-CoV-2 infection (regardless of symptoms) during the EAP [8]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [8] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    752
    753
    Units: weeks
        arithmetic mean (standard deviation)
    0.31 ± 0.854
    0.05 ± 0.260
    Statistical analysis title
    Cohort A: R10933 + R10987 and Placebo
    Comparison groups
    Cohort A: R10933 + R10987 v Cohort A: Placebo of R10933 + R10987
    Number of subjects included in analysis
    1505
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Cohort A: Percentage of participants who have a RT-qPCR confirmed SARS-CoV-2 infection (regardless of symptoms) during the EAP

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    End point title
    Cohort A: Percentage of participants who have a RT-qPCR confirmed SARS-CoV-2 infection (regardless of symptoms) during the EAP [9]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [9] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    752
    753
    Units: Percentage of Participants
        number (not applicable)
    14.56
    5.00
    Statistical analysis title
    Cohort A: R10933 + R10987 and Placebo
    Comparison groups
    Cohort A: R10933 + R10987 v Cohort A: Placebo of R10933 + R10987
    Number of subjects included in analysis
    1505
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.31
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.208
         upper limit
    0.456

    Secondary: Cohort A: Percentage of participants in placebo group with a RT-qPCR confirmed SARS-CoV-2 infection during the EAP with an index case participating in study R10933-10987-COV-2067 (NCT04425629)

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    End point title
    Cohort A: Percentage of participants in placebo group with a RT-qPCR confirmed SARS-CoV-2 infection during the EAP with an index case participating in study R10933-10987-COV-2067 (NCT04425629) [10]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [10] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987
    Number of subjects analysed
    186
    Units: Percentage of Participants
    number (not applicable)
        % with index case receiving R10933+R10987 in 2067
    19.8
        % with index case receiving placebo in 2067
    19.6
        % with index case treatment in 2067 not available
    10.5
    No statistical analyses for this end point

    Secondary: Cohort A: Percentage of participants with a symptomatic RT-qPCR confirmed SARS-CoV-2 infection (CDC definition) during the EAP

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    End point title
    Cohort A: Percentage of participants with a symptomatic RT-qPCR confirmed SARS-CoV-2 infection (CDC definition) during the EAP [11]
    End point description
    Symptomatic SARS-CoV-2 infection (CDC definition) is defined as a positive central lab SARS-CoV-2 RT-qPCR result (either NP, nasal or saliva) associated with signs and symptoms with the onset date occurring within 14 days of a positive RT-qPCR during the EAP. Percentage estimated by Logistic Regression.
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [11] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    752
    753
    Units: Percentage of participants
        number (not applicable)
    5.9
    0.8
    Statistical analysis title
    Cohort A: R10933 + R10987 and Placebo
    Comparison groups
    Cohort A: Placebo of R10933 + R10987 v Cohort A: R10933 + R10987
    Number of subjects included in analysis
    1505
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.12
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.051
         upper limit
    0.286

    Secondary: Cohort A: Number of weeks of symptomatic RT-qPCR-confirmed SARS-CoV-2 infection (CDC definition) during the EAP

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    End point title
    Cohort A: Number of weeks of symptomatic RT-qPCR-confirmed SARS-CoV-2 infection (CDC definition) during the EAP [12]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    752
    753
    Units: weeks
        arithmetic mean (standard deviation)
    0.21 ± 1.042
    0.01 ± 0.128
    Statistical analysis title
    Cohort A: R10933 + R10987 and Placebo
    Comparison groups
    Cohort A: R10933 + R10987 v Cohort A: Placebo of R10933 + R10987
    Number of subjects included in analysis
    1505
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Wilcoxon (Van Elteren Test)
    Confidence interval

    Secondary: Cohort A: Percentage of participants who have a symptomatic RT-qPCR confirmed SARS-CoV-2 infection (strict-term) during the EAP

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    End point title
    Cohort A: Percentage of participants who have a symptomatic RT-qPCR confirmed SARS-CoV-2 infection (strict-term) during the EAP [13]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    752
    753
    Units: Percentage of participants
        number (not applicable)
    2.8
    0.2
    Statistical analysis title
    Cohort A: R10933 + R10987 and Placebo
    Comparison groups
    Cohort A: R10933 + R10987 v Cohort A: Placebo of R10933 + R10987
    Number of subjects included in analysis
    1505
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.02
         upper limit
    0.37

    Secondary: Cohort A: Number of weeks of symptomatic RT-qPCR confirmed SARS-CoV-2 infection (strict-term) during the EAP

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    End point title
    Cohort A: Number of weeks of symptomatic RT-qPCR confirmed SARS-CoV-2 infection (strict-term) during the EAP [14]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [14] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    752
    753
    Units: weeks
        arithmetic mean (standard deviation)
    0.12 ± 0.843
    0.00 ± 0.084
    Statistical analysis title
    Cohort A: R10933 + R10987 and Placebo
    Comparison groups
    Cohort A: R10933 + R10987 v Cohort A: Placebo of R10933 + R10987
    Number of subjects included in analysis
    1505
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Wilcoxon (Van Elteren Test)
    Confidence interval

    Secondary: Cohort A: Percentage of participants who have a RT-qPCR confirmed SARS-CoV-2 infections at each week in the EAP

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    End point title
    Cohort A: Percentage of participants who have a RT-qPCR confirmed SARS-CoV-2 infections at each week in the EAP [15]
    End point description
    End point type
    Secondary
    End point timeframe
    Week 1, Week 2, Week 3, Week 4
    Notes
    [15] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    752
    753
    Units: Percentage of participants
    number (not applicable)
        Week 1
    8.9
    3.1
        Week 2
    8.5
    1.1
        Week 3
    7.7
    0.7
        Week 4
    5.6
    0.7
    No statistical analyses for this end point

    Secondary: Cohort A: Percentage of participants who have a symptomatic RT-qPCR confirmed SARS-CoV-2 infection (broad-term) at each week in the EAP

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    End point title
    Cohort A: Percentage of participants who have a symptomatic RT-qPCR confirmed SARS-CoV-2 infection (broad-term) at each week in the EAP [16]
    End point description
    End point type
    Secondary
    End point timeframe
    Week 1, Week 2, Week 3, Week 4
    Notes
    [16] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    752
    753
    Units: Percentage of participants
    number (not applicable)
        Week 1
    5.2
    1.2
        Week 2
    4.8
    0.4
        Week 3
    3.3
    0.0
        Week 4
    2.1
    0.1
    No statistical analyses for this end point

    Secondary: Cohort A: Time-weighted average of viral load from the first positive SARS CoV-2 RT-qPCR in NP swab samples (that has an onset during the EAP) until the third weekly visit after the first positive test during the EAP

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    End point title
    Cohort A: Time-weighted average of viral load from the first positive SARS CoV-2 RT-qPCR in NP swab samples (that has an onset during the EAP) until the third weekly visit after the first positive test during the EAP [17]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [17] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    107
    36
    Units: log10 copies/mL
        least squares mean (standard error)
    3.065 ± 0.243
    0.942 ± 0.317
    Statistical analysis title
    Cohort A: R10933 + R10987 and Placebo
    Comparison groups
    Cohort A: R10933 + R10987 v Cohort A: Placebo of R10933 + R10987
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    ANOVA
    Parameter type
    Difference of LS Means
    Point estimate
    -2.123
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.707
         upper limit
    -1.539
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.295

    Secondary: Cohort A: Time-weighted average of viral load from the first positive SARS-CoV-2 RT-qPCR in NP swab samples (that has an onset during the EAP) until the second weekly visit after the first positive test during the EAP

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    End point title
    Cohort A: Time-weighted average of viral load from the first positive SARS-CoV-2 RT-qPCR in NP swab samples (that has an onset during the EAP) until the second weekly visit after the first positive test during the EAP [18]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [18] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    107
    36
    Units: log10 copies/mL
        least squares mean (standard error)
    3.689 ± 0.281
    1.205 ± 0.368
    Statistical analysis title
    Cohort A: R10933 + R10987 and Placebo
    Comparison groups
    Cohort A: Placebo of R10933 + R10987 v Cohort A: R10933 + R10987
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    ANOVA
    Parameter type
    Difference of LS Means
    Point estimate
    -2.483
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.161
         upper limit
    -1.806
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.342

    Secondary: Cohort A: Maximum SARS-CoV-2 RT-qPCR viral load in NP swab samples among individuals with ≥1 RT-qPCR positive that has an onset during the EAP

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    End point title
    Cohort A: Maximum SARS-CoV-2 RT-qPCR viral load in NP swab samples among individuals with ≥1 RT-qPCR positive that has an onset during the EAP [19]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [19] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    107
    36
    Units: log10 copies/mL
        least squares mean (standard error)
    6.133 ± 0.301
    3.705 ± 0.402
    Statistical analysis title
    Cohort A: R10933 + R10987 and Placebo
    Comparison groups
    Cohort A: Placebo of R10933 + R10987 v Cohort A: R10933 + R10987
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    ANOVA
    Parameter type
    Difference of LS Mean
    Point estimate
    -2.428
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.196
         upper limit
    -1.659
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.389

    Secondary: Cohort A: SARS-CoV-2 RT-qPCR viral load in NP swab samples corresponding to the onset of first positive RT-qPCR during the EAP

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    End point title
    Cohort A: SARS-CoV-2 RT-qPCR viral load in NP swab samples corresponding to the onset of first positive RT-qPCR during the EAP [20]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [20] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    107
    36
    Units: log10 copies/mL
        least squares mean (standard error)
    6.141 ± 0.305
    3.700 ± 0.396
    Statistical analysis title
    Cohort A: R10933 + R10987 and Placebo
    Comparison groups
    Cohort A: Placebo of R10933 + R10987 v Cohort A: R10933 + R10987
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    ANOVA
    Parameter type
    Difference of LS Mean
    Point estimate
    -2.441
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.194
         upper limit
    -1.688
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.381

    Secondary: Cohort A: Area under the curve (AUC) in viral load from the first positive SARS-CoV-2 RT-qPCR NP swab samples detected during the EAP until the first confirmed negative test

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    End point title
    Cohort A: Area under the curve (AUC) in viral load from the first positive SARS-CoV-2 RT-qPCR NP swab samples detected during the EAP until the first confirmed negative test [21]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 8 months
    Notes
    [21] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    81
    33
    Units: log10 copies/mL
        arithmetic mean (standard deviation)
    65.982 ± 47.6933
    19.700 ± 14.8257
    No statistical analyses for this end point

    Secondary: Cohort A: Total Number of medically attended visits in emergency rooms or urgent care centers related to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP

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    End point title
    Cohort A: Total Number of medically attended visits in emergency rooms or urgent care centers related to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP [22]
    End point description
    Medically attended visits referred to hospitalizations, Emergency Room visits, or visits at an Urgent Care center.
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [22] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    752
    753
    Units: medically attended visits
    9
    0
    No statistical analyses for this end point

    Secondary: Cohort A: Percentage of participants with at least 1 COVID-19-related hospitalization or emergency room visit associated with a positive RT-qPCR during the EAP or all-cause death

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    End point title
    Cohort A: Percentage of participants with at least 1 COVID-19-related hospitalization or emergency room visit associated with a positive RT-qPCR during the EAP or all-cause death [23]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [23] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    752
    753
    Units: Percentage of Participants
        number (not applicable)
    0.5
    0.0
    Statistical analysis title
    Cohort A: R10933 + R10987 and Placebo
    Statistical analysis description
    Testing if there is an association between the observed results and treatment received
    Comparison groups
    Cohort A: Placebo of R10933 + R10987 v Cohort A: R10933 + R10987
    Number of subjects included in analysis
    1505
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.0621
    Method
    Fisher exact
    Confidence interval

    Secondary: Cohort A: Percentage of participants requiring medically attended visits in emergency rooms or urgent care centers related to a RT-qPCR confirmed SARS CoV-2 infection that has an onset during the EAP

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    End point title
    Cohort A: Percentage of participants requiring medically attended visits in emergency rooms or urgent care centers related to a RT-qPCR confirmed SARS CoV-2 infection that has an onset during the EAP [24]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [24] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    752
    753
    Units: Percentage of participants
        number (not applicable)
    1.1
    0.0
    Statistical analysis title
    Cohort A: R10933 + R10987 and Placebo
    Statistical analysis description
    Testing if there is an association between the observed results and treatment received’
    Comparison groups
    Cohort A: Placebo of R10933 + R10987 v Cohort A: R10933 + R10987
    Number of subjects included in analysis
    1505
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.0038
    Method
    Fisher exact
    Confidence interval

    Secondary: Cohort A: Percentage of participants hospitalized related to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP

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    End point title
    Cohort A: Percentage of participants hospitalized related to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP [25]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 8 months
    Notes
    [25] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    752
    753
    Units: Percentage of participants
        number (not applicable)
    0.1
    0.0
    No statistical analyses for this end point

    Secondary: Cohort A: Number of days of hospital and intensive care unit (ICU) stay in participants hospitalized for a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP

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    End point title
    Cohort A: Number of days of hospital and intensive care unit (ICU) stay in participants hospitalized for a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP [26]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 8 months
    Notes
    [26] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    752
    753
    Units: Days
        arithmetic mean (standard deviation)
    0.01 ± 0.401
    0.00 ± 0.000
    Statistical analysis title
    Cohort A: R10933 + R10987 and Placebo
    Comparison groups
    Cohort A: Placebo of R10933 + R10987 v Cohort A: R10933 + R10987
    Number of subjects included in analysis
    1505
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.363
    Method
    Wilcoxon (Rank Sum)
    Confidence interval

    Secondary: Cohort A: Number of days missed for daily responsibilities due to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP

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    End point title
    Cohort A: Number of days missed for daily responsibilities due to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP [27]
    End point description
    Daily responsibilities including work (employed adults) or school (students), daycare or family obligations/responsibilities (childcare or eldercare)
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [27] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    752
    753
    Units: days
        arithmetic mean (standard deviation)
    0.98 ± 4.659
    0.15 ± 1.276
    Statistical analysis title
    Cohort A: R10933 + R10987 and Placebo
    Comparison groups
    Cohort A: Placebo of R10933 + R10987 v Cohort A: R10933 + R10987
    Number of subjects included in analysis
    1505
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Wilcoxon (Van Elteren Test)
    Confidence interval

    Secondary: Cohort A: Proportion of baseline seropositive participants (based on central lab test) with TEAEs and severity of TEAEs

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    End point title
    Cohort A: Proportion of baseline seropositive participants (based on central lab test) with TEAEs and severity of TEAEs [28]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 8 months
    Notes
    [28] - 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: This endpoint is only applicable to participants in Cohort A
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987
    Number of subjects analysed
    296
    337
    Units: participants
        with at least one TEAE
    79
    83
        with at least one serious TEAE
    5
    6
    No statistical analyses for this end point

    Secondary: Cohort A and Cohort B: Incidence and Severity of symptomatic SARS-CoV-2 infections during the EAP

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    End point title
    Cohort A and Cohort B: Incidence and Severity of symptomatic SARS-CoV-2 infections during the EAP [29]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to Day 29
    Notes
    [29] - 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: This endpoint is only applicable to participants in Cohort A and Cohort B.
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987 Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    1428
    1439
    170
    165
    Units: subjects
        Total Symptomatic COVID-19
    81
    15
    57
    35
        Grade 1 Symptomatic COVID-19
    68
    11
    43
    33
        Grade 2 Symptomatic COVID-19
    11
    4
    12
    2
        Grade 3 Symptomatic COVID-19
    2
    0
    2
    0
        Grade 4 Symptomatic COVID-19
    0
    0
    0
    0
        Grade 5 Symptomatic COVID-19
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Cohort A and Cohort B: Incidence and Severity of symptomatic SARS-CoV-2 infections during the Follow-Up Period

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    End point title
    Cohort A and Cohort B: Incidence and Severity of symptomatic SARS-CoV-2 infections during the Follow-Up Period [30]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to Day 225
    Notes
    [30] - 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: This endpoint is only applicable to participants in Cohort A and Cohort B.
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987 Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    1428
    1439
    170
    165
    Units: Subjects
        Total Symptomatic COVID-19
    68
    14
    1
    1
        Grade 1 Symptomatic COVID-19
    50
    12
    1
    1
        Grade 2 Symptomatic COVID-19
    14
    2
    0
    0
        Grade 3 Symptomatic COVID-19
    4
    0
    0
    0
        Grade 4 Symptomatic COVID-19
    0
    0
    0
    0
        Grade 5 Symptomatic COVID-19
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Cohort A and Cohort B: Incidence and Severity of symptomatic SARS-CoV-2 infections in Seronegative subjects during the EAP

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    End point title
    Cohort A and Cohort B: Incidence and Severity of symptomatic SARS-CoV-2 infections in Seronegative subjects during the EAP [31]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to Day 29
    Notes
    [31] - 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: This endpoint is only applicable to participants in Cohort A and Cohort B.
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987 Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    1067
    1028
    114
    109
    Units: Subjects
        Total Symptomatic COVID-19
    74
    12
    47
    32
        Grade 1 Symptomatic COVID-19
    64
    9
    35
    30
        Grade 2 Symptomatic COVID-19
    9
    3
    10
    2
        Grade 3 Symptomatic COVID-19
    1
    0
    2
    0
        Grade 4 Symptomatic COVID-19
    0
    0
    0
    0
        Grade 5 Symptomatic COVID-19
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Cohort A and Cohort B: Incidence and Severity of symptomatic SARS-CoV-2 infections in Seronegative subjects during the Follow-Up Period

    Close Top of page
    End point title
    Cohort A and Cohort B: Incidence and Severity of symptomatic SARS-CoV-2 infections in Seronegative subjects during the Follow-Up Period [32]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to Day 226
    Notes
    [32] - 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: This endpoint is only applicable to participants in Cohort A and Cohort B.
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987 Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    1067
    1028
    114
    109
    Units: subjects
        Total Symptomatic COVID-19
    64
    10
    1
    1
        Grade 1 Symptomatic COVID-19
    47
    8
    1
    1
        Grade 2 Symptomatic COVID-19
    14
    2
    0
    0
        Grade 3 Symptomatic COVID-19
    3
    0
    0
    0
        Grade 4 Symptomatic COVID-19
    0
    0
    0
    0
        Grade 5 Symptomatic COVID-19
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Cohort A and Cohort B: Incidence and Severity of symptomatic SARS-CoV-2 infections in Seropositive subjects during the EAP

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    End point title
    Cohort A and Cohort B: Incidence and Severity of symptomatic SARS-CoV-2 infections in Seropositive subjects during the EAP [33]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to Day 29
    Notes
    [33] - 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: This endpoint is only applicable to participants in Cohort A and Cohort B.
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987 Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    296
    337
    43
    48
    Units: subjects
        Total Symptomatic COVID-19
    6
    3
    6
    3
        Grade 1 Symptomatic COVID-19
    3
    2
    5
    3
        Grade 2 Symptomatic COVID-19
    2
    1
    1
    0
        Grade 3 Symptomatic COVID-19
    1
    0
    0
    0
        Grade 4 Symptomatic COVID-19
    0
    0
    0
    0
        Grade 5 Symptomatic COVID-19
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Cohort A and Cohort B: Incidence and Severity of symptomatic SARS-CoV-2 infections in Seropositive subjects during the Follow-Up Period

    Close Top of page
    End point title
    Cohort A and Cohort B: Incidence and Severity of symptomatic SARS-CoV-2 infections in Seropositive subjects during the Follow-Up Period [34]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to Day 225
    Notes
    [34] - 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: This endpoint is only applicable to participants in Cohort A and Cohort B.
    End point values
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933 + R10987 Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    296
    337
    43
    48
    Units: Subjects
        Total Symptomatic COVID-19
    3
    3
    0
    0
        Grade 1 Symptomatic COVID-19
    3
    3
    0
    0
        Grade 2 Symptomatic COVID-19
    0
    0
    0
    0
        Grade 3Symptomatic COVID-19
    0
    0
    0
    0
        Grade 4 Symptomatic COVID-19
    0
    0
    0
    0
        Grade 5 Symptomatic COVID-19
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Cohort B: Number of weeks of symptomatic SARS-CoV-2 infection (broad-term) within 14 days of a positive RT-qPCR at baseline or during the EAP

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    End point title
    Cohort B: Number of weeks of symptomatic SARS-CoV-2 infection (broad-term) within 14 days of a positive RT-qPCR at baseline or during the EAP [35]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 8 months
    Notes
    [35] - 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: This endpoint is only applicable to participants in Cohort B
    End point values
    Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    104
    100
    Units: weeks
        arithmetic mean (standard deviation)
    1.64 ± 3.493
    0.90 ± 2.586
    Statistical analysis title
    Cohort B: Placebo of R10933 + R10987 and Placebo
    Comparison groups
    Cohort B: Placebo of R10933 + R10987 v Cohort B: R10933 + R10987
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0273
    Method
    Wilcoxon (Van Elteren Test)
    Confidence interval

    Secondary: Cohort B: Percentage of participants with Asymptomatic Infection who develop signs and symptoms (CDC definition) within 14 days of a positive RT-qPCR at baseline or during the EAP

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    End point title
    Cohort B: Percentage of participants with Asymptomatic Infection who develop signs and symptoms (CDC definition) within 14 days of a positive RT-qPCR at baseline or during the EAP [36]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [36] - 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: This endpoint is only applicable to participants in Cohort B
    End point values
    Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    104
    100
    Units: percentage of participants
        number (not applicable)
    39.7
    26.3
    Statistical analysis title
    Cohort B: Placebo of R10933 + R10987 and Placebo
    Comparison groups
    Cohort B: Placebo of R10933 + R10987 v Cohort B: R10933 + R10987
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.046
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.54
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.299
         upper limit
    0.989

    Secondary: Cohort B: Percentage of participants who subsequently develop signs and symptoms (strict-term) within 14 days of a positive RT-qPCR at baseline or during the EAP

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    End point title
    Cohort B: Percentage of participants who subsequently develop signs and symptoms (strict-term) within 14 days of a positive RT-qPCR at baseline or during the EAP [37]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [37] - 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: This endpoint is only applicable to participants in Cohort B
    End point values
    Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    104
    100
    Units: Percentage of Participants
        number (not applicable)
    18.5
    9.7
    Statistical analysis title
    Cohort B: R10933 + R10987 and Placebo
    Comparison groups
    Cohort B: Placebo of R10933 + R10987 v Cohort B: R10933 + R10987
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0721
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.47
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.207
         upper limit
    1.07

    Secondary: Cohort B: Number of weeks of symptomatic SARS-CoV-2 infection (CDC definition) within 14 days of a positive RT-qPCR at baseline or during the EAP

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    End point title
    Cohort B: Number of weeks of symptomatic SARS-CoV-2 infection (CDC definition) within 14 days of a positive RT-qPCR at baseline or during the EAP [38]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 8 months
    Notes
    [38] - 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: This endpoint is only applicable to participants in Cohort B
    End point values
    Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    104
    100
    Units: weeks
        arithmetic mean (standard deviation)
    1.71 ± 3.569
    0.88 ± 2.584
    Statistical analysis title
    Cohort B: Placebo of R10933 + R10987 and Placebo
    Comparison groups
    Cohort B: Placebo of R10933 + R10987 v Cohort B: R10933 + R10987
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.026
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Cohort B: Number of weeks of symptomatic SARS-CoV-2 infection (Strict-term definition) within 14 days of a positive RT-qPCR at baseline or during the EAP

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    End point title
    Cohort B: Number of weeks of symptomatic SARS-CoV-2 infection (Strict-term definition) within 14 days of a positive RT-qPCR at baseline or during the EAP [39]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 8 months
    Notes
    [39] - 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: This endpoint is only applicable to participants in Cohort B
    End point values
    Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    104
    100
    Units: weeks
        arithmetic mean (standard deviation)
    0.68 ± 1.889
    0.40 ± 1.876
    Statistical analysis title
    Cohort B: Placebo of R10933 + R10987 and Placebo
    Comparison groups
    Cohort B: Placebo of R10933 + R10987 v Cohort B: R10933 + R10987
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0614
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Cohort B: Change in viral load from baseline to day 8 visit in NP swab samples

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    End point title
    Cohort B: Change in viral load from baseline to day 8 visit in NP swab samples [40]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to day 8 visit
    Notes
    [40] - 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: This endpoint is only applicable to participants in Cohort B.
    End point values
    Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    97
    95
    Units: log10 copies/mL
        least squares mean (standard error)
    -1.543 ± 0.238
    -3.004 ± 0.239
    Statistical analysis title
    Cohort B: Placebo of R10933 + R10987 and Placebo
    Comparison groups
    Cohort B: Placebo of R10933 + R10987 v Cohort B: R10933 + R10987
    Number of subjects included in analysis
    192
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    ANCOVA
    Parameter type
    LS mean difference
    Point estimate
    -1.461
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.127
         upper limit
    -0.795
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.337

    Secondary: Cohort B: Change in viral load from baseline to day 15 visit in NP swab samples

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    End point title
    Cohort B: Change in viral load from baseline to day 15 visit in NP swab samples [41]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to day 15 visit
    Notes
    [41] - 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: This endpoint is only applicable to participants in Cohort B.
    End point values
    Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    97
    95
    Units: log10 copies/mL
        least squares mean (standard error)
    -4.014 ± 0.195
    -4.864 ± 0.199
    Statistical analysis title
    Cohort B: Placebo of R10933 + R10987 and Placebo
    Comparison groups
    Cohort B: Placebo of R10933 + R10987 v Cohort B: R10933 + R10987
    Number of subjects included in analysis
    192
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0026
    Method
    ANCOVA
    Parameter type
    LS mean difference
    Point estimate
    -0.85
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.4
         upper limit
    -0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.279

    Secondary: Cohort B: Time-weighted average change from baseline in viral load (log10 copies/mL) in NP swab samples until the day 22 visit

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    End point title
    Cohort B: Time-weighted average change from baseline in viral load (log10 copies/mL) in NP swab samples until the day 22 visit [42]
    End point description
    End point type
    Secondary
    End point timeframe
    Day 22
    Notes
    [42] - 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: This endpoint is only applicable to participants in Cohort B
    End point values
    Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    96
    95
    Units: log10 copies/mL
        least squares mean (standard error)
    -2.639 ± 0.136
    -3.580 ± 0.137
    Statistical analysis title
    Cohort B: Placebo of R10933 + R10987 and Placebo
    Comparison groups
    Cohort B: Placebo of R10933 + R10987 v Cohort B: R10933 + R10987
    Number of subjects included in analysis
    191
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    ANCOVA
    Parameter type
    LS mean difference
    Point estimate
    -0.94
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.321
         upper limit
    -0.559
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.193

    Secondary: Cohort B: AUC in viral load from the first positive SARS-CoV-2 RT-qPCR NP swab samples detected during the EAP to the first confirmed negative test

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    End point title
    Cohort B: AUC in viral load from the first positive SARS-CoV-2 RT-qPCR NP swab samples detected during the EAP to the first confirmed negative test [43]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 8 months
    Notes
    [43] - 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: This endpoint is only applicable to participants in Cohort B
    End point values
    Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    101
    98
    Units: log10 copies/mL
        least squares mean (standard error)
    82.008 ± 4.328
    55.964 ± 4.201
    Statistical analysis title
    Cohort B: R10933 + R10987 and Placebo
    Comparison groups
    Cohort B: Placebo of R10933 + R10987 v Cohort B: R10933 + R10987
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    ANCOVA
    Parameter type
    Difference of LS Mean
    Point estimate
    -26.045
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -37.973
         upper limit
    -14.117
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.041

    Secondary: Cohort B: Maximum SARS-CoV-2 RT-qPCR viral load in NP swab samples in participants with 1 or more positive test that has an onset during the EAP

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    End point title
    Cohort B: Maximum SARS-CoV-2 RT-qPCR viral load in NP swab samples in participants with 1 or more positive test that has an onset during the EAP [44]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 8 months
    Notes
    [44] - 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: This endpoint is only applicable to participants in Cohort B
    End point values
    Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    101
    98
    Units: log10 copies/mL
        least squares mean (standard error)
    4.731 ± 0.238
    3.336 ± 0.240
    Statistical analysis title
    Cohort B: R10933 + R10987 and Placebo
    Comparison groups
    Cohort B: Placebo of R10933 + R10987 v Cohort B: R10933 + R10987
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    ANCOVA
    Parameter type
    Difference of LS Mean
    Point estimate
    -1.395
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.063
         upper limit
    -0.727
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.338

    Secondary: Cohort B: Number of medically attended visits in emergency rooms or urgent care centers related to RT-qPCR confirmed SARS-CoV-2 infection that has an onset at baseline or during the EAP

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    End point title
    Cohort B: Number of medically attended visits in emergency rooms or urgent care centers related to RT-qPCR confirmed SARS-CoV-2 infection that has an onset at baseline or during the EAP [45]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [45] - 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: This endpoint is only applicable to participants in Cohort B
    End point values
    Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    104
    100
    Units: Medically attended visits
        arithmetic mean (standard deviation)
    0.06 ± 0.234
    0.00 ± 0.000
    Statistical analysis title
    Cohort B: Placebo of R10933 + R10987 and Placebo
    Comparison groups
    Cohort B: Placebo of R10933 + R10987 v Cohort B: R10933 + R10987
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0138
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Cohort B: Percentage of participants requiring medically attended visits in emergency rooms or urgent care centers related to a RT-qPCR confirmed SARS CoV-2 infection that has an onset at baseline or during the EAP

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    End point title
    Cohort B: Percentage of participants requiring medically attended visits in emergency rooms or urgent care centers related to a RT-qPCR confirmed SARS CoV-2 infection that has an onset at baseline or during the EAP [46]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [46] - 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: This endpoint is only applicable to participants in Cohort B
    End point values
    Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    104
    100
    Units: Percentage of participants
        number (not applicable)
    5.8
    0.0
    Statistical analysis title
    Cohort B: Placebo of R10933 + R10987 and Placebo
    Statistical analysis description
    Testing if there is an association between the observed results and treatment received
    Comparison groups
    Cohort B: Placebo of R10933 + R10987 v Cohort B: R10933 + R10987
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.0292
    Method
    Fisher exact
    Confidence interval

    Secondary: Cohort B: Percentage of participants hospitalized related to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset at baseline or during the EAP

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    End point title
    Cohort B: Percentage of participants hospitalized related to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset at baseline or during the EAP [47]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 8 months
    Notes
    [47] - 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: This endpoint is only applicable to participants in Cohort B
    End point values
    Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    104
    100
    Units: Percentage of participants
        number (not applicable)
    2.9
    0.0
    Statistical analysis title
    Cohort B: Placebo of R10933 + R10987 and Placebo
    Statistical analysis description
    Testing if there is an association between the observed results and treatment received
    Comparison groups
    Cohort B: R10933 + R10987 v Cohort B: Placebo of R10933 + R10987
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.2466
    Method
    Fisher exact
    Confidence interval

    Secondary: Cohort B: Number of days missed for daily responsibilities (where applicable) due to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset at baseline or during the EAP

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    End point title
    Cohort B: Number of days missed for daily responsibilities (where applicable) due to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset at baseline or during the EAP [48]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 1 month
    Notes
    [48] - 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: This endpoint is only applicable to participants in Cohort B
    End point values
    Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    104
    100
    Units: Days
        arithmetic mean (standard deviation)
    5.69 ± 8.802
    5.18 ± 8.940
    Statistical analysis title
    Cohort B: Placebo of R10933 + R10987 and Placebo
    Comparison groups
    Cohort B: Placebo of R10933 + R10987 v Cohort B: R10933 + R10987
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7861
    Method
    Wilcoxon (Van Elteren Test)
    Confidence interval

    Secondary: Cohort B: Number of days of hospital and intensive care unit (ICU) stay in participants hospitalized for a RT-qPCR confirmed SARS-CoV-2 infection that has an onset at baseline or during the EAP

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    End point title
    Cohort B: Number of days of hospital and intensive care unit (ICU) stay in participants hospitalized for a RT-qPCR confirmed SARS-CoV-2 infection that has an onset at baseline or during the EAP [49]
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 8 months
    Notes
    [49] - 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: This endpoint is only applicable to participants in Cohort B
    End point values
    Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987
    Number of subjects analysed
    104
    100
    Units: days
        arithmetic mean (standard deviation)
    0.38 ± 2.671
    0.00 ± 0.000
    Statistical analysis title
    Cohort B: R10933 + R10987 and Placebo
    Comparison groups
    Cohort B: Placebo of R10933 + R10987 v Cohort B: R10933 + R10987
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0842
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Concentrations of REGN10933 in serum over time

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    End point title
    Concentrations of REGN10933 in serum over time
    End point description
    End point type
    Secondary
    End point timeframe
    0 Days Post-Dose, 28 Days Post-Dose, 56 Days Post-Dose, 112 Days Post-Dose, 168 Days Post-Dose, 224 Days Post-Dose
    End point values
    PKAS Analysis Set
    Number of subjects analysed
    170
    Units: milligrams per liter (mg/L)
    arithmetic mean (standard deviation)
        0 Days Post-Dose (n=133)
    0.613 ± 3.97
        28 Days Post-Dose (n=122)
    28.7 ± 14.5
        56 Days Post-Dose (n=140)
    14.3 ± 8.22
        112 Days Post-Dose (n=113)
    4.29 ± 7.74
        168 Days Post-Dose (n=132)
    1.45 ± 3.34
        224 Days Post-Dose (n=139)
    0.498 ± 1.01
    No statistical analyses for this end point

    Secondary: Concentrations of REGN10987 in serum over time

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    End point title
    Concentrations of REGN10987 in serum over time
    End point description
    End point type
    Secondary
    End point timeframe
    0 Days Post-Dose, 28 Days Post-Dose, 56 Days Post-Dose, 112 Days Post-Dose, 168 Days Post-Dose, 224 Days Post-Dose
    End point values
    Anti-drug Antibodies Analysis Set (AAS)
    Number of subjects analysed
    170
    Units: mg/L
    arithmetic mean (standard deviation)
        0 Days Post-Dose (n=133)
    0.601 ± 4.18
        28 Days Post-Dose (n=122)
    23.4 ± 11.8
        56 Days Post-Dose (n=140)
    10.2 ± 6.53
        112 Days Post-Dose (n=113)
    2.65 ± 6.17
        168 Days Post-Dose (n=132)
    0.768 ± 2.40
        224 Days Post-Dose (n=139)
    0.198 ± 0.617
    No statistical analyses for this end point

    Secondary: Immunogenicity as measured by anti-drug antibodies (ADAs) to REGN10933

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    End point title
    Immunogenicity as measured by anti-drug antibodies (ADAs) to REGN10933
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 8 months
    End point values
    Anti-drug Antibodies Analysis Set (AAS)
    Number of subjects analysed
    3201
    Units: participants
        Negative
    2863
        Pre-Existing Immunoreactivity
    84
        Treatment Boosted Response
    1
        Treatment Emergent Response
    253
    No statistical analyses for this end point

    Secondary: Immunogenicity as measured by anti-drug antibodies (ADAs) to REGN10987

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    End point title
    Immunogenicity as measured by anti-drug antibodies (ADAs) to REGN10987
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 8 months
    End point values
    Anti-drug Antibodies Analysis Set (AAS)
    Number of subjects analysed
    3201
    Units: participants
        Negative
    2751
        Pre-Existing Immunoreactivity
    105
        Treatment Boosted Response
    9
        Treatment Emergent Response
    336
    No statistical analyses for this end point

    Secondary: Immunogenicity as Measured by Neutralizing Anti-drug Antibody (NAb) to REGN10933

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    End point title
    Immunogenicity as Measured by Neutralizing Anti-drug Antibody (NAb) to REGN10933
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 8 months
    End point values
    NAb Analysis Set
    Number of subjects analysed
    3199
    Units: participants
        ADA Negative
    2863
        Pre-existing immunoreactivity; Negative NAb-
    79
        Pre-existing immunoreactivity; NAb+
    5
        Treatment-emergent & Treatment-boosted; NAb-
    215
        Treatment-emergent & Treatment-boosted; NAb+
    37
    No statistical analyses for this end point

    Secondary: Immunogenicity as Measured by Neutralizing Anti-drug Antibody (NAb) to REGN10987

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    End point title
    Immunogenicity as Measured by Neutralizing Anti-drug Antibody (NAb) to REGN10987
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 8 months
    End point values
    NAb Analysis Set
    Number of subjects analysed
    3199
    Units: participants
        ADA Negative
    2751
        Pre-Existing Immunoreactivity; NAb-
    39
        Pre-Existing Immunoreactivity; NAb+
    66
        Treatment-emergent & Treatment-boosted; NAb-
    156
        Treatment-emergent & Treatment-boosted; NAb+
    187
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to Day 226
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    Cohort A: Placebo of R10933 + R10987
    Reporting group description
    Placebo of R10933 + R10987 Adult and Adolescent Subjects (≥12years) Who Are SARS-CoV-2 RT-qPCR negative at baseline

    Reporting group title
    Cohort A: R10933+R10987
    Reporting group description
    Cohort A: R10933+R10987 Adult and Adolescent Subjects (≥12years) who are SARS-CoV-2 RT-qPCR negative at baseline

    Reporting group title
    Cohort A1: Placebo of R10933 + R10987
    Reporting group description
    Placebo of R10933 + R10987 Pediatric Subjects (<12 years) with SARS-CoV-2 RT-qPCR Negative at baseline

    Reporting group title
    Cohort B: Placebo of R10933 + R10987
    Reporting group description
    Cohort B: Placebo of R10933 + R10987 Adult and Adolescent Subjects (≥12years) Who Are SARS-CoV-2 RT-qPCR Positive at baseline

    Reporting group title
    Cohort B: R10933 + R10987
    Reporting group description
    Cohort B: R10933 + R10987 Adult and Adolescent Subjects (≥12years) Who Are SARS-CoV-2 RT-qPCR Positive at baseline

    Reporting group title
    Undetermined: Placebo of R10933 + R10987
    Reporting group description
    Undetermined: Placebo of R10933 + R10987 Adult and Adolescent subjects (≥12 years) whose baseline RT-qPCR status was inconclusive or missing

    Reporting group title
    Undetermined: R10933 + R10987
    Reporting group description
    Undetermined: R10933 + R10987 Adult and Adolescent subjects (≥12 years) whose baseline RT-qPCR status was inconclusive or missing

    Serious adverse events
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933+R10987 Cohort A1: Placebo of R10933 + R10987 Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987 Undetermined: Placebo of R10933 + R10987 Undetermined: R10933 + R10987
    Total subjects affected by serious adverse events
         subjects affected / exposed
    23 / 1428 (1.61%)
    24 / 1439 (1.67%)
    0 / 1 (0.00%)
    5 / 170 (2.94%)
    1 / 165 (0.61%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         number of deaths (all causes)
    2
    3
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Vascular disorders
    Essential hypertension
         subjects affected / exposed
    1 / 1428 (0.07%)
    0 / 1439 (0.00%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive urgency
         subjects affected / exposed
    1 / 1428 (0.07%)
    0 / 1439 (0.00%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Invasive ductal breast carcinoma
         subjects affected / exposed
    1 / 1428 (0.07%)
    0 / 1439 (0.00%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervix carcinoma recurrent
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    2 / 1428 (0.14%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pre-eclampsia
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicidal ideation
         subjects affected / exposed
    2 / 1428 (0.14%)
    0 / 1439 (0.00%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mania
         subjects affected / exposed
    1 / 1428 (0.07%)
    0 / 1439 (0.00%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Schizophrenia
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Breast haematoma
         subjects affected / exposed
    1 / 1428 (0.07%)
    0 / 1439 (0.00%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Gun shot wound
         subjects affected / exposed
    1 / 1428 (0.07%)
    0 / 1439 (0.00%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 1428 (0.07%)
    0 / 1439 (0.00%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Soft tissue injury
         subjects affected / exposed
    1 / 1428 (0.07%)
    0 / 1439 (0.00%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Burns second degree
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural complication
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural inflammation
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 1428 (0.00%)
    2 / 1439 (0.14%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    1 / 165 (0.61%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic lung injury
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    1 / 1428 (0.07%)
    0 / 1439 (0.00%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 1428 (0.00%)
    2 / 1439 (0.14%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral infarction
         subjects affected / exposed
    1 / 1428 (0.07%)
    0 / 1439 (0.00%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 1428 (0.00%)
    0 / 1439 (0.00%)
    0 / 1 (0.00%)
    1 / 170 (0.59%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 1428 (0.07%)
    0 / 1439 (0.00%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Diabetic foot
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    5 / 1428 (0.35%)
    0 / 1439 (0.00%)
    0 / 1 (0.00%)
    2 / 170 (1.18%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    3 / 1428 (0.21%)
    0 / 1439 (0.00%)
    0 / 1 (0.00%)
    2 / 170 (1.18%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    2 / 1428 (0.14%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 1428 (0.07%)
    2 / 1439 (0.14%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 1428 (0.07%)
    0 / 1439 (0.00%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scrotal abscess
         subjects affected / exposed
    1 / 1428 (0.07%)
    0 / 1439 (0.00%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 1428 (0.07%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    0 / 1428 (0.00%)
    1 / 1439 (0.07%)
    0 / 1 (0.00%)
    0 / 170 (0.00%)
    0 / 165 (0.00%)
    0 / 44 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Cohort A: Placebo of R10933 + R10987 Cohort A: R10933+R10987 Cohort A1: Placebo of R10933 + R10987 Cohort B: Placebo of R10933 + R10987 Cohort B: R10933 + R10987 Undetermined: Placebo of R10933 + R10987 Undetermined: R10933 + R10987
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    247 / 1428 (17.30%)
    96 / 1439 (6.67%)
    0 / 1 (0.00%)
    63 / 170 (37.06%)
    41 / 165 (24.85%)
    10 / 44 (22.73%)
    2 / 23 (8.70%)
    Infections and infestations
    COVID-19
         subjects affected / exposed
    148 / 1428 (10.36%)
    29 / 1439 (2.02%)
    0 / 1 (0.00%)
    58 / 170 (34.12%)
    35 / 165 (21.21%)
    4 / 44 (9.09%)
    1 / 23 (4.35%)
         occurrences all number
    149
    32
    0
    59
    35
    4
    1
    Asymptomatic COVID-19
         subjects affected / exposed
    119 / 1428 (8.33%)
    71 / 1439 (4.93%)
    0 / 1 (0.00%)
    6 / 170 (3.53%)
    7 / 165 (4.24%)
    7 / 44 (15.91%)
    1 / 23 (4.35%)
         occurrences all number
    119
    73
    0
    6
    7
    7
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Jul 2020
    Amendment 1: The purpose of this amendment is to change the collection of respiratory samples for SARS-CoV-2 reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) from nasal swabs and saliva samples to nasopharyngeal (NP) swab samples due to analysis of data from baseline samples from the REGN10933+REGN10987 treatment studies, where study patients were sampled by NP swabs, nasal swabs, and saliva for side-by-side comparison.
    27 Aug 2020
    Amendment 2: The primary purpose of this amendment is to remove the requirement for subjects to have at least 48 hours of sustained exposure to the index case.
    07 Oct 2020
    Amendment 3: The primary purpose of this amendment is to include adolescent subjects aged 12 years to less than 18 years in the study. The inclusion of adolescent subjects is considered relevant to the populations at risk for infection with SARS-CoV-2.
    24 Nov 2020
    Amendment 4: The primary purposes of this amendment are 1) to change from 2 primary endpoints to 1 primary endpoint, 2) to increase the sample size, 3) to allow for the inclusion of pediatric subjects aged <12 years, 4) to allow for the inclusion of women who are pregnant or breastfeeding
    19 Jan 2021
    Amendment 5: The primary purpose of this amendment is to describe the verification of the sample size assumptions used to design the study
    25 Mar 2021
    Amendment 6: The primary purpose of this amendment is to revise and add objectives and endpoints, as well as to define the statistical testing hierarchy for the primary and key secondary endpoints.

    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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