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Evaluation of the Efficacy and Safety of Sarilumab in Hospitalized 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: NCT04315298
Recruitment Status : Recruiting
First Posted : March 19, 2020
Last Update Posted : April 6, 2020
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Brief Summary:

Phase 2:

The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with COVID-19 regardless of severity strata.

Phase 3:

The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with COVID-19 (severe and critical).


Condition or disease Intervention/treatment Phase
COVID-19 Drug: Sarilumab Drug: Placebo Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Adaptive Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID-19
Actual Study Start Date : March 18, 2020
Estimated Primary Completion Date : March 9, 2021
Estimated Study Completion Date : April 1, 2021


Arm Intervention/treatment
Experimental: Sarilumab high dose Drug: Sarilumab
Single intravenous (IV) dose of sarilumab
Other Names:
  • Kevzara®
  • REGN88
  • SAR153191

Experimental: Sarilumab low dose Drug: Sarilumab
Single intravenous (IV) dose of sarilumab
Other Names:
  • Kevzara®
  • REGN88
  • SAR153191

Placebo Comparator: Placebo Drug: Placebo
Single intravenous (IV) dose of placebo to match sarilumab administration




Primary Outcome Measures :
  1. Percent change in C-reactive protein (CRP) levels [ Time Frame: Day 4 ]
    Phase 2 Only

  2. Time to improvement (2 points) in clinical status assessment using the 7-point ordinal scale in patients with serum IL-6 levels greater than the upper limit of normal [ Time Frame: Up to day 29 ]

    Phase 3 Only

    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 to improvement (2 points) in clinical status assessment on the 7-point ordinal scale in severe or critical patients with serum IL-6 levels greater than the upper limit of normal [ Time Frame: Up to day 29 ]
    Phase 2 Only

  2. Time to improvement (2 points) in clinical status assessment on the 7-point ordinal scale reporting in severe or critical patients with all IL-6 levels [ Time Frame: Up to day 29 ]
    Phase 2 Only

  3. Time to resolution of fever for at least 48 hours without antipyretics in patients with documented fever [ Time Frame: Up to day 29 ]

    Resolution of fever defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary)

    Documented fever defined as ≥38°C (oral), ≥38.4°C (rectal or tympanic), or ≥37.6°C (temporal or axillary)


  4. Time to resolution of fever for at least 48 hours without antipyretics by clinical severity [ Time Frame: Up to day 29 ]
    Defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary)

  5. Time to resolution of fever for at least 48 hours without antipyretics by baseline IL-6 levels [ Time Frame: Up to day 29 ]
    Defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary)

  6. Time to improvement in oxygenation for at least 48 hours [ Time Frame: Up to day 29 ]
    Improvement in oxygenation defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2

  7. Time to improvement in oxygenation for at least 48 hours by clinical severity [ Time Frame: Up to day 29 ]
    Defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2

  8. Time to improvement in oxygenation for at least 48 hours by baseline IL-6 levels [ Time Frame: Up to day 29 ]
    Defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2

  9. Time to resolution of fever and improvement in oxygenation for at least 48 hours [ Time Frame: Up to day 29 ]

    Resolution of fever defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary)

    Improvement in oxygenation defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2


  10. Mean change in the 7-point ordinal scale [ Time Frame: Up to day 29 ]
  11. Percentage of patients in each clinical status category using the 7-point ordinal scale [ Time Frame: Up to day 29 ]
  12. Time to discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and maintained for 24 hours [ Time Frame: Up to day 29 ]
    NEWS2 consists of: Physiological Parameters: Respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), Use of Air or oxygen, Systolic blood pressure (mmHg), Pulse (per minute), Consciousness, Temperature (°C)

  13. Change from baseline in NEWS2 scoring system [ Time Frame: Up to day 29 ]
  14. Number of days with fever [ Time Frame: Up to day 29 ]
    Defined as ≥38°C (oral), ≥38.4°C (rectal or tympanic) or ≥37.6°C (temporal or axillary)

  15. Proportion of patients alive, off oxygen [ Time Frame: Day 29 ]
  16. Number of days of resting respiratory rate >24 breaths/min [ Time Frame: Up to day 29 ]
  17. Number of days with hypoxemia [ Time Frame: Up to day 29 ]
  18. Number of days of supplemental oxygen use [ Time Frame: Up to day 29 ]
  19. Time to saturation ≥94% on room air [ Time Frame: Up to day 29 ]
  20. Number of ventilator free days in the first 28 days [ Time Frame: Baseline to day 29 ]
  21. Number of patients requiring initiation of mechanical ventilation [ Time Frame: Up to day 29 ]
  22. Number of patients requiring non-invasive ventilation [ Time Frame: Up to day 29 ]
  23. Number of patients requiring the use of high flow nasal cannula [ Time Frame: Up to day 29 ]
  24. Number of patients admitted into an intensive care unit (ICU) [ Time Frame: Up to day 29 ]
  25. Number of days of hospitalization among survivors [ Time Frame: Up to day 29 ]
  26. Number of deaths due to any cause [ Time Frame: Up to day 60 ]
  27. Change in serum CRP levels [ Time Frame: Up to day 29 ]
    Phase 3 Only

  28. Incidence of serious adverse events [ Time Frame: Up to Day 29 ]
  29. Incidence of Grade 4 neutropenia (ANC <500/mm3) [ Time Frame: Up to day 29 ]
  30. Incidence of severe or life-threatening bacterial, invasive fungal, or opportunistic infection [ Time Frame: Up to day 29 ]
  31. Incidence of severe or life-threatening bacterial, invasive fungal, or opportunistic infection in patients with Grade 4 neutropenia [ Time Frame: Up to day 29 ]
  32. Incidence of hypersensitivity reactions [ Time Frame: Up to day 29 ]
  33. Incidence of infusion reactions [ Time Frame: Up to day 29 ]
  34. Incidence of gastrointestinal perforation [ Time Frame: Up to day 29 ]
  35. White blood cell count [ Time Frame: Up to day 29 if still hospitalized ]
  36. Hemoglobin levels [ Time Frame: Up to day 29 if still hospitalized ]
  37. Platelet count [ Time Frame: Up to day 29 if still hospitalized ]
  38. Creatinine levels [ Time Frame: Up to day 29 if still hospitalized ]
  39. Total bilirubin level [ Time Frame: Up to day 29 if still hospitalized ]
  40. Alanine aminotransferase (ALT) level [ Time Frame: Up to day 29 if still hospitalized ]
  41. Aspartate aminotransferase (AST) level [ Time Frame: Up to day 29 if still hospitalized ]


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 determined by polymerase chain reaction (PCR), result from any specimen (or other commercial or public health assay) within 2 weeks prior to randomization and no alternative explanation for current clinical condition
  • Hospitalized with illness of any duration with evidence of pneumonia and severe disease, critical disease, multi-system organ dysfunction or immunocompromised at baseline
  • Ability to provide informed consent signed by study patient or legally acceptable representative
  • Willingness and ability to comply with study-related procedures/assessments

Key Exclusion Criteria:

  • In the opinion of the investigator, not expected to survive for more than 48 hours from screening
  • Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count (ANC) less than 2000 mm3, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 5 x upper limit of normal (ULN), platelets <50,000 per mm3
  • Treatment with anti-IL 6, anti-IL-6R antagonists, or with Janus kinase inhibitors (JAKi) in the past 30 days or plans to receive during the study period
  • Current treatment with the simultaneous combination of leflunomide and methotrexate
  • Known active tuberculosis (TB), history of incompletely treated TB, suspected or known extrapulmonary TB, suspected or known systemic bacterial or fungal infections
  • Patients who have received immunosuppressive antibody therapy within the past 5 months, including intravenous immunoglobulin or plans to receive during the study period
  • Participation in a double-blind clinical research study evaluating an investigational product (IP) or therapy within 3 months and less than 5 half-lives of IP prior to the screening visit (The use of remdesivir, hydroxychloroquine, or other treatments being used for COVID-19 treatments in the context of an open-label study or compassionate use protocol is permitted)
  • Any physical examination findings, and/or history of any illness, concomitant medications or recent live vaccines that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study
  • Known systemic hypersensitivity to sarilumab or the excipients of the drug product

NOTE: Other protocol defined inclusion / exclusion criteria may apply


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): NCT04315298


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

Locations
Show Show 63 study locations
Sponsors and Collaborators
Regeneron Pharmaceuticals
Sanofi
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04315298    
Other Study ID Numbers: 6R88-COV-2040
First Posted: March 19, 2020    Key Record Dates
Last Update Posted: April 6, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All 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., FDA, EMA, 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://errs.regeneron.com/external

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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:
COVID-19
SARS-COV-2
coronavirus
IL-6
sarilumab
acute respiratory distress syndrome
treatment