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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04426695
Recruitment Status : Completed
First Posted : June 11, 2020
Results First Posted : July 25, 2022
Last Update Posted : January 27, 2023
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Study Description
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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

Condition or disease Intervention/treatment Phase
COVID-19 Drug: REGN10933+REGN10987 combination therapy Drug: Placebo Phase 1 Phase 2

Study Design
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Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2252 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Phase 1/Phase 2/Phase 3
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 10, 2020
Actual Primary Completion Date : May 7, 2021
Actual Study Completion Date : October 22, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: On Low-Flow Oxygen
Cohort 1 (C1): O2 saturation >93% on low-flow oxygen via nasal cannula, simple face mask, or other similar device
 Drug: REGN10933+REGN10987 combination therapy
Administered intravenously (IV) single dose
Other Names:
  • REGN-COV2
  • REGEN-COV™
  • Ronapreve™
  • casirivimab
  • imdevimab

Drug: Placebo
Placebo IV Single Dose
Experimental: With COVID-19 symptoms but not requiring supplemental O2
Cohort 1A (C1A): With COVID-19 symptoms but not requiring supplemental oxygen
 Drug: REGN10933+REGN10987 combination therapy
Administered intravenously (IV) single dose
Other Names:
  • REGN-COV2
  • REGEN-COV™
  • Ronapreve™
  • casirivimab
  • imdevimab

Drug: Placebo
Placebo IV Single Dose
Experimental: High O2 No Mechanical Ventilation
Cohort 2 (C2): On high-intensity oxygen (O2) therapy but not on mechanical ventilation
 Drug: REGN10933+REGN10987 combination therapy
Administered intravenously (IV) single dose
Other Names:
  • REGN-COV2
  • REGEN-COV™
  • Ronapreve™
  • casirivimab
  • imdevimab

Drug: Placebo
Placebo IV Single Dose
Experimental: On Mechanical Ventilation
Cohort 3 (C3): On mechanical ventilation
 Drug: REGN10933+REGN10987 combination therapy
Administered intravenously (IV) single dose
Other Names:
  • REGN-COV2
  • REGEN-COV™
  • Ronapreve™
  • casirivimab
  • imdevimab

Drug: Placebo
Placebo IV Single Dose


Outcome Measures
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Primary Outcome Measures :
  1. 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 Frame: Day 1 to Day 7 ]
    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.

  2. 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 [ Time Frame: Day 6 to Day 29 ]
    Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on high viral load mFAS were reported.

  3. 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 [ Time Frame: Day 6 to Day 29 ]
    Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on seronegative mFAS were reported.

  4. 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 [ Time Frame: Day 6 to Day 29 ]
    Percentage of participants who died or went on mechanical ventilation from Day 6 through Day 29 based on overall FAS were reported.

  5. 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 [ Time Frame: Day 1 to Day 29 ]
    Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on high viral load mFAS were reported.

  6. 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 [ Time Frame: Day 1 to Day 29 ]
    Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on seronegative mFAS were reported.

  7. 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 [ Time Frame: Day 1 to Day 29 ]
    Percentage of participants who died or went on mechanical ventilation from Day 1 through Day 29 based on overall mFAS were reported.

  8. Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Treatment-Emergent Serious Adverse Events [ Time Frame: Up to Day 169 ]
    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.

  9. Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Grade >=2 Infusion Related Reactions up to Day 4 [ Time Frame: 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).

  10. Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Number of Participants With Grade >=2 Hypersensitivity Reactions Up to Day 29 [ Time Frame: 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.

  11. Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Cumulative Incidence of Death or Mechanical Ventilation Based on Seronegative mFAS [ Time Frame: Up to Day 29 ]
    Cumulative incidence percentage was estimated using Kaplan-Meier method.

  12. Pooled Analysis (Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Cumulative Incidence of Death or Mechanical Ventilation Based on High Viral Load mFAS [ Time Frame: Up to Day 29 ]
    Cumulative incidence percentage was estimated using Kaplan-Meier method.


Secondary Outcome Measures :
  1. 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 [ Time Frame: by Day 29 ]
    Percentage of participants who went on mechanical ventilation by Day 29 based on High Viral Load mFAS in pooled analysis phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.

  2. 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 [ Time Frame: by Day 29 ]
    Percentage of participants who went on mechanical ventilation at Day 29 based on Seronegative mFAS in pooled analysis phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.

  3. 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 [ Time Frame: Day 6 to Day 29 ]
    Percentage of participants who died from Day 6 through Day 29 based on high viral load mFAS were reported.

  4. 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 [ Time Frame: Day 6 to Day 29 ]
    Percentage of participants who died from Day 6 through Day 29 Based on seronegative mFAS in pooled analysis phase 3 (cohort 1) and phase 2 (cohort 1A) were reported.

  5. 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 [ Time Frame: Day 1 to Day 29 ]
    Percentage of participants who died from Day 1 through Day 29 based on High Viral Load mFAS in pooled analysis phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported.

  6. Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 Through Day 29 Based on Seronegative mFAS [ Time Frame: Day 1 to Day 29 ]
    Percentage of participants who died from Day 1 through Day 29 based on seronegative mFAS in pooled analysis phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported.

  7. Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on High Viral Load mFAS [ Time Frame: by Day 29 ]
    Percentage of participants who were discharged by Day 29 based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported.

  8. Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on Seronegative mFAS [ Time Frame: by Day 29 ]
    Percentage of participants who were discharged by Day 29 based on seronegative mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported.

  9. Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital Over Time Based on High Viral Load mFAS [ Time Frame: Up to Day 29 ]
    Percentage of participants who died or were readmitted to hospital over time based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A)were reported. Readmission to hospital was based on investigator report.

  10. Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital by Day 29 Based on Seronegative mFAS [ Time Frame: by Day 29 ]
    Percentage of participants who died or were readmitted to hospital at Day 29 based on seronegative mFAS in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Readmission to hospital was based on investigator report.

  11. Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death (ie, Overall Survival) by Day 29 Based on High Viral Load mFAS [ Time Frame: by Day 29 ]
    Overall Survival was defined as time interval from randomization to death. Percentage of participants with cumulative incidence of death (ie, overall survival) at Day 29 from randomization based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

  12. Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death (ie, Overall Survival) by Day 29 Based on Seronegative mFAS [ Time Frame: by Day 29 ]
    Overall Survival was defined as time interval from randomization to death. Percentage of participants with cumulative incidence of death (ie, overall survival) at Day 29 from randomization based on seronegative mFAS in phase 3 (Cohort 1) and phase 2 (Cohort 1A)were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

  13. Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation by Day 29 Based on High Viral Load mFAS [ Time Frame: by Day 29 ]
    Number of participants with cumulative incidence of mechanical ventilation by Day 29 based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

  14. Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation by Day 29 Based on Seronegative mFAS [ Time Frame: by Day 29 ]
    Percentage of participants with cumulative incidence of mechanical ventilation by Day 29 based on seronegative mFAS in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

  15. Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation by Day 29 Based on High Viral Load mFAS [ Time Frame: by Day 29 ]
    Percentage of participants with cumulative incidence of death or mechanical ventilation by Day 29 based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

  16. Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation by Day 29 Based on Seronegative mFAS [ Time Frame: by Day 29 ]
    Percentage of participants with cumulative incidence of death or mechanical ventilation by Day 29 based on seronegative mFAS in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

  17. Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge From Hospital Based on High Viral Load mFAS [ Time Frame: Up to Day 56 ]
    Time to discharge from hospital based on High Viral Load mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) was reported.

  18. Pooled Analysis Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge From Hospital Based on Seronegative mFAS [ Time Frame: Up to Day 56 ]
    Time to discharge from hospital based on Seronegative mFAS in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) was reported.

  19. Pooled Analysis (Phases 1/2/3 [Cohort 1] and Phase 2 [Cohorts 1A/2/3]): Number of Participants With Treatment-Emergent Serious Adverse Events [ Time Frame: Up to Day 169 ]
  20. Pooled Analysis (Phases 1/2/3 [Cohort 1] and Phase 2 [Cohorts 1A/2/3]): Number of Participants With Grade >=2 Infusion Related Reactions up to Day 4 [ Time Frame: Up to Day 4 ]
  21. Pooled Analysis (Phases 1/2/3 [Cohort 1] and Phase 2 [Cohorts 1A/2/3]): Number of Participants With Grade >=2 Hypersensitivity Reactions Up to Day 29 [ Time Frame: Up to Day 29 ]
  22. Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Went on Mechanical Ventilation by Day 29 Based on Seronegative mFAS [ Time Frame: by Day 29 ]
    Percentage of participants who went on mechanical ventilation in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.

  23. Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 Through Day 29 Based on Seronegative mFAS [ Time Frame: Day 6 to Day 29 ]
    Percentage of participants who died from Day 6 through Day 29 in phase 3 (cohort 1) and phase 2 (cohort 1A) were reported.

  24. Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 Through Day 29 Based on Seronegative mFAS [ Time Frame: Day 1 to Day 29 ]
    Percentage of participants who died from Day 1 through Day 29 in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported.

  25. Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on Seronegative mFAS [ Time Frame: by Day 29 ]
    Percentage of participants who were discharged in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) by Day 29 were reported.

  26. Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital by Day 29 Based on Seronegative mFAS [ Time Frame: Up to Day 29 ]
    Percentage of participants who died or were readmitted to hospital in phase 3 (Cohort 1) and phase 2 (Cohort 1A) by Day 29 were reported. Readmission to hospital was based on investigator report.

  27. Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death up to Day 29 Based on Seronegative mFAS [ Time Frame: Up to Day 29 ]
    Percentage of participants with cumulative incidence of death in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) up to Day 29 from randomization were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

  28. Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation by Day 29 Based on Seronegative mFAS [ Time Frame: by Day 29 ]
    Percentage of participants with cumulative incidence of mechanical ventilation in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) by Day 29 were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

  29. Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation by Day 29 Based on Seronegative mFAS [ Time Frame: by Day 29 ]
    Percentage of participants with cumulative incidence of death or mechanical ventilation in Phase 3 (Cohort 1) and Phase 2 (Cohort 1A) by Day 29 were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

  30. Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge From Hospital Based on Seronegative mFAS [ Time Frame: Up to Day 56 ]
    Time to discharge from hospital up to Day 56 was reported.

  31. Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: TWA Change From Baseline Viral Load (Seronegative mFAS) in NP Samples up to Day 11 Based on Seronegative mFAS [ Time Frame: Day 1 to Day 11 ]
    TWA change from baseline in viral load up to Day 11 was calculated for each participant using the trapezoidal rule as the area under the curve for change from baseline at each time point divided by the time interval for the observation period. TWA change from baseline viral load in NP samples through Day 11, was measured by RT-qPCR in NP swab samples was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicate improvement in viral load.

  32. Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: TWA Change From Baseline Viral Load (Seronegative mFAS) in NP Samples up to Day 29 [ Time Frame: Day 1 to Day 29 ]
    TWA change from baseline in viral load up to Day 29 was calculated for each participant using the trapezoidal rule as the area under the curve for change from baseline at each time point divided by the time interval for the observation period. TWA change from baseline viral load in NP samples through Day 29, was measured by quantitative RT-qPCR in NP swab samples was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicate improvement in viral load.

  33. Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: Change From Baseline in Viral Load (Seronegative mFAS) as Measured by RT-qPCR in NP Swabs Over Time [ Time Frame: Days 3, 5, 7, 9, 11, 13, 15, 22 and 29 ]
    Change from baseline in viral load as measured by RT-qPCR in NP swabs over time was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicates improvement in viral load.

  34. Phase 3 [Cohort 1] and Phase 2 [Cohort 1A]: Percent Change From Baseline in Viral Load (Seronegative mFAS) as Measured by RT-qPCR in NP Swabs Over Time [ Time Frame: Days 3, 5, 7, 9, 11, 13, 15, 22 and 29 ]
    Percent change from baseline in viral load as measured by RT-qPCR in NP swabs over time was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicates improvement in viral load.

  35. 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 [ Time Frame: by Day 29 ]
    Percentage of participants who went on mechanical ventilation in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.

  36. Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 6 to Day 29 Based on High Viral Load mFAS [ Time Frame: Day 6 to Day 29 ]
    Percentage of participants who died in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.

  37. Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died From Day 1 to Day 29 Based on High Viral Load mFAS [ Time Frame: Day 1 to Day 29 ]
    Percentage of participants who died in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.

  38. Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Were Discharged by Day 29 Based on High Viral Load mFAS [ Time Frame: by Day 29 ]
    Percentage of participants who were discharged in phase 3 (Cohort 1) and phase 2 (Cohort 1A) was reported.

  39. Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Percentage of Participants Who Died or Were Readmitted to Hospital Over Time Based on High Viral Load mFAS [ Time Frame: Up to Day 29 ]
    Percentage of participants who died or were readmitted to hospital in phase 3 (Cohort 1) and phase 2 (Cohort 1A) over time were reported. Readmission to hospital was based on investigator report.

  40. Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death Over Time Based on High Viral Load mFAS [ Time Frame: Up to Day 29 ]
    Cumulative Incidence of Death Over Time in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

  41. Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Mechanical Ventilation Over Time Based on High Viral Load mFAS [ Time Frame: Up to Day 29 ]
    Cumulative Incidence of Mechanical Ventilation Over Time in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

  42. Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Cumulative Incidence of Death or Mechanical Ventilation Over Time Based on High Viral Load mFAS [ Time Frame: Up to Day 29 ]
    Cumulative Incidence of Death or Mechanical Ventilation Over Time in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported. Cumulative incidence percentage was estimated using Kaplan-Meier method.

  43. Phase 3 (Cohort 1) and Phase 2 (Cohort 1A): Time to Discharge Based on High Viral Load mFAS [ Time Frame: Up to Day 56 ]
    Time to Discharge in phase 3 (Cohort 1) and phase 2 (Cohort 1A) were reported.

  44. Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Time-weighted Average (TWA) Change in Viral Load in Nasopharyngeal (NP) Samples Over Time Based on Seronegative mFAS [ Time Frame: Up to Day 29 ]
    Time-weighted average daily change over time up to Day 29 in viral load (log10 copies/mL), as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples.

  45. Phase 1 [Cohort 1] and Phase 2 [Cohort 1]): Change From Baseline as Measured by RT-qPCR in NP Swabs Over Time Based on Seronegative mFAS [ Time Frame: Days 3, 5, 7, 9, 11, 13, 15, 22 and 29 ]
    Change from baseline in viral load as measured by RT-qPCR in NP swabs over time was reported. Baseline was defined as the last non-missing value measured prior to dosing. Negative changes indicates improvement in viral load.

  46. Phase 1 [Cohort 1] and Phase 2 [Cohort 1]: Percentage of Participants Who Died or Went On Mechanical Ventilation by Day 29 Based on Seronegative mFAS [ Time Frame: Through Day 29 ]
  47. Phase 1 [Cohort 1] and Phase 2 [Cohort 1]: Percentage of Participants Who Died or Went On Mechanical Ventilation by Day 29 Based on High Viral Load mFAS [ Time Frame: Through Day 29 ]
  48. Phase 1 [Cohort 1]: Area Under the Concentration-Time Curve From Time 0 to 28 Days Post-dose (AUC0-28) [ Time Frame: Up to Day 28 ]
  49. Concentration at the End of Infusion (Ceoi) [ Time Frame: Day 1 ]
  50. Concentration at Day 28 (C28) [ Time Frame: Day 28 ]
  51. Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10933 [ Time Frame: Through Day 169 ]
  52. Immunogenicity as Measured by Anti-drug Antibodies (ADAs) to REGN10987 [ Time Frame: Through Day 169 ]
  53. Immunogenicity as Measured by Neutralizing Antibody Status (NAb) to REGN10933 [ Time Frame: Through Day 57 ]
  54. Immunogenicity as Measured by Neutralizing Antibody Status (NAb) to REGN10987 [ Time Frame: Through Day 57 ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • 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:

    1. Cohort 1A: With COVID-19 symptoms but not requiring supplemental oxygen
    2. Cohort 1: Maintains O2 saturation >93% on low-flow oxygen as defined in the protocol
    3. Cohort 2: High-intensity oxygen therapy without mechanical ventilation as defined in the protocol
    4. Cohort 3: On mechanical ventilation

Key Exclusion Criteria:

  • 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

NOTE: Other protocol defined inclusion / exclusion criteria apply

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04426695


Locations
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Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Regeneron Pharmaceuticals:
Study Protocol  [PDF] August 27, 2021
Statistical Analysis Plan  [PDF] July 7, 2021

More Information
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04426695    
Other Study ID Numbers: R10933-10987-COV-2066
2020-002537-15 ( EudraCT Number )
First Posted: June 11, 2020    Key Record Dates
Results First Posted: July 25, 2022
Last Update Posted: January 27, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Supporting Materials: 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/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Regeneron Pharmaceuticals:
Coronavirus disease 2019 (COVID-19)
Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2)
coronavirus
acute respiratory distress syndrome
Additional relevant MeSH terms:
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COVID-19
Pneumonia, Viral
Pneumonia
Respiratory Tract Infections
Infections
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
 Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Casirivimab and imdevimab drug combination
Antiviral Agents
Anti-Infective Agents