History of Changes for Study: NCT04425629

Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Adult Patients With COVID-19

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Study Record Versions

Version	Submitted Date	Changes
1	June 8, 2020	None (earliest Version on record)
2	June 24, 2020	Recruitment Status, Study Status, Contacts/Locations and Conditions
3	July 10, 2020	Outcome Measures, Study Status, Contacts/Locations, Eligibility, Conditions and Study Description
4	July 20, 2020	Outcome Measures, Study Design and Study Status
5	July 23, 2020	Contacts/Locations, Study Description and Study Status
6	August 6, 2020	Contacts/Locations and Study Status
7	August 13, 2020	Study Status, Outcome Measures, Contacts/Locations, Eligibility, Study Design and Study Identification
8	August 20, 2020	Contacts/Locations and Study Status
9	September 3, 2020	Study Status and Contacts/Locations
10	September 14, 2020	Contacts/Locations and Study Status
11	September 18, 2020	Contacts/Locations and Study Status
12	October 8, 2020	Study Status and Contacts/Locations
13	October 16, 2020	Contacts/Locations and Study Status
14	November 9, 2020	Contacts/Locations and Study Status
15	December 4, 2020	Study Status
16	December 11, 2020	Contacts/Locations, Outcome Measures, Study Status, Eligibility, Study Design, Study Description and Study Identification
17	January 7, 2021	Outcome Measures, Study Status, Eligibility, Arms and Interventions and Study Description
18	February 18, 2021	Contacts/Locations and Study Status
19	March 31, 2021	Outcome Measures, Contacts/Locations, Study Status, Eligibility, Arms and Interventions and Study Description
20	May 19, 2021	Study Status and Contacts/Locations
21	August 13, 2021	Study Status, Contacts/Locations and Arms and Interventions
22	October 1, 2021	Arms and Interventions, Study Design, Study Status and Contacts/Locations
23	February 10, 2022	Recruitment Status, Study Status, Contacts/Locations and Study Design
24	June 13, 2022	Study Status and Document Section
25	July 11, 2022	Recruitment Status and Study Status
26	July 26, 2022	Recruitment Status and Study Status
27	January 20, 2023	Quality Control Review has not concluded Returned: February 17, 2023 Outcome Measures, Study Status, Document Section
28	March 14, 2023	Quality Control Review has not concluded Returned: April 10, 2023 Outcome Measures, Study Status
29	May 3, 2023	Quality Control Review has not concluded Returned: June 1, 2023 Outcome Measures, Study Status
30	June 26, 2023	Quality Control Review has not concluded Returned: July 21, 2023 Outcome Measures, Study Status
31	August 14, 2023	Quality Control Review has not concluded Returned: September 7, 2023 Outcome Measures, Study Status
32	September 29, 2023	Quality Control Review has not concluded Returned: October 24, 2023 Outcome Measures, Study Status
33	November 9, 2023	Quality Control Review has not concluded Returned: November 29, 2023 Outcome Measures, Study Status
34	December 20, 2023	Study Status, Outcome Measures

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	R10933-10987-COV-2067
Brief Title:	Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Adult Patients With COVID-19
Official Title:	A Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Patients With COVID-19
Secondary IDs:

Study Status


Record Verification:	June 2020
Overall Status:	Not yet recruiting
Study Start:	June 9, 2020
Primary Completion:	November 21, 2020 [Anticipated]
Study Completion:	November 21, 2020 [Anticipated]

First Submitted:	June 8, 2020
First Submitted that Met QC Criteria:	June 8, 2020
First Posted:	June 11, 2020 [Actual]

Last Update Submitted that Met QC Criteria:	June 8, 2020
Last Update Posted:	June 11, 2020 [Actual]

Sponsor/Collaborators


Sponsor:	Regeneron Pharmaceuticals
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	Yes

Study Description

Brief Summary:

The primary objectives are:

Phase 1 Part A

To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo
To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral shedding of SARS-CoV-2 Phase 2
To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral shedding of SARS-CoV-2.

Phase 3

• To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo

Detailed Description:

Conditions


Conditions:	COVID-19
Keywords:	Coronavirus disease 2019 (COVID-19) Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) coronavirus

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 1/Phase 2
Interventional Study Model:	Parallel Assignment
	Phase 1/Phase 2/Phase 3
Number of Arms:	3
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:	Randomized
Enrollment:	1054 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Experimental: REGN10933+REGN10987 low dose	Drug: REGN10933+REGN10987 combination therapy Administered intravenously (IV) single dose
Experimental: REGN10933+REGN10987 high dose	Drug: REGN10933+REGN10987 combination therapy Administered intravenously (IV) single dose
Placebo Comparator: Placebo	Drug: Placebo Placebo IV Single Dose

Outcome Measures


Primary Outcome Measures:
1.	Proportion of patients with treatment-emergent serious adverse events (SAEs) [ Time Frame: Through Day 29 ] Primary: Phase 1 Secondary: Phase 2, Phase 3
2.	Proportion of patients with infusion-related reactions [ Time Frame: Through Day 4 ] Primary: Phase 1 Secondary: Phase 2, Phase 3
3.	Proportion of patients with hypersensitivity reactions [ Time Frame: Through Day 29 ] Primary: Phase 1 Secondary: Phase 2, Phase 3
4.	Time-weighted average change from baseline in viral shedding as measured by quantitative reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples [ Time Frame: Baseline up to Day 22 ] Phase 1 only
5.	Time-weighted average change from baseline in viral shedding as measured by RT-qPCR in saliva samples [ Time Frame: Baseline up to Day 22 ] Primary: Phase 2 Secondary: Phase 1, Phase 3
6.	Proportion of patients with at least one COVID-19 related medically attended visit [ Time Frame: Through Day 29 ] Primary: Phase 3 Secondary: Phase 1, Phase 2
Secondary Outcome Measures:
1.	Time-weighted average change from baseline in viral shedding measured by RT-qPCR in nasal swab samples [ Time Frame: Baseline up to Day 22 ]
2.	Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR in any tested samples [ Time Frame: Through Day 29 ]
3.	Change from baseline in Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral shedding as measured by RT-qPCR in NP swabs [ Time Frame: Baseline up to Day 29 ] Phase 1 only
4.	Change from baseline in SARS-CoV-2 viral shedding as measured by RT-qPCR in saliva samples [ Time Frame: Baseline up to Day 29 ]
5.	Change from baseline in SARS-CoV-2 viral shedding as measured by RT-qPCR in nasal swabs [ Time Frame: Baseline up to Day 29 ]
6.	Proportion of patients with at least two COVID-19 related medically attended visits [ Time Frame: Through Day 29 ]
7.	Total number of COVID-19 related medically-attended visits [ Time Frame: Through Day 29 ]
8.	Proportion of patients admitted to a hospital due to COVID-19 [ Time Frame: Through Day 29 ]
9.	Proportion of patients admitted to an intensive care unit (ICU) due to COVID-19 [ Time Frame: Through Day 29 ]
10.	Proportion of patients at least 1 outpatient or telemedicine visit due to COVID-19 [ Time Frame: Through Day 29 ]
11.	Proportion of patients requiring mechanical ventilation due to COVID-19 [ Time Frame: Through Day 29 ]
12.	Serum concentration of REGN10933 over time [ Time Frame: Through Day 29 ]
13.	Serum concentration of REGN10987 over time [ Time Frame: Through Day 29 ]
14.	Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of REGN10933 [ Time Frame: Through Day 29 ] Phase 1 only
15.	Assessment of PK parameter: maximum serum concentration observed (Cmax) of REGN10987 [ Time Frame: Through Day 29 ] Phase 1 only
16.	Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10933 [ Time Frame: Through Day 29 ] Phase 1 only
17.	Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10987 [ Time Frame: Through Day 29 ] Phase 1 only
18.	Assessment of PK parameter: Time to Cmax (tmax) for REGN10933 [ Time Frame: Through Day 29 ] Phase 1 only
19.	Assessment of PK parameter: Time to Cmax (tmax) for REGN10987 [ Time Frame: Through Day 29 ] Phase 1 only
20.	Assessment of PK parameter: Area Under the Curve (AUC) computed from time zero to the time of the last positive concentration (AUClast) for REGN10933 [ Time Frame: Through Day 29 ] Phase 1 only
21.	Assessment of PK parameter: AUC computed from time zero to the time of the last positive concentration (AUClast) for REGN10987 [ Time Frame: Through Day 29 ] Phase 1 only
22.	Incidence of anti-drug antibodies (ADA) to REGN10933 [ Time Frame: Through Day 29 ]
23.	Incidence of anti-drug antibodies (ADA) to REGN10987 [ Time Frame: Through Day 29 ]
24.	Number of days of hospitalization due to COVID-19 [ Time Frame: Through Day 29 ] Phase 2, Phase 3
25.	Number of deaths due to any cause (All-Cause Mortality) [ Time Frame: Through Day 29 ] Phase 2, Phase 3

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Key Inclusion Criteria: Has laboratory-confirmed SARS-CoV-2 infection (positive RT-PCR test) ≤72 hours of randomization Is experiencing ≥1 of the following symptoms at randomization: fever, cough, shortness of breath Has experienced COVID-19 symptoms for <7 days - Key Exclusion Criteria: Has been admitted to a hospital prior to randomization, or is hospitalized (inpatient) at randomization, due to COVID-19 Has participated, or is participating, in a clinical research study evaluating COVID-19 convalescent plasma, monoclonal antibodies against SARS-CoV-2, or intravenous immunoglobulin (IVIG) within 3 months or less than 5 half-lives of the investigational product (whichever is longer) prior to the screening visit Has a history of COVID-19 investigational or Emergency Use Authorization (EUA)-approved treatments in the past 30 days or less than 5 half-lives of the investigational product (whichever is longer) prior to the screening visit. This includes, but is not limited to: remdesivir, hydroxychloroquine, tocilizumab, sarilumab, and other immunomodulatory agents Current use of any COVID-19 investigational or EUA-approved treatment NOTE: Other Protocol defined Inclusion/Exclusion criteria apply

Contacts/Locations


Central Contact Person:	Clinical Trials Administrator Telephone: 844-734-6643 Email: clinicaltrials@regeneron.com
Study Officials:	Clinical Trial Management Study Director Regeneron Pharmaceuticals
Locations:

IPDSharing


Plan to Share IPD:	Yes All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
	Supporting Information: Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR) Analytic Code
	Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification
	Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., Food and Drug Administration (FDA), European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
	URL: https://vivli.org/

References


Links:
Available IPD/Information: