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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04426695
Recruitment Status : Recruiting
First Posted : June 11, 2020
Last Update Posted : June 26, 2020
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Study Description
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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
  • To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo in improving clinical status Phase 3
  • To evaluate and confirm the clinical efficacy of REGN10933+REGN10987 compared to placebo in improving clinical status

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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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1860 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
Estimated Primary Completion Date : March 3, 2021
Estimated Study Completion Date : March 3, 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

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

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

Drug: Placebo
Placebo IV Single Dose


Outcome Measures
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Primary Outcome Measures :
  1. Proportion of patients with treatment-emergent Serious Adverse Events (SAEs) [ Time Frame: Through Day 169 ]

    Primary:

    Up to Day 169: Phase 1: C1

    Secondary:

    Up to Day 29: Phase 1: C1, Phase 2: C1, C2, C3 Up to Day 57: Phase 2: C1, C2, C3


  2. Proportion of patients with infusion-related reactions [ Time Frame: Through Day 4 ]
    Primary: Phase 1:C1 Secondary: Phase 2: C1, C2, C3

  3. Proportion of patients with hypersensitivity reactions [ Time Frame: Through Day 29 ]
    Primary: Phase 1:C1 Secondary: Phase 2: C1, C2, C3

  4. Time-weighted average change from baseline viral shedding as measured by quantitative reverse transcription 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 viral shedding as measured by RT-qPCR in saliva samples [ Time Frame: Baseline up to Day 22 ]

    Primary:

    Phase 2:C1, C2, C3

    Secondary:

    Phase 1:C1


  6. Proportion of patients with at least 1-point improvement on a 7-Point Ordinal Scale in clinical status [ Time Frame: Day 1, Day 8, Day 22, Day 29 ]

    Primary:

    Day 8: Phase 2:C1, Phase 3:C1 Day 22: Phase 2:C2, C3, Phase 3:C2, C3

    Secondary:

    Day 8: Phase 1:C1 Day 29: Phase 1:C1, Phase 2:C1, C2, C3

    7-point Ordinal Scale:

    • Death;
    • Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO);
    • Hospitalized, requiring non-invasive ventilation or high flow oxygen devices;
    • Hospitalized, requiring supplemental oxygen;
    • Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)
    • Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care
    • Not hospitalized


Secondary Outcome Measures :
  1. Time-weighted average change from baseline viral shedding as measured by RT-qPCR in nasal samples [ Time Frame: Day 1 up to Day 22 ]
    Phase 1: C1 Phase 2: C1, C2, C3

  2. Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR in any tested samples [ Time Frame: Through Day 57 ]
    Phase 1: C1 Phase 2: C1, C2, C3

  3. Change from baseline in SARS-CoV-2 viral shedding as measured by RT-qPCR in NP swabs [ Time Frame: Baseline up to Day 29 ]
    Phase 1: C1

  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 ]
    Phase 1: C1, Phase 2: C1, C2, C3

  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 ]
    Phase 1: C1, Phase 2: C1, C2, C3

  6. Proportion of patients with at least 2-point improvement on a 7-Point Ordinal Scale in clinical status [ Time Frame: Baseline to Day 8, Day 22, Day 29 ]

    Phase 1: C1, Phase 2: C1 Day 8

    Phase 2: C2, C3 Day 22

    Phase 1: C1, Phase 2: C1, C2, C3 Day 29


  7. Time to no longer requiring oxygen supplementation [ Time Frame: Through Day 29 ]
    Phase 1: C1 Phase 2: C1, C2, C3

  8. Number of days of supplemental oxygen use [ Time Frame: Through Day 29 ]
    Phase 1: C1 Phase 2: C1, C2, C3

  9. Proportion of patients initiating high-intensity oxygen therapy [ Time Frame: Up to Day 29 or hospital discharge ]
    Phase 1: C1 Phase 2: C1, C2, C3

  10. Number of days of high-intensity oxygen therapy [ Time Frame: Through Day 29 ]
    Phase 1: C1 Phase 2: C1, C2, C3

  11. Proportion of patients initiating mechanical ventilation [ Time Frame: Up to Day 29 or hospital discharge ]
    Phase 1: C1 Phase 2: C1, C2, C3

  12. Number of days of mechanical ventilation [ Time Frame: Through Day 29 ]
    Phase 1: C1 Phase 2: C1, C2, C3

  13. Number of Ventilator-free days [ Time Frame: Through Day 29 ]
    Phase 1: C1 Phase 2: C1, C2, C3

  14. Number of days of hospitalization [ Time Frame: Through Day 29 ]
    Phase 1: C1 Phase 2: C1, C2, C3

  15. Proportion of patients re-admitted to hospital after discharge through the end of study [ Time Frame: Through Day 169 ]

    Phase 1: C1:

    Through Day 169

    Phase 2: C1, C2, C3:

    Through Day 57


  16. Number of deaths due to any cause (All-Cause Mortality) [ Time Frame: Through Day 169 ]

    Phase 1: C1 Through Day 29 and Day 169

    Phase 2: C1, C2, C3 Through Day 29 and Day 57


  17. Overall Survival [ Time Frame: Through Day 57 ]

    Phase 1: C1:

    Through Day 169

    Phase 2: C1, C2, C3:

    Through Day 57


  18. Serum concentration of REGN10933 over time [ Time Frame: Through Day 57 ]
  19. Serum concentration of REGN10987 over time [ Time Frame: Through Day 57 ]
  20. Incidence of anti-drug antibodies (ADA) to REGN10933 [ Time Frame: Through Day 57 ]
  21. Incidence of anti-drug antibodies (ADA) to REGN10987 [ Time Frame: Through Day 57 ]
  22. Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of REGN10933 [ Time Frame: Through day 169 ]
    Phase 1 only

  23. Assessment of PK parameter: maximum serum concentration observed (Cmax) of REGN10987 [ Time Frame: Through day 169 ]
    Phase 1 only

  24. Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) for REGN10933 [ Time Frame: Through Day 169 ]
    Phase 1 only

  25. Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) for REGN10987 [ Time Frame: Through Day 169 ]
    Phase 1 only

  26. Assessment of PK parameter: Time to Cmax (tmax) for REGN10933 [ Time Frame: Through Day 169 ]
    Phase 1 only

  27. Assessment of PK parameter: Time to Cmax (tmax) for REGN10987 [ Time Frame: Through Day 169 ]
    Phase 1 only

  28. 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 169 ]
    Phase 1 only

  29. Assessment of PK parameter: AUC computed from time zero to the time of the last positive concentration (AUClast) for REGN10987 [ Time Frame: Through Day 169 ]
    Phase 1 only

  30. Assessment of PK parameter: AUC from time zero extrapolated to infinity (AUCinf) for REGN10933 [ Time Frame: Through Day 169 ]
    Phase 1 only

  31. Assessment of PK parameter: AUC from time zero extrapolated to infinity (AUCinf) for REGN10987 [ Time Frame: Through Day 169 ]
    Phase 1 only

  32. Assessment of PK parameter: AUCinf-to-dose ratio (AUCinf/dose) of REGN10933 [ Time Frame: Through Day 169 ]
    Phase 1 only

  33. Assessment of PK parameter: AUCinf-to-dose ratio (AUCinf/dose) of REGN10987 [ Time Frame: Through Day 169 ]
    Phase 1 only

  34. Assessment of PK parameter: Observed terminal half-life [t1/2] for REGN10933 [ Time Frame: Through Day 169 ]
    Phase 1 only

  35. Assessment of PK parameter: Observed terminal half-life [t1/2] of REGN10987 [ Time Frame: Through Day 169 ]
    Phase 1 only

  36. Assessment of PK parameter: Clearance (CL) for REGN10933 [ Time Frame: Through Day 169 ]
    Phase 1 only

  37. Assessment of PK parameter: Clearance (CL) of REGN10987 [ Time Frame: Through Day 169 ]
    Phase 1 only

  38. Assessment of PK parameter: Volume of distribution at steady state (Vss) of REGN10933 [ Time Frame: Through Day 169 ]
    Phase 1 only

  39. Assessment of PK parameter: Volume of distribution at steady state (Vss) of REGN10987 [ Time Frame: Through Day 169 ]
    Phase 1 only

  40. Assessment of PK parameter: Mean residence time (MRT) of REGN10933 [ Time Frame: Through Day 169 ]
    Phase 1 only

  41. Assessment of PK parameter: Mean residence time (MRT) of REGN10987 [ Time Frame: Through Day 169 ]
    Phase 1 only


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

Key Inclusion Criteria:

  • Laboratory-confirmed SARS-CoV-2 infection as defined in the protocol
  • COVID-19 symptom onset ≤7 days

  • Hospitalized for COVID-19 illness 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 1:Maintains O2 saturation >93% on low-flow oxygen as defined in the protocol
    2. Cohort 2: High-intensity oxygen therapy without mechanical ventilation as defined in the protocol
    3. Cohort 3: On mechanical ventilation

Key Exclusion Criteria:

  • 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


Contacts
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Contact: Clinical Trials Administrator 844-734-6643 clinicaltrials@regeneron.com

Locations
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United States, Colorado
Regeneron Study Site Recruiting
Aurora, Colorado, United States, 80045
United States, Georgia
Regeneron Study Site Recruiting
Atlanta, Georgia, United States, 30322
United States, Missouri
Regeneron Study Site Recruiting
Saint Louis, Missouri, United States, 63104
United States, New Jersey
Regeneron Study Site Recruiting
Teaneck, New Jersey, United States, 07666
United States, New York
Regeneron Study Site Recruiting
Bronx, New York, United States, 10451
Regeneron Study Site Recruiting
Bronx, New York, United States, 10461
United States, Pennsylvania
Regeneron Study Site Recruiting
Philadelphia, Pennsylvania, United States, 19140
United States, Texas
Regeneron Study Site Recruiting
Dallas, Texas, United States, 75246
Regeneron Study Site Recruiting
Tyler, Texas, United States, 75708
Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
More Information
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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04426695    
Other Study ID Numbers: R10933-10987-COV-2066
First Posted: June 11, 2020    Key Record Dates
Last Update Posted: June 26, 2020
Last Verified: June 2020
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