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Trial record 1 of 1 for:    NCT04425629
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Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Adult and Pediatric 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: NCT04425629
Recruitment Status : Terminated (Emerging SARS-CoV-2 variants impacting susceptibility to study drug)
First Posted : June 11, 2020
Last Update Posted : July 29, 2022
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Study Description
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Brief Summary:

Phase 1

  • 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 load of SARS-CoV-2

Phase 2

• To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral load of SARS-CoV-2

Phase 3

  • Cohort 1 (≥18 Years Old, Not Pregnant at Randomization)

    • To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo as measured by COVID-19-related hospitalizations or all-cause death

  • Cohort 2 (<18 Years Old, Not Pregnant at Randomization)

    • To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo
    • To further characterize the concentrations of REGN10933 and REGN10987 in serum over time
  • Cohort 3 (Pregnant at Randomization) • To evaluate the safety and tolerability of REGN10933+REGN10987

Condition or disease Intervention/treatment Phase
COVID-19 Drug: casirivimab+imdevimab combination therapy Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10078 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Phase 1/Phase 2/Phase 3
Masking: None (Open Label)
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 Ambulatory Patients With COVID-19
Actual Study Start Date : June 16, 2020
Actual Primary Completion Date : January 21, 2022
Actual Study Completion Date : June 9, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: casirivimab+imdevimab low dose
Low dose or body-weight equivalent for those under 18 years of age.
 Drug: casirivimab+imdevimab combination therapy
Administered intravenously (IV) single dose
Other Names:
  • REGN-COV2
  • REGN10933
  • REGN10987
  • REGEN-COV™
  • Ronapreve™


Outcome Measures
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Primary Outcome Measures :
  1. Proportion of patients with treatment-emergent serious adverse events (SAEs) [ Time Frame: Through Day 29 ]

    Primary:

    Phase 1, Phase 3 (Cohort 2 and Cohort 3)

    Secondary:

    Phase 2, Phase 3 (Cohort 1)


  2. Proportion of patients with infusion-related reactions [ Time Frame: Through Day 4 ]

    Primary:

    Phase 1, Phase 3 (Cohort 2 and Cohort 3)

    Secondary:

    Phase 2, Phase 3 (Cohort 1)


  3. Proportion of patients with hypersensitivity reactions [ Time Frame: Through Day 29 ]

    Primary:

    Phase 1, Phase 3 (Cohort 2 and Cohort 3)

    Secondary:

    Phase 2, Phase 3 (Cohort 1)


  4. Time-weighted average change from baseline in viral load (log10 copies/mL), as measured by quantitative reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples [ Time Frame: Baseline up to Day 7 ]

    Primary:

    Phase 1, Phase 2

    Secondary:

    Phase 3 (Cohort 1, for patients enrolled prior to protocol amendment 6 only), Phase 3 (Cohort 2)


  5. Proportion of patients with at least one (≥1) COVID-19-related hospitalization or all-cause death [ Time Frame: Through Day 29 ]

    Primary:

    Phase 3 (Cohort 1)

    Secondary:

    Phase 3 (Cohort 2)


  6. Concentration of REGN10933 in serum over time [ Time Frame: Through Day 29 ]

    Primary:

    Phase 3 (Cohort 2)

    Secondary:

    Phase 1, Phase 2, Phase 3 (Cohort 1, Cohort 2 and Cohort 3)


  7. Concentration of REGN10987 in serum over time [ Time Frame: Through Day 29 ]

    Primary:

    Phase 3 (Cohort 2)

    Secondary:

    Phase 1, Phase 2, Phase 3 (Cohort 1, Cohort 2 and Cohort 3)



Secondary Outcome Measures :
  1. Time-weighted average change from baseline in viral load (log10 copies/mL), as measured by RT-qPCR in saliva samples [ Time Frame: Baseline up to Day 22 ]
    Phase 1 Only

  2. Time-weighted average change from baseline in viral load (log10 copies/mL), as measured by RT-qPCR in nasal swab samples [ Time Frame: Baseline up to Day 22 ]
    Phase 1 Only

  3. Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR in any tested samples [ Time Frame: Through Day 29 ]
    Phase 1 Only

  4. Time to negative RT-qPCR in nasopharyngeal swabs with no subsequent positive RT-qPCR [ Time Frame: Through Day 29 ]
    Phase 2 Only

  5. Change from baseline in viral load at each visit, as measured by RT-qPCR in nasopharyngeal swabs [ Time Frame: Baseline up to Day 29 ]
    Phase 1, Phase 2, Phase 3 (Cohort 1 and Cohort 2)

  6. Change from baseline in viral load at each visit, as measured by RT-qPCR in saliva samples [ Time Frame: Baseline up to Day 29 ]
    Phase 1 Only

  7. Change from baseline in viral load at each visit, as measured by RT-qPCR in nasal swabs [ Time Frame: Baseline up to Day 29 ]
    Phase 1 Only

  8. Correlation of RT-qPCR results over time between different sample types (NP, nasal, and saliva) [ Time Frame: Up to Day 29 ]
    Phase 1 Only

  9. Concordance of RT-qPCR results over time between different sample types (NP, nasal, and saliva) [ Time Frame: Up to Day 29 ]
    Phase 1 Only

  10. Time-weighted average change from baseline in viral load (log10 copies/mL) from day 1 to post-baseline study days [ Time Frame: Day 1 to Day 29 ]
    Phase 1, Phase 2

  11. Proportion of participants with ≥1 COVID-19-related medically-attended visit [ Time Frame: Through Day 29 ]
    Phase 1, Phase 2

  12. Proportion of participants with ≥2 COVID-19-related medically-attended visit [ Time Frame: Through Day 29 ]
    Phase 1, Phase 2, Phase 3 (Cohort 1 and Cohort 2)

  13. Total number of COVID-19-related medically-attended visits [ Time Frame: Through Day 29 ]
    Phase 1, Phase 2, Phase 3 (Cohort 1 and Cohort 2)

  14. Proportion of participants admitted to a hospital due to COVID-19 [ Time Frame: Through Day 29 ]
    Phase 1, Phase 2

  15. Proportion of participants with ≥1 outpatient or telemedicine visit due to COVID-19 [ Time Frame: Through Day 29 ]
    Phase 1, Phase 2

  16. Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of REGN10933 [ Time Frame: Through Day 29 ]
    Phase 1 Only

  17. Assessment of PK parameter: maximum serum concentration observed (Cmax) of REGN10987 [ Time Frame: Through Day 29 ]
    Phase 1 Only

  18. Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10933 [ Time Frame: Through Day 29 ]
    Phase 1 Only

  19. Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10987 [ Time Frame: Through Day 29 ]
    Phase 1 Only

  20. Assessment of PK parameter: Time to Cmax (tmax) for REGN10933 [ Time Frame: Through Day 29 ]
    Phase 1 Only

  21. Assessment of PK parameter: Time to Cmax (tmax) for REGN10987 [ Time Frame: Through Day 29 ]
    Phase 1 Only

  22. 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

  23. 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

  24. Immunogenicity as measured by anti-drug (ADA) to REGN10933 [ Time Frame: Through Day 29 ]
    Phase 1, Phase 2, Phase 3 (Cohort 1, Cohort 2 and Cohort 3)

  25. Immunogenicity as measured by ADA to REGN10987 [ Time Frame: Through Day 29 ]
    Phase 1, Phase 2, Phase 3 (Cohort 1, Cohort 2 and Cohort 3)

  26. Immunogenicity as measured by neutralizing antibodies (NAbs) to REGN10933 [ Time Frame: Through Day 29 ]
    Phase 2, Phase 3 (Cohort 1, Cohort 2 and Cohort 3)

  27. Immunogenicity as measured by NAbs to REGN10987 [ Time Frame: Through Day 29 ]
    Phase 2, Phase 3 (Cohort 1, Cohort 2 and Cohort 3)

  28. Proportion of participants with high viral load at each visit [ Time Frame: Through Day 29 ]
    Phase 2 Only

  29. Proportion of participants with viral loads below the limit of detection at each visit [ Time Frame: Through Day 29 ]
    Phase 2 Only

  30. Proportion of participants with viral loads below the lower limit of quantitation at each visit [ Time Frame: Through Day 29 ]
    Phase 2 Only

  31. Proportion of participants admitted to an intensive care unit (ICU) due to COVID-19 [ Time Frame: Through Day 29 ]
    Phase 2, Phase 3 (Cohort 1 and Cohort 2)

  32. Proportion of participants requiring mechanical ventilation due to COVID-19 [ Time Frame: Through Day 29 ]
    Phase 2, Phase 3 (Cohort 1 and Cohort 2)

  33. Number of days of hospitalization due to COVID-19 [ Time Frame: Through Day 29 ]
    Phase 2, Phase 3 (Cohort 1 and Cohort 2)

  34. Proportion of participants with all-cause mortality [ Time Frame: Through Day 29 ]
    Phase 2 Only

  35. Time to first onset of symptoms consistent with COVID-19 (asymptomatic cohort only) [ Time Frame: Up to Day 29 ]
    Phase 2 Only

  36. Duration of symptoms consistent with COVID-19 [ Time Frame: Up to Day 29 ]
    Phase 2 Only

  37. Proportion of participants with ≥1 COVID-19-related hospitalization or all-cause death [ Time Frame: From Day 4 Through Day 29 ]
    Phase 3 (Cohort 1 and Cohort 2)

  38. Time to COVID-19 symptoms resolution [ Time Frame: Through Day 29 ]
    Phase 3 (Cohort 1)

  39. Proportion of participants with ≥1 COVID-19-related hospitalization, emergency room visit, or all-cause death [ Time Frame: Through day 29 ]
    Phase 3 (Cohort 1 and Cohort 2)

  40. Proportion of patients with (≥1) COVID-19-related medically-attended visit or all-cause death [ Time Frame: Through Day 29 ]
    Phase 3 (Cohort 1 and Cohort 2)

  41. Proportion of participants with ≥1 COVID-19-related medically-attended visit by type of visit [ Time Frame: Through day 29 ]

    Phase 3 (Cohort 1 and Cohort 2)

    Type of visit defined as hospitalization, emergency room, urgent care, and/or physician's office/telemedicine


  42. Cumulative incidence of patients with ≥1 COVID-19-related hospitalization or all-cause death [ Time Frame: Through Day 29 ]
    Phase 3 (Cohort 1 and Cohort 2)

  43. Cumulative incidence of patients with ≥1 COVID-19-related hospitalization, emergency room visit, or all-cause death [ Time Frame: Through Day 29 ]
    Phase 3 (Cohort 1 and Cohort 2)

  44. Cumulative incidence of patients with ≥1 COVID-19-related medically-attended visit or all-cause death [ Time Frame: Through Day 29 ]
    Phase 3 (Cohort 1 and Cohort 2)

  45. Proportion of participants requiring supplemental oxygen due to COVID-19 [ Time Frame: Through Day 29 ]
    Phase 3 (Cohort 1 and Cohort 2)

  46. Time to all-cause death [ Time Frame: Through Day 169 ]
    Phase 3 (Cohort 1 and Cohort 2)

  47. All-cause death [ Time Frame: By Day 29, Day 120, and Day 169 ]
    Phase 3 (Cohort 1 and Cohort 2)


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.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Has SARS-CoV-2-positive diagnostic test (from a sample collected ≤72 hours prior to randomization, using a validated SARS-CoV-2 antigen, RT-PCR, or other molecular diagnostic assay, and an appropriate sample such as nasopharyngeal [NP], nasal, oropharyngeal [OP], or saliva)
  • Has symptoms consistent with COVID-19, as determined by the investigator, with onset ≤7 days before randomization
  • Maintains O2 saturation ≥93% on room air
  • Is able to understand and complete study-related questionnaires (patients aged ≥12 years only)

Key Exclusion Criteria:

  • Was admitted to a hospital for COVID-19 prior to randomization, or is hospitalized (inpatient) for any reason at randomization
  • Has participated, or is participating, in a clinical research study evaluating COVID-19 convalescent plasma, mAbs against SARS-CoV-2 (eg, bamlanivimab), or intravenous immunoglobulin (IVIG) within 3 months or within 5 half-lives of the investigational product (whichever is longer) prior to the screening visit
  • Prior, current, or planned future use of any of the following treatments: COVID-19 convalescent plasma, mAbs against SARS-CoV-2 (eg, bamlanivimab), IVIG (any indication), systemic corticosteroids (any indication), or COVID-19 treatments (authorized, approved, or investigational)
  • Prior use (prior to randomization), current use (at randomization) or planned use (within 90 days of study drug administration or per current CDC recommendations, as applicable) of any authorized or approved vaccine for COVID-19
  • Has participated, is participating or plans to participate in a clinical research study evaluation any authorized, approved or investigational vaccine for 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): NCT04425629


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:
Informed Consent Form  [PDF] August 12, 2020

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04425629    
Other Study ID Numbers: R10933-10987-COV-2067
2020-003690-21 ( EudraCT Number )
First Posted: June 11, 2020    Key Record Dates
Last Update Posted: July 29, 2022
Last Verified: July 2022
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
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