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)

• ClinicalTrials.gov Identifier: NCT04324073
• Recruitment Status: Active, not recruiting
• First Posted: March 27, 2020
• Last Update Posted: April 15, 2020
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Corona Virus Infection	Drug: Sarilumab	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 239 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Bayesian open labelled randomized clinical trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients - Sarilumab Trial - CORIMUNO-19 - SARI
• Actual Study Start Date: March 27, 2020
• Estimated Primary Completion Date: March 27, 2021
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: SARILUMAB; Sarilumab (an IV dose of 400 mg of sarilumab in a 1 hour-infusion at D1).	Drug: Sarilumab; (an IV dose of 400 mg of sarilumab in a 1 hour-infusion at D1
No Intervention: Standard of care; best standard of care

Outcome Measures

Primary Outcome Measures :

1. Survival without needs of ventilator utilization at day 14. [ Time Frame: 14 days ]
   Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Thus, events considered are needing ventilator utilization (including Non Invasive Ventilation, NIV or high flow), or death. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.
2. WHO progression scale <=5 at day 4 [ Time Frame: 4 days ]

   Proportion of patients alive without non-invasive ventilation of high low at day 4 (WHO progression scale ≤ 5). A patient with new DNR 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

3. Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 [ Time Frame: 14 days ]
   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 NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event.
4. WHO progression scale at day 4 [ Time Frame: 4 days ]

   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 NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event.

   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

Secondary Outcome Measures :

1. WHO progression scale [ Time Frame: 7 and 14 days ]

   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

2. Survival [ Time Frame: 14, 28 and 90 days ]
   Overall survival
3. 28-day ventilator free-days [ Time Frame: 28 days ]
4. respiratory acidosis at day 4 [ Time Frame: 4 days ]
   arterial blood pH of <7.25 with a partial pressure of arterial carbon dioxide [Paco2] of ≥60 mm Hg for >6 hours
5. PaO2/FiO2 ratio [ Time Frame: day 1 to day 14 ]
   evolution of PaO2/FiO2 ratio
6. time to oxygen supply independency [ Time Frame: 14 days ]
   time to oxygen supply independency
7. duration of hospitalization [ Time Frame: 90 days ]
   duration of hospitalization
8. time to negative viral excretion [ Time Frame: 90 days ]
   time to negative viral excretion
9. time to ICU discharge [ Time Frame: 90 days ]
   time to ICU discharge
10. time to hospital discharge [ Time Frame: 90 days ]
    time to hospital discharge

Eligibility Criteria

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

Criteria

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 ICU 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 ICU 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

Contacts and Locations

Locations

France

Kremlin Bicetre hospital APHP

Le Kremlin-Bicêtre, Ile De France, France

Cochin Aphp

Paris, Ile De France, France

HEGP

Paris, Ile De France, France

NECKER Hospital

Paris, France, 75005

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

More Information

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT04324073
• Other Study ID Numbers: APHP200375-2
• First Posted: March 27, 2020
• Last Update Posted: April 15, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Coronavirus Infections; Severe Acute Respiratory Syndrome; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Respiratory Tract Infections; Respiratory Tract Diseases