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

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

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.

Study Overview

• Status: Suspended
• Conditions: SARS-CoV-2 Infection; COVID19
• Intervention / Treatment: Drug: Sarilumab; Drug: Azithromycin; Drug: Hydroxychloroquine

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Bobigny, France
    • AP-HP Hopital Avicenne
  • Boulogne-Billancourt, France
    • AP-HP Hopital Ambroise Paré
  • Clichy, France
    • AP-HP Hôpital Beaujon
  • Paris, France
    • AP-HP Hopital Pitie salpetriere
  • Paris, France
    • AP-HP Hopital Saint Antoine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sarilumab + Azithromycin + Hydroxychloroquine; Sarilumab combined with Azithromycin and Hydroxychloroquine	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)
Active Comparator: Sarilumab; Sarilumab only	Drug: Sarilumab; Sarilumab: 400 mg in a 1 hour - I.V. infusion on D1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for ventilation (including invasive and non invasive ventilation), intensive care or death	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.	14 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2020
• Primary Completion (Anticipated): May 8, 2020
• Study Completion (Anticipated): August 1, 2020

Study Registration Dates

• First Submitted: April 6, 2020
• First Submitted That Met QC Criteria: April 9, 2020
• First Posted (Actual): April 10, 2020

Study Record Updates

• Last Update Posted (Actual): May 6, 2020
• Last Update Submitted That Met QC Criteria: May 4, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Azithromycin; Hydroxychloroquine
• Other Study ID Numbers: APHP200375-3

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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