Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for Hospitalized Adult Patients With COVID-19
A Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Hospitalized Patients With COVID-19
2 other identifiers
interventional
2,252
6 countries
123
Brief Summary
The primary objectives are: Pooled Phase 3 (Cohort 1) and Phase 2 (Cohort 1A)
- To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral load of SARS-CoV-2
- To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo, as measured by death or mechanical ventilation Phase 1/2 (Cohort 1)
- To exclude futility of REGN10933+REGN10987 compared to placebo, as measured by death or mechanical ventilation
- To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 covid19
Started Jun 2020
Typical duration for phase_1 covid19
123 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 8, 2020
CompletedStudy Start
First participant enrolled
June 10, 2020
CompletedFirst Posted
Study publicly available on registry
June 11, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 7, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
October 22, 2021
CompletedResults Posted
Study results publicly available
July 25, 2022
CompletedJanuary 27, 2023
January 1, 2023
11 months
June 8, 2020
May 5, 2022
January 25, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (12)
Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Time-weighted Average (TWA) Change in Viral Load in Nasopharyngeal (NP) Samples Based on Seronegative mFAS
Time-weighted average daily change from Day 1 to Day 7 in viral load (log10 copies/mL), as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples.
Day 1 to Day 7
Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 6 Through Day 29 Based on High Viral Load mFAS
Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on high viral load mFAS were reported.
Day 6 to Day 29
Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 6 Through Day 29 Based on Seronegative mFAS
Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on seronegative mFAS were reported.
Day 6 to Day 29
Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 6 Through Day 29 Based on Overall mFAS
Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on overall FAS were reported.
Day 6 to Day 29
Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 1 Through Day 29 Based on High Viral Load mFAS
Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on high viral load mFAS were reported.
Day 1 to Day 29
Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 1 Through Day 29 Based on Seronegative mFAS
Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on seronegative mFAS were reported.
Day 1 to Day 29
Pooled Analysis (Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]): Percentage of Participants Who Died or Went on Mechanical Ventilation From Day 1 Through Day 29 Based on Overall mFAS
Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on overall mFAS were reported.
Day 1 to Day 29
Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Treatment-Emergent Serious Adverse Events
Treatment-emergent adverse events are defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the observation period.
Up to Day 169
Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Grade >=2 Infusion Related Reactions up to Day 4
Infusion-related reactions are defined as any relevant adverse event that occurs during the infusion or up to day 4. The severity of adverse events (including test findings classified as adverse events) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).
Up to Day 4
Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Grade >=2 Hypersensitivity Reactions Up to Day 29
Hypersensitivity reactions are defined as any relevant adverse event that occurs during the infusion or up to study day 29. The severity of adverse events (including test findings classified as adverse events) were graded according to NCI-CTCAE.
Up to Day 29
Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Cumulative Incidence of Death or Mechanical Ventilation Based on Seronegative mFAS
Cumulative incidence percentage was estimated using Kaplan-Meier method.
Up to Day 29
Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Cumulative Incidence of Death or Mechanical Ventilation Based on High Viral Load mFAS
Cumulative incidence percentage was estimated using Kaplan-Meier method.
Up to Day 29
Secondary Outcomes (54)
Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on High Viral Load mFAS
by Day 29
Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on Seronegative mFAS
by Day 29
Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 Through Day 29 Based on High Viral Load mFAS
Day 6 to Day 29
Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 Through Day 29 Based on Seronegative mFAS
Day 6 to Day 29
Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 Through Day 29 Based on High Viral Load mFAS
Day 1 to Day 29
- +49 more secondary outcomes
Study Arms (4)
On Low-Flow Oxygen
EXPERIMENTALCohort 1 (C1): O2 saturation \>93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device
With COVID-19 symptoms but not requiring supplemental O2
EXPERIMENTALCohort 1A (C1A): With COVID-19 symptoms but not requiring supplemental oxygen
High O2 No Mechanical Ventilation
EXPERIMENTALCohort 2 (C2): On high-intensity oxygen (O2) therapy but not on mechanical ventilation
On Mechanical Ventilation
EXPERIMENTALCohort 3 (C3): On mechanical ventilation
Interventions
Administered intravenously (IV) single dose
Placebo IV Single Dose
Eligibility Criteria
You may qualify if:
- Has SARS-CoV-2-positive antigen or molecular diagnostic test (by validated SARS-CoV-2 antigen, RT-PCR, or other molecular diagnostic assay, using an appropriate sample such as NP, nasal, oropharyngeal \[OP\], or saliva) ≤72 hours prior to randomization and no alternative explanation for current clinical condition. A historical record of positive result from test conducted ≤72 hours prior to randomization is acceptable.
- Has symptoms consistent with COVID-19, as determined by investigator, with onset ≤10 days before randomization
- Hospitalized for ≤72 hours with at least 1 of the following at randomization; patients meeting more than one criterion will be categorized in the most severely affected category:
- Cohort 1A: With COVID-19 symptoms but not requiring supplemental oxygen
- Cohort 1: Maintains O2 saturation \>93% on low-flow oxygen as defined in the protocol
- Cohort 2: High-intensity oxygen therapy without mechanical ventilation as defined in the protocol
- Cohort 3: On mechanical ventilation
You may not qualify if:
- Phase 1 Only: Patients maintaining O2 saturation \>94% on room air
- In the opinion of the investigator, unlikely to survive for \>48 hours from screening
- Receiving extracorporeal membrane oxygenation (ECMO)
- Has new-onset stroke or seizure disorder during hospitalization
- Initiated on renal replacement therapy due to COVID-19
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (123)
Regeneron Study Site
Birmingham, Alabama, 35249, United States
Regeneron Study Site
Chandler, Arizona, 85224, United States
Regeneron Study Site
Phoenix, Arizona, 85006, United States
Regeneron Study Site 1
Tucson, Arizona, 85724, United States
Regeneron Study Site
Long Beach, California, 90806, United States
Regeneron Study Site
Mission Hills, California, 91345, United States
Regeneron Study Site
Sacramento, California, 95817, United States
Regeneron Study Site
Santa Monica, California, 90404, United States
Regeneron Study Site
Stanford, California, 94305, United States
Regeneron Study Site
Aurora, Colorado, 80045, United States
Regeneron Study Site
Boca Raton, Florida, 33486, United States
Regeneron Study Site
Ft. Pierce, Florida, 34982, United States
Regeneron Study Site
Gainesville, Florida, 32610, United States
Regeneron Study Site
Orlando, Florida, 32803, United States
Regeneron Study Site
Pensacola, Florida, 32504, United States
Regeneron Study Site
Sarasota, Florida, 34239, United States
Regeneron Study Site
Tampa, Florida, 33612, United States
Regeneron Study Site
Atlanta, Georgia, 30309, United States
Regeneron Study Site
Atlanta, Georgia, 30322, United States
Regeneron Study Site
Augusta, Georgia, 30912, United States
Regeneron Study Site
Marietta, Georgia, 30060, United States
Regeneron Study Site
Chicago, Illinois, 60611, United States
Regeneron Study Site
Chicago, Illinois, 60612, United States
Regeneron Study Site
Glenview, Illinois, 60026, United States
Regeneron Study Site
Urbana, Illinois, 61801, United States
Regeneron Study Site
Indianapolis, Indiana, 46260, United States
Regeneron Study Site
Iowa City, Iowa, 52242, United States
Regeneron Study Site
Louisville, Kentucky, 40202, United States
Regeneron Study Site
Louisville, Kentucky, 40217, United States
Regeneron Study Site
New Orleans, Louisiana, 70112, United States
Regeneron Study Site
New Orleans, Louisiana, 70122, United States
Regeneron Study Site
Baltimore, Maryland, 21201, United States
Regeneron Study Site
Boston, Massachusetts, 02111, United States
Regeneron Study Site
Boston, Massachusetts, 02115, United States
Regeneron Study Site
Boston, Massachusetts, 02118, United States
Regeneron Study Site
Grand Rapids, Michigan, 49503, United States
Regeneron Study Site
Royal Oak, Michigan, 48073, United States
Regeneron Study Site
Rochester, Minnesota, 55905, United States
Regeneron Study Site
Chesterfield, Missouri, 63017, United States
Regeneron Study Site
St Louis, Missouri, 63104, United States
Regeneron Study Site
St Louis, Missouri, 63110, United States
Regeneron Study Site
Omaha, Nebraska, 68198-5400, United States
Regeneron Study Site
Las Vegas, Nevada, 89109, United States
Regeneron Study Site
Englewood, New Jersey, 07631, United States
Regeneron Study Site
Hackensack, New Jersey, 07601, United States
Regeneron Study Site
Morristown, New Jersey, 07960, United States
Regeneron Study Site
Neptune City, New Jersey, 07753, United States
Regeneron Study Site
Pennington, New Jersey, 08534, United States
Regeneron Study Site
Summit, New Jersey, 07901, United States
Regeneron Study Site
Teaneck, New Jersey, 07666, United States
Regeneron Study Site
Albuquerque, New Mexico, 87108, United States
Regeneron Study Site
Brooklyn, New York, 11219, United States
Regeneron Study Site
Buffalo, New York, 14203, United States
Regeneron Study Site 1
Buffalo, New York, 14215, United States
Regeneron Study Site 2
Buffalo, New York, 14215, United States
Regeneron Study Site
Jamaica, New York, 11432, United States
Regeneron Study Site
New York, New York, 10003, United States
Regeneron Study Site
New York, New York, 10019, United States
Regeneron Study Site
New York, New York, 10025, United States
Regeneron Study Site
New York, New York, 10029, United States
Regeneron Study Site
New York, New York, 10032, United States
Regeneron Study Site
New York, New York, 10037, United States
Regeneron Study Site
Rochester, New York, 14642, United States
Regeneron Study Site
Syracuse, New York, 13210, United States
Regeneron Study Site
The Bronx, New York, 10451, United States
Regeneron Study Site
The Bronx, New York, 10461, United States
Regeneron Study Site
West Islip, New York, 11795, United States
Regeneron Study Site
White Plains, New York, 10601, United States
Regeneron Study Site
Chapel Hill, North Carolina, 27599, United States
Regeneron Study Site
Greensboro, North Carolina, 27408, United States
Regeneron Study Site
Columbus, Ohio, 43210, United States
Regeneron Study Site
Columbus, Ohio, 43215, United States
Regeneron Study Site
Dayton, Ohio, 45409, United States
Regeneron Study Site
Portland, Oregon, 97213, United States
Regeneron Study Site
Portland, Oregon, 97239, United States
Regeneron Study Site
Philadelphia, Pennsylvania, 19140, United States
Regeneron Study Site
Providence, Rhode Island, 02903, United States
Regeneron Study Site
Providence, Rhode Island, 02906, United States
Regeneron Study Site
Sioux Falls, South Dakota, 57108, United States
Regeneron Study Site 1
Amarillo, Texas, 79106, United States
Regeneron Study Site 2
Amarillo, Texas, 79106, United States
Regeneron Study Site
Dallas, Texas, 75235, United States
Regeneron Study Site
Dallas, Texas, 75246, United States
Regeneron Study Site
Dallas, Texas, 75390, United States
Regeneron Study Site
Houston, Texas, 77004, United States
Regeneron Study Site
Houston, Texas, 77024, United States
Regeneron Study Site
Houston, Texas, 77030, United States
Regeneron Study Site
Lubbock, Texas, 79410, United States
Regeneron Study Site
Sugar Land, Texas, 77479, United States
Regeneron Study Site
Tyler, Texas, 75701, United States
Regeneron Study Site
Murray, Utah, 84107, United States
Regeneron Study Site
Salt Lake City, Utah, 84143, United States
Regeneron Study Site
Richmond, Virginia, 23298, United States
Regeneron Study Site
Everett, Washington, 98201, United States
Regeneron Study Site 1
Seattle, Washington, 98122, United States
Regeneron Study Site
Madison, Wisconsin, 53792, United States
Regeneron Study Site
Fortaleza, Ceará, 60160-230, Brazil
Regeneron Study Site
Salvador, Estado de Bahia, 40170-130, Brazil
Regeneron Study Site
Curitiba, Paraná, 80810-040, Brazil
Regeneron Study Site
Passo Fundo, Rio Grande do Sul, 99010-170, Brazil
Regeneron Study Site
Porto Alegre, Rio Grande do Sul, 90610-000, Brazil
Regeneron Study Site
Chapecó, Santa Catarina, 89801-355, Brazil
Regeneron Study Site
Criciúma, Santa Catarina, 88811-508, Brazil
Regeneron Study Site
Botucatu, São Paulo, 18618-686, Brazil
Regeneron Study Site
Campinas, São Paulo, 13060-080, Brazil
Regeneron Study Site
São Paulo, 02401- 400, Brazil
Regeneron Study Site
São Paulo, 04012-909, Brazil
Regeneron Study Site
São Paulo, 05403-010, Brazil
Regeneron Study Site 1
Las Condes, Santiago de Chile, 7591047, Chile
Regeneron Study Site 2
Las Condes, Santiago de Chile, 7591047, Chile
Regeneron Study Site
Vitacura, Santiago de Chile, 7650568, Chile
Regeneron Study Site
Santiago, 7500691, Chile
Regeneron Study Site
Guadalajara, Jalisco, 44340, Mexico
Regeneron Study Site
Monterrey, Nuevo León, 64718, Mexico
Regeneron Study Site
Culiacán, Sinaloa, 80020, Mexico
Regeneron Study Site
Culiacán, 80230, Mexico
Regeneron Study Site 1
Mérida, 97000, Mexico
Regeneron Study Site 2
Mérida, 97000, Mexico
Regeneron Study Site
Monterrey, 64060, Mexico
Regeneron Study Site
Veracruz, 91700, Mexico
Regeneron Study Site
Zapopan, 45170, Mexico
Regeneron Study Site
Chisinau, MD-2025, Moldova
Regeneron Study Site
Bucharest, 021105, Romania
Related Publications (5)
Somersan-Karakaya S, Mylonakis E, Mou J, Oviedo-Orta E, O'Brien MP, Mas Casullo V, Mahmood A, Hooper AT, Hussein M, Ali S, Marty FM, Forleo-Neto E, Bhore R, Hamilton JD, Herman GA, Hirshberg B, Weinreich DM. Effectiveness of Casirivimab and Imdevimab Antibody Combination in Immunocompromised Hospitalized Patients With Coronavirus Disease 2019: A Post Hoc Analysis in a Phase 1/2/3 Double-Blind Trial. Open Forum Infect Dis. 2023 Apr 19;10(5):ofad211. doi: 10.1093/ofid/ofad211. eCollection 2023 May.
PMID: 37229174DERIVEDHooper AT, Somersan-Karakaya S, McCarthy SE, Mylonakis E, Ali S, Mei J, Bhore R, Mahmood A, Geba GP, Dakin P, Weinreich DM, Yancopoulos GD, Herman GA, Hamilton JD; COVID-19 Phase 2/3 Hospitalized Trial Team. Casirivimab and Imdevimab Treatment Reduces Viral Load and Improves Clinical Outcomes in Seropositive Hospitalized COVID-19 Patients with Nonneutralizing or Borderline Neutralizing Antibodies. mBio. 2022 Dec 20;13(6):e0169922. doi: 10.1128/mbio.01699-22. Epub 2022 Oct 18.
PMID: 36255239DERIVEDSomersan-Karakaya S, Mylonakis E, Menon VP, Wells JC, Ali S, Sivapalasingam S, Sun Y, Bhore R, Mei J, Miller J, Cupelli L, Forleo-Neto E, Hooper AT, Hamilton JD, Pan C, Pham V, Zhao Y, Hosain R, Mahmood A, Davis JD, Turner KC, Kim Y, Cook A, Kowal B, Soo Y, DiCioccio AT, Geba GP, Stahl N, Lipsich L, Braunstein N, Herman GA, Yancopoulos GD, Weinreich DM; COVID-19 Phase 2/3 Hospitalized Trial Team. Casirivimab and Imdevimab for the Treatment of Hospitalized Patients With COVID-19. J Infect Dis. 2022 Dec 28;227(1):23-34. doi: 10.1093/infdis/jiac320.
PMID: 35895508DERIVEDHirsch C, Park YS, Piechotta V, Chai KL, Estcourt LJ, Monsef I, Salomon S, Wood EM, So-Osman C, McQuilten Z, Spinner CD, Malin JJ, Stegemann M, Skoetz N, Kreuzberger N. SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19. Cochrane Database Syst Rev. 2022 Jun 17;6(6):CD014945. doi: 10.1002/14651858.CD014945.pub2.
PMID: 35713300DERIVEDKreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
PMID: 34473343DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Trial Management
- Organization
- Regeneron Pharmaceuticals, Inc
Study Officials
- STUDY DIRECTOR
Clinical Trial Management
Regeneron Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 8, 2020
First Posted
June 11, 2020
Study Start
June 10, 2020
Primary Completion
May 7, 2021
Study Completion
October 22, 2021
Last Updated
January 27, 2023
Results First Posted
July 25, 2022
Record last verified: 2023-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, 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).
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing