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

NCT04341870 | Suspended Phase 2 DMC

• 1 other identifier: APHP200375-3
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

COVID19; SARS-CoV-2 Infection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Early improvement: OMS progression scale <= 5

  4 days

• OMS progression scale

  4, 7 and 14 days

• Survival

  14, 28 and 90 days

• ICU-free days alive

  14, 28 and 90 days

• Ventilation-free days alive

  14 and 28 days

Study Arms (2)

Sarilumab + Azithromycin + Hydroxychloroquine

EXPERIMENTAL

Sarilumab combined with Azithromycin and Hydroxychloroquine

Drug: Sarilumab; Drug: Azithromycin; Drug: Hydroxychloroquine

Sarilumab

ACTIVE COMPARATOR

Sarilumab only

Drug: Sarilumab

Interventions

Sarilumab DRUG

Sarilumab: 400 mg in a 1 hour - I.V. infusion on D1

Sarilumab; Sarilumab + Azithromycin + Hydroxychloroquine

Azithromycin DRUG

Azithromycin: oral administration, 500mg on D1 then 250mg QD on D2 to D5 (total duration 5 days)

Sarilumab + Azithromycin + Hydroxychloroquine

Hydroxychloroquine DRUG

Hydroxychloroquine: oral administration, 600mg QD (200mg TID) from D1 to D10 (total duration 10 days)

Sarilumab + Azithromycin + Hydroxychloroquine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \[PaO2/FiO2 ≤ 300mmHg\]

You may not qualify if:

• Respiratory failure requiring non invasive or mechanical ventilation
• Patients requiring intensive care
• Do-not-resuscitate order (DNR order)
• Known hypersensitivity to sarilumab or to any of their excipients.
• Known contra-indication to hydroxychloroquine or chloroquine: including hypersensitivity/allergy, retinopathy, G6PD deficiency and QT prolongation
• Known contra-indication to azithromycin: including hypersensitivity/allergy and QT prolongation
• Pregnancy or breastfeeding
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (5)

AP-HP Hôpital Avicenne

Bobigny, France

Location

AP-HP Hôpital Ambroise Paré

Boulogne-Billancourt, France

Location

AP-HP Hôpital Beaujon

Clichy, France

Location

AP-HP Hôpital Pitié Salpétrière

Paris, France

Location

AP-HP Hôpital Saint Antoine

Paris, France

Location

MeSH Terms

Conditions

COVID-19

Interventions

sarilumab; Azithromycin; Hydroxychloroquine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Bayesian open labelled randomized clinical trial

Study Record Dates

• First Submitted: April 6, 2020
• First Posted: April 10, 2020
• Study Start: April 11, 2020
• Primary Completion: May 8, 2020
• Study Completion: August 1, 2020
• Last Updated: May 6, 2020

Record last verified: 2020-04

Locations

FR (5)