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

COVID19 Clinical Trial

— CORIMUNO-VIRO  

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04341870
• Other study ID #: APHP200375-3
• Status: Suspended
• Phase: Phase 2/Phase 3
• Start date: April 11, 2020
• Est. completion date: August 2020

Study information

• Verified date: April 2020
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 27
• Est. completion date: August 2020
• Est. primary completion date: May 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID19
• SARS-CoV-2 Infection

Intervention

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

Locations

Country	Name	City	State
France	AP-HP Hôpital Avicenne	Bobigny
France	AP-HP Hôpital Ambroise Paré	Boulogne-Billancourt
France	AP-HP Hôpital Beaujon	Clichy
France	AP-HP Hôpital Pitié Salpétrière	Paris
France	AP-HP Hôpital Saint Antoine	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Survival	Overall survival	14, 28 and 90 days
Secondary	ICU-free days alive	Number of ICU-free days alive	14, 28 and 90 days
Secondary	Ventilation-free days alive	Number of ventilation(invasive or non invasive)-free days alive	14 and 28 days
Secondary	Hospital-free days alive	Number of hospital-free days alive	14, 28 and 90 days
Secondary	Oxygen therapy-free days alive	Number of oxygen therapy-free days alive	14 and 28 days
Secondary	Time to negative viral excretion	SARS-CoV-2 viral load measurement by rtPCR	90 days
Secondary	Immunophenotyping and multiplex cytokines	Immunophenotyping and multiplex cytokines (blood sample)	8 days