Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients - Sarilumab Trial - CORIMUNO-19 - SARI (CORIMUNO-SARI)

The overall objective of the study is to determine the therapeutic effect and tolerance of Sarilumab in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Sarilumab is a human IgG1 monoclonal antibody that binds specifically to both soluble and membrane-bound IL-6Rs (sIL-6Rα and mIL-6Rα) and has been shown to inhibit IL-6-mediated signaling through these receptors. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Sarilumab administration to patients enrolled in the CORIMUNO-19 cohort. Sarilumab will be administered to consenting adult patients hospitalized with COVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. Patients who will chose not to receive Sarilumab will receive standard of care. Outcomes of Sarilumab-treated patients will be compared with outcomes of standard of care-treated patients as well as with outcomes of patients treated with other immune modulators.

Study Overview

• Status: Completed
• Conditions: Corona Virus Infection
• Intervention / Treatment: Drug: Sarilumab

• Study Type: Interventional
• Enrollment (Actual): 239
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75005
    • Necker Hospital
  • Ile De France
    • Le Kremlin-Bicêtre, Ile De France, France
      • Kremlin Bicetre hospital APHP
    • Paris, Ile De France, France
      • Cochin Aphp
    • Paris, Ile De France, France
      • HEGP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients included in the CORIMUNO-19 cohort

2. Patients belonging to one of the 2 following groups:

   • Group 1: patients not requiring Intensive Care Unit at admission with moderate and severe pneumopathy according to the OMS Criteria of severity of COVID pneumopathy.

Moderate cases :

Cases meeting all of the following criteria:

• Showing fever and respiratory symptoms with radiological findings of pneumonia.
• Requiring between 3L/min and 5L/min of oxygen to maintain SpO2 >97% Severe cases

Cases meeting any of the following criteria:

• Respiratory distress (≧30 breaths/ min);
• Oxygen saturation≤93% at rest in ambient air; or Oxygen saturation ≤97 % with O2 > 5L/min.
• PaO2/FiO2≦300mmHg
• Group 2: patients requiring Intensive Care Unit based on Criteria of severity of COVID pneumopathy.
• Respiratory failure and requiring mechanical ventilation
• No do-not-resuscitate order (DNR order)

Exclusion Criteria:

• Patients with exclusion criteria to the CORIMUNO-19 cohort.
• Known hypersensitivity to Sarilumab or to any of their excipients.
• Pregnancy
• Current documented bacterial infection
• Patient with any of following laboratory results out of the ranges detailed below at screening should be discussed depending of the medication:
• Absolute neutrophil count (ANC) ≤ 1.0 x 109/L
• Haemoglobin level: no limitation
• Platelets (PLT) < 50 G /L
• SGOT or SGPT > 5N

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SARILUMAB -- Severe COVID population (WHO Clinical Progression Scale =5 at baseline); Sarilumab (an IV dose of 400 mg of sarilumab in a 1 hour-infusion at Day 1). Administration of Sarilumab fixed dose on day 3 was recommended and left to the treating physician	Drug: Sarilumab; (an IV dose of 400 mg of sarilumab in a 1 hour-infusion at D1
No Intervention: Standard of care -- Severe COVID population (WHO Clinical Progression Scale =5 at baseline); Usual care was provided at the discretion of the clinicians
Experimental: SARILUMAB -- Critical COVID population (WHO Clinical Progression Scale >5 at baseline); Sarilumab (an IV dose of 400 mg of sarilumab in a 1 hour-infusion at Day 1). Administration of Sarilumab fixed dose on day 3 was recommended and left to the treating physician	Drug: Sarilumab; (an IV dose of 400 mg of sarilumab in a 1 hour-infusion at D1
No Intervention: Standard of care -- Critical COVID population (WHO Clinical Progression Scale >5); Usual care was provided at the discretion of the clinicians

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With WHO Clinical Progression Scale > 5 at Day 4 -- Severe COVID Population (WHO Clinical Progression Scale =5 at Baseline)	Percentage of participants who has died or needed non-invasive or mechanical ventilation by day 4 (WHO clinical progression scale > 5). A patient with new do-not-resuscitate order at day 4 will be considered as with a score > 5. WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10	4 days
Percentage of Participants With Non-invasive Ventilation, Mechanical Ventilation or Death at Day 14 (WHO Clinical Progression Scale =5 at Baseline)	Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Percentage of non-invasive ventilation, mechanical ventilation or death. Thus, events considered are needing ventilator utilization (mechanical or non-invasive ventilation including high flow oxygen), or death. New do-not-resuscitate (DNR) order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.	Day 1 to Day 14
Cumulative Incidence (Percentage of Participants) With Successful Tracheal Extubation at Day 14 -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)	Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of Non Invasive Ventilation or high flow (for > 48h) if they were included under oxygen by Non Invasive Ventilation or High flow (score 6) and remained without intubation. Death or new do-not-resuscitate order (if given after the inclusion of the patient) will be considered as a competing event.	Day 1 to Day 14
Percentage of Participants With no Improvement in WHO Clinical Progression Scale at Day 4 -- Critical COVID Population ( WHO Clinical Progression Scale >5 at Baseline)	Results are presented as the percentage not improved, so that an effective treatment would be associated with a decrease in percentage Scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9	4 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Surviving (Overall Survival)	Percentage of participants surviving at 14, 28 and 90 days	14, 28 and 90 days
WHO Progression Scale	WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10	4, 7 and 14 days
Mean of Ventilator Free-days at Day 28 -- Critical COVID Population (WHO-clinical Progression Scale >5 at Baseline)	28-day ventilator free-days	28 days
Cumulative Incidence (Percentage of Participants) of Discharge From Hospital	Time to discharge from hospital	28, 90 days
Cumulative Incidence (Percentage of Participants) of Intensive Care Unit Discharge -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)	Time to discharge from Intensive Care Unit	28, 90 days
Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency	Time to oxygen supply independency	28, 90 days
PaO2/FiO2 Ratio -- Critical COVID Population (WHO-CPS >5)	evolution of PaO2/FiO2 ratio PaO2 is partial pressure of arterial oxygen expressed in mmHg. FiO2 is fraction of inspired oxygen (for instance, 0.33 for 33% oxygen) with no units. PaO2/FiO2 ratio is expressed in mmHg.	day 1 to day 14

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Hermine O, Mariette X, Porcher R, Resche-Rigon M, Tharaux PL, Ravaud P; CORIMUNO-19 Collaborative Group. Effect of interleukin-6 receptor antagonists in critically ill adult patients with COVID-19 pneumonia: two randomised controlled trials of the CORIMUNO-19 Collaborative Group. Eur Respir J. 2022 Aug 10;60(2):2102523. doi: 10.1183/13993003.02523-2021. Print 2022 Aug.
• CORIMUNO-19 Collaborative group. Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial. Lancet Rheumatol. 2022 Jan;4(1):e24-e32. doi: 10.1016/S2665-9913(21)00315-5. Epub 2021 Nov 17.

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2020
• Primary Completion (Actual): April 21, 2020
• Study Completion (Actual): September 24, 2020

Study Registration Dates

• First Submitted: March 25, 2020
• First Submitted That Met QC Criteria: March 25, 2020
• First Posted (Actual): March 27, 2020

Study Record Updates

• Last Update Posted (Actual): June 12, 2025
• Last Update Submitted That Met QC Criteria: June 11, 2025
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; RNA Virus Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; Coronavirus Infections
• Other Study ID Numbers: APHP200375-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No