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Sarilumab COVID-19

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ClinicalTrials.gov Identifier: NCT04327388
Recruitment Status : Completed
First Posted : March 31, 2020
Last Update Posted : September 9, 2020
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE March 26, 2020
First Posted Date  ICMJE March 31, 2020
Last Update Posted Date September 9, 2020
Actual Study Start Date  ICMJE March 28, 2020
Actual Primary Completion Date July 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 9, 2020)
Time to improvement of 2 points in clinical status assessment from baseline using the 7-point ordinal scale [ Time Frame: Baseline to Day 29 ]
The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Original Primary Outcome Measures  ICMJE
 (submitted: March 26, 2020)
  • Phase 2: Time to resolution of fever for at least 48 hours without antipyretics or until discharge, whichever is sooner [ Time Frame: Baseline to Day 29 ]
    Resolution of fever is defined as body temperature: ≤36.6 C (axilla) or ≤37.2 C (oral), or ≤37.8 C (rectal or tympanic).
  • Phase 3: The percentage of patients reporting each severity rating on the 7-point ordinal scale [ Time Frame: Baseline to Day 15 ]
    The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 9, 2020)
  • Percent of patients alive at Day 29 [ Time Frame: Day 29 ]
  • Proportion of patients with one point improvement from baseline in clinical status assessment at days 4, 7, 15, 21, 29 using the 7-point ordinal scale [ Time Frame: Baseline to Days 4, 7, 15, 21, 29 ]
    The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
  • Mean change in the 7-point ordinal scale from baseline to Days 4, 7, 15, 21, and 29 (or until discharge) [ Time Frame: Baseline to Days 4, 7, 15, 21, 29 (or until discharge) ]
    The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
  • Time to resolution of fever [ Time Frame: Baseline to Day 29 ]
    Defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner.
  • Time to resolution of fever and improvement in oxygenation [ Time Frame: Baseline to Day 29 ]
    Resolution of both fever and improvement in oxygenation. Resolution of fever is defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner. Improvement in oxygenation is defined as SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours, or until discharge, whichever is sooner.
  • Days with fever [ Time Frame: Baseline to Day 29 ]
    Fever is defined as >37.4°C (axilla), or >38.0 °C (oral), or >38.4°C (rectal or tympanic) based on maximum value observed during a 24-hour period.
  • Time to change in NEWS2 from baseline [ Time Frame: Baseline to Day 29 ]
    The National Early Warning Score (NEWS2) is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
  • Time to NEWS2 of <2 and maintained for 24 hours [ Time Frame: Baseline to Day 29 ]
    The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
  • Mean change from baseline to days 4, 7, 15, 21, and 29 in NEWS2 [ Time Frame: Baseline to days 4, 7, 15, 21, and 29 ]
    The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
  • Time-to-improvement in oxygenation [ Time Frame: Baseline to Day 29 ]
    SpO2/FiO2 of 50 or greater compared to the nadir for at least 48 hours, or until discharge, whichever is sooner. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.
  • Alive off supplemental oxygen at day 29 [ Time Frame: Day 29 ]
    Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.
  • Days of hypoxemia [ Time Frame: Baseline to Day 29 ]
    Hypoxemia is defined as SpO2 <93% on room air, or requiring supplemental oxygen, or mechanical ventilatory support.
  • Days of supplemental oxygen use [ Time Frame: Baseline to Day 29 ]
    Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.
  • Days of resting respiratory rate >24 breaths/min [ Time Frame: Baseline to Day 29 ]
  • Time to saturation ≥94% on room air [ Time Frame: Baseline to Day 29 ]
  • Ventilator free days in the first 28 days (to day 29) [ Time Frame: Baseline to Day 29 ]
  • The number of patients with Initiation of mechanical ventilation, non-invasive ventilation, or use of high flow nasal cannula [ Time Frame: Baseline to Day 60 ]
    For those not requiring these interventions at baseline.
  • Proportion of patients requiring rescue medication during the 28-day period [ Time Frame: Baseline to Day 28 ]
  • The number of patients transferred to the ICU or the need to transfer to the ICU (if the ICU is not available) [ Time Frame: Baseline to Day 60 ]
    For patients are not in ICU at baseline
  • Days of hospitalization among survivors [ Time Frame: Baseline to Day 60 ]
  • Incidence of serious adverse events [ Time Frame: Baseline to Day 60 ]
  • The incidence of major or opportunistic bacterial or fungal infections [ Time Frame: Baseline to Day 60 ]
  • The incidence of major or opportunistic bacterial or fungal infections in patients with grade 4 neutropenia [ Time Frame: Baseline to Day 60 ]
  • The incidence of hypersensitivity reactions, infusion reactions, gastrointestinal perforation [ Time Frame: Baseline to Day 60 ]
  • The number of patients with clinically significant laboratory abnormalities [ Time Frame: Baseline to Day 60 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2020)
  • Phase 2: The time to improvement in oxygenation [ Time Frame: Baseline to Day 29 ]
    Increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.
  • Phase 2: Mean change in 7-point ordinal scale from baseline to Day 15 [ Time Frame: Baseline to Day 15 ]
    The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
  • Phase 2: Clinical status using the 7-point ordinal scale at Day 15 [ Time Frame: Baseline to Day 15 ]
    The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
  • Phase 2: Time to improvement of two categories from admission using the 7-point ordinal scale [ Time Frame: Baseline to Day 29 ]
    The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
  • Phase 2 and 3 : Time to resolution of fever [ Time Frame: Baseline to Day 29 ]
    Defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner.
  • Phase 2 and 3 : Time to improvement in oxygenation [ Time Frame: Baseline to Day 29 ]
    Increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2) for at least 48 hours, or until discharge, whichever is sooner. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.
  • Phase 2 and 3: Time to resolution of fever and improvement in oxygenation [ Time Frame: Baseline to Day 29 ]
    Resolution of both fever and improvement in oxygenation. Resolution of fever is defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner. Improvement in oxygenation is increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2) for at least 48 hours, or until discharge, whichever is sooner. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.
  • Phase 2 and 3:Time to change in NEWS2 from baseline [ Time Frame: Baseline to Day 29 ]
    The National Early Warning Score (NEWS2) is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
  • Phase 2 and 3: Time to NEWS2 of <2 and maintained for 24 hours [ Time Frame: Baseline to Day 29 ]
    The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
  • Phase 2 and 3: Mean change from baseline to days 3, 5, 8, 11, 15, and 29 in NEWS2 [ Time Frame: Baseline to days 3, 5, 8, 11, 15, and 29 ]
    The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
  • Phase 2 and 3:Days with fever [ Time Frame: Baseline to Day 29 ]
    Fever is defined as >37.4°C (axilla), or >38.0 °C (oral), or >38.4°C (rectal or tympanic) based on maximum value observed during a 24 period.
  • Phase 2 and 3: Alive off supplemental oxygen at day 29 [ Time Frame: Baseline to Day 29 ]
    Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.
  • Phase 2 and 3: Days of resting respiratory rate >24 breaths/min [ Time Frame: Baseline to Day 29 ]
  • Phase 2 and 3:Days of hypoxemia [ Time Frame: Baseline to Day 29 ]
    Hypoxemia is defined as SpO2 <93% on room air, or requiring supplemental oxygen, or mechanical ventilatory support.
  • Phase 2 and 3: Days of supplemental oxygen use [ Time Frame: Baseline to Day 29 ]
    Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.
  • Phase 2 and 3: Time to saturation ≥94% on room air [ Time Frame: Baseline to Day 29 ]
  • Phase 2 and 3: Ventilator free days in the first 28 days (to day 29) [ Time Frame: Baseline to Day 29 ]
  • Phase 2 and 3: The number of patients with Initiation of mechanical ventilation, non-invasive ventilation, or use of high flow nasal cannula [ Time Frame: Baseline to Day 60 ]
    For those not requiring these interventions at baseline.
  • Phase 2 and 3: Proportion of patients requiring rescue medication during the 28-day period [ Time Frame: Baseline to Day 28 ]
  • Phase 2 and 3: The number of patients transferred to the ICU or the need to transfer to the ICU (if the ICU is not available) [ Time Frame: Baseline to Day 60 ]
    For patients are not in ICU at baseline
  • Phase 2 and 3: Days of hospitalization among survivors [ Time Frame: Baseline to Day 60 ]
  • Phase 2 and 3: Incidence of death [ Time Frame: Baseline to Day 60 ]
  • Phase 3: Mean change in the 7-point ordinal scale from baseline to days 3, 5, 8, 11, 15, and 29 (or until discharge) [ Time Frame: baseline to days 3, 5, 8, 11, 15, and 29 (or until discharge) ]
    The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
  • Phase 3: Clinical status using the 7-point ordinal scale at days 3, 5, 8, 11,15, and 29 [ Time Frame: Days 3, 5, 8, 11,15, and 29 ]
    The ordinal scale is an assessment of the clinical status. Scores range 1-7. Lower score is worse.
  • Phase 3: Time to improvement of two categories from admission using the 7-point ordinal scale [ Time Frame: Baseline to Day 29 ]
    The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
  • Phase 2 and 3: Incidence of serious adverse events [ Time Frame: Baseline to Day 60 ]
  • Phase 2 and 3: The incidence of major or opportunistic bacterial or fungal infections [ Time Frame: Baseline to Day 60 ]
  • Phase 2 and 3: The incidence of major or opportunistic bacterial or fungal infections in patients with grade 4 neutropenia [ Time Frame: Baseline to Day 60 ]
  • Phase 2 and 3: The incidence of hypersensitivity reactions, infusion reactions, gastrointestinal perforation [ Time Frame: Baseline to Day 60 ]
  • The number of patients with clinically significant laboratory abnormalities [ Time Frame: Baseline to Day 60 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sarilumab COVID-19
Official Title  ICMJE An Adaptive Phase 3, Randomized, Double-blind, Placebo-controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID19
Brief Summary

Primary Objective:

To evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with severe or critical COVID-19

Secondary Objectives:

  • Evaluate the 28-day survival rate
  • Evaluate the clinical efficacy of sarilumab compared to the control arm by clinical severity
  • Evaluate changes in the National Early Warning Score 2 (NEWS2)
  • Evaluate the duration of predefined symptoms and signs (if applicable)
  • Evaluate the duration of supplemental oxygen dependency (if applicable)
  • Evaluate the incidence of new mechanical ventilation use during the study
  • Evaluate the duration of new mechanical ventilation use during the Study
  • Evaluate the proportion of patients requiring rescue medication during the 28-day period
  • Evaluate need for admission into intensive care unit (ICU)
  • Evaluate duration of hospitalization (days)
  • The secondary safety objectives of the study are to evaluate the safety of sarilumab through hospitalization (up to day 29 if patient is still hospitalized) compared to the control arm as assessed by incidence of:

    • Serious adverse events (SAEs)
    • Major or opportunistic bacterial or fungal infections in patients with grade 4 neutropenia
    • Grade ≥2 infusion related reactions
    • Grade ≥2 hypersensitivity reactions
    • Increase in alanine transaminase (ALT) ≥3X upper limit of normal (ULN) (for patients with normal baseline) or >3X ULN AND at least 2-fold increase from baseline value (for patients with abnormal baseline)
    • Major or opportunistic bacterial or fungal infections
Detailed Description An individual patient will complete the study approximately 60 days from screening to follow-up on day 60 ±7 days.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Corona Virus Infection
Intervention  ICMJE
  • Drug: Sarilumab SAR153191
    Pharmaceutical form:Solution for injection Route of administration: Intravenous infusion
    Other Name: REGN88
  • Drug: Placebo
    Pharmaceutical form:Solution for injection Route of administration: Intravenous infusion
Study Arms  ICMJE
  • Experimental: Sarilumab Dose 1
    Sarilumab Dose 1 given intravenously one time on Day 1. Patients may receive a second dose with Sarilumab Dose 1 24 to 48 hours after the first dose.
    Intervention: Drug: Sarilumab SAR153191
  • Experimental: Sarilumab Dose 2
    Sarilumab Dose 2 given intravenously one time on Day 1. Patients may receive a second dose with Sarilumab Dose 2 24 to 48 hours after the first dose.
    Intervention: Drug: Sarilumab SAR153191
  • Placebo Comparator: Matching placebo
    Matching placebo given intravenously one time on Day 1. Patients may receive a second dose with matching placebo 24 to 48 hours after the first dose.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 7, 2020)
421
Original Estimated Enrollment  ICMJE
 (submitted: March 26, 2020)
300
Actual Study Completion Date  ICMJE August 31, 2020
Actual Primary Completion Date July 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria :

Participants must be ≥18 years of age Participants must be hospitalized for less than or equal to 7 days with evidence of pneumonia and have one of the following disease categories: severe disease or critical disease Laboratory-confirmed SARS-CoV-2 infection

Exclusion criteria:

Unlikely to survive after 48 hours from screening or unlikely to remain at the investigational site beyond 48 hours. Patients with multi organ dysfunction or requiring extracorporeal life support or renal replacement therapy are excluded.

Presence of neutropenia less than 2000/mmˆ3, AST or ALT greater than 5 X ULN, platelets less than 50,000/mmˆ3 Prior immunosuppressive therapies Use of systemic chronic corticosteroids for non-COVID-19 related condition Known or suspected history of tuberculosis Suspected or known active systemic bacterial or fungal infections

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Brazil,   Canada,   Chile,   France,   Germany,   Israel,   Italy,   Japan,   Russian Federation,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04327388
Other Study ID Numbers  ICMJE EFC16844
2020-001162-12 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Regeneron Pharmaceuticals
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP