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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
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

R10933-10987-COV-2069

ISRCTN number

US NCT number

WHO universal trial number (UTN)

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

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?

Analysis stage

Final

Date of interim/final analysis

04 Oct 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

04 Oct 2021

Was the trial ended prematurely?

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

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 3075

Country: Number of subjects enrolled

Romania: 97

Country: Number of subjects enrolled

Moldova, Republic of: 126

Worldwide total number of subjects

3298

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

145

Adults (18-64 years)

2867

From 65 to 84 years

274

85 years and over

Subject disposition

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Recruitment details

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 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

Are arms mutually exclusive

Yes

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.

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

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.

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

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

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

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

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
Adverse event, serious fatal	2	3	-	-	-	-	-
Physician decision	1	2	-	2	-	2	5
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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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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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

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

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

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

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 )

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 )

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

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 )

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

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

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 )

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

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 )

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

Top of page

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 )

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

Top of page

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 )

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 )

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 )

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

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

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

Top of page

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 )

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

Top of page

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 )

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

Top of page

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

Top of page

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

Top of page

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

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 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

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

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 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

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

Top of page

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 )

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

Top of page

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

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

Top of page

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

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

Top of page

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 )

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

Top of page

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 )

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

Top of page

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 )

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

Top of page

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 )

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

Top of page

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 )

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

Top of page

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 )

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

Top of page

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 )

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

Top of page

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 )

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

Top of page

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

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

Top of page

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

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

Top of page

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 )

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

Top of page

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 )

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

Top of page

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

Top of page

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

Top of page

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

Top of page

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

Top of page

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

Top of page

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

Top of page

Timeframe for reporting adverse events

Up to Day 226

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.0

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
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
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
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
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
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
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
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
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
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

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Were there any global substantial amendments to the protocol? Yes

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.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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)

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)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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