Study of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients: Sarilumab, Azithromycin, Hydroxychloroquine Trial – CORIMUNO-19 – VIRO

Overview

The overall objective of the study is to determine the therapeutic effect and tolerance of Sarilumab in combination with Azithromycin and Hydroxychloroquine, compared to Sarilumab only, patients with moderate, severe 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 investigational treatments administration to patients enrolled in the CORIMUNO-19 cohort (NCT04324047). Sarilumab+Azithromycin+Hydroxychloroquine, or Sarilumab only will be administered to consenting adult patients hospitalized with COVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation. All patients will receive standard of care along with randomized investigational treatments. Outcomes of included patients will be compared between groups as well as with outcomes of patients in the CORIMUNO-19 cohort treated with other immune modulators or standard of care.

Full Title of Study: “Efficacy of Sarilumab + Azithromycin + Hydroxychloroquine, and Sarilumab Alone, for Adult Patients Hospitalized With Moderate to Severe COVID-19: a Multicenter Open-label 1:1 Randomized Controlled Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: May 8, 2020

Interventions

  • Drug: Sarilumab
    • Sarilumab: 400 mg in a 1 hour – I.V. infusion on D1
  • Drug: Azithromycin
    • Azithromycin: oral administration, 500mg on D1 then 250mg QD on D2 to D5 (total duration 5 days)
  • Drug: Hydroxychloroquine
    • Hydroxychloroquine: oral administration, 600mg QD (200mg TID) from D1 to D10 (total duration 10 days)

Arms, Groups and Cohorts

  • Experimental: Sarilumab + Azithromycin + Hydroxychloroquine
    • Sarilumab combined with Azithromycin and Hydroxychloroquine
  • Active Comparator: Sarilumab
    • Sarilumab only

Clinical Trial Outcome Measures

Primary Measures

  • Need for ventilation (including invasive and non invasive ventilation), intensive care or death
    • Time Frame: 14 days
    • Events considered are: need for ventilation (including invasive and non invasive ventilation), transfer to the Intensive Care Unit, death or new do-not-resuscitate (DNR) decision in the absence ventilation and outside ICU.

Secondary Measures

  • Early improvement: OMS progression scale <= 5
    • Time Frame: 4 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
  • OMS progression scale
    • Time Frame: 4, 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
  • Survival
    • Time Frame: 14, 28 and 90 days
    • Overall survival
  • ICU-free days alive
    • Time Frame: 14, 28 and 90 days
    • Number of ICU-free days alive
  • Ventilation-free days alive
    • Time Frame: 14 and 28 days
    • Number of ventilation(invasive or non invasive)-free days alive
  • Hospital-free days alive
    • Time Frame: 14, 28 and 90 days
    • Number of hospital-free days alive
  • Oxygen therapy-free days alive
    • Time Frame: 14 and 28 days
    • Number of oxygen therapy-free days alive
  • Time to negative viral excretion
    • Time Frame: 90 days
    • SARS-CoV-2 viral load measurement by rtPCR
  • Immunophenotyping and multiplex cytokines
    • Time Frame: 8 days
    • Immunophenotyping and multiplex cytokines (blood sample)

Participating in This Clinical Trial

Inclusion Criteria

  • Patients included in the CORIMUNO-19 cohort (NCT04324047) – COVID-19 cases not requiring ICU at admission with moderate or severe pneumopathy according to the WHO 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] AND [Requiring between 3L/min and 5L/min of oxygen to maintain SpO2>97%] OR – Severe cases: Cases meeting any of the following criteria: [Respiratory distress ( ≥ 30 breaths/ min)] OR [Oxygen saturation≤93% at rest in ambient air; or Oxygen saturation ≤97 % with O2 > 5L/min] OR [PaO2/FiO2 ≤ 300mmHg] Exclusion Criteria:
  • 1. Patients with exclusion criteria to the CORIMUNO-19 cohort. 2. Respiratory failure requiring non invasive or mechanical ventilation 3. Patients requiring intensive care 4. Do-not-resuscitate order (DNR order) 5. Known hypersensitivity to sarilumab or to any of their excipients. 6. Known contra-indication to hydroxychloroquine or chloroquine: including hypersensitivity/allergy, retinopathy, G6PD deficiency and QT prolongation 7. Known contra-indication to azithromycin: including hypersensitivity/allergy and QT prolongation 8. Pregnancy or breastfeeding 9. Current documented bacterial infection. 10. 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
  • Gender Eligibility: All

    Minimum Age: 18 Years

    Maximum Age: 80 Years

    Are Healthy Volunteers Accepted: No

    Investigator Details

    • Lead Sponsor
      • Assistance Publique – Hôpitaux de Paris
    • Provider of Information About this Clinical Study
      • Sponsor

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