CORIMUNO19-ECU: Trial Evaluating Efficacy and Safety of Eculizumab (Soliris) in Patients With COVID-19 Infection, Nested in the CORIMUNO-19 Cohort (CORIMUNO19-ECU)

The overall objective of the study is to determine the therapeutic effect and tolerance of Eculizumab in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Eculizumab is a terminal complement inhibitor that has been investigated for more than 10 years in numerous complement-mediated diseases. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Eculizumab administration to patients enrolled in the CORIMUNO-19 cohort. Eculizumab 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 Eculizumab will receive standard of care. Outcomes of Eculizumab-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.

Study Overview

• Status: Unknown
• Conditions: SARS-CoV-2; COVID19
• Intervention / Treatment: Drug: Eculizumab

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • Recruiting
    • Saint Louis
    • Contact: R Peffault de la Tour, MD; Phone Number: 33(1)42494949
    • Principal Investigator: Regis Peffault de la Tour, MD
  • Paris, France, 75010
    • Recruiting
    • Réanimation médicale
    • Contact: Elie Azoulay, MD PhD
  • Ile De France
    • Paris, Ile De France, France, 75010
      • Recruiting
      • Saint Louis
      • Contact: Anne Bergeron-Lafaurie, MD PhD; Phone Number: +33 1 42 49 41 66; Email: anne.bergeron-lafaurie@aphp.fr
      • Principal Investigator: Anne bergeron-Lafaurie, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients between 18 and 675 years old included in the CORIMUNO-19 cohort

2. Patients belonging to one of the 2 following groups

   • Group 1: 60 patients not requiring ICU at admission with moderate and severe pneumopathy according to the WHO Criteria of severity of COVID pneumopathy, meeting all of the 2 following criteria:

     • Respiratory symptoms with radiological findings of pneumonia
     • Severe pneumonia requiring ≥ 5L/min of oxygen to maintain SpO2 >97%

   • Group 2: 60 patients requiring ICU based on Criteria of severity of COVID pneumopathy.

     • Respiratory failure and requiring mechanical ventilation
     • Vasopressive support
3. Vaccinated against meningococcal infections within 3 years prior to, or at the time of, initiating Eculizumab to reduce the risk of meningococcal infection (N meningitidis) [(Bexsero® (2 injections with a minimum of 1 month interval) + Menveo@ or Niminrex® ) and daily antibiotics (Oracilline®)]. If vaccination cannot be confirmed or if the patient cannot receive it, the participant should receive prophylactic antibiotics against meningococcal infection prior to initiating Eculizumab treatment and for at least 3 months from the last infusion of Eculizumab.
4. Female patients of childbearing potential and male patients with female partners of childbearing potential must follow protocol-specified guidance for avoiding pregnancy while on treatment and for 8 months after last dose of Eculizumab.

5- Body weight ≥40 kg

6-Patient and/or alternatively by next-of-kin must be willing and able to give written informed consent according to the applicable regulations including emergency and intensive care contexts

Exclusion Criteria:

• Patients with exclusion criteria to the CORIMUNO-19 cohort.
• Age ≥ 70 years
• Pregnancy or lactation
• History or unresolved Neisseria meningiditis infection
• Ongoing sepsis, presence or suspicion of active and untreated systemic bacterial infection prior study screening and untreated with antibiotics,
• Hypersensitivity to any ingredient contained in Eculizumab, including hypersensitivity to murine proteins.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Eculizumab	Drug: Eculizumab; Intravenous administration as follows: Induction dosage regimen at 1200 mg on Days 1, 4, 8 then 1200 mg or 900 mg on Day 12 depending on the monitoring of Eculizumab Plasma Level and CH5O and sC5B9 and maintenance doses of 900 mg on Days 15, 18 and 22
NO_INTERVENTION: Standard of Care; Best standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival without needs of intubation at day 14	Survival without needs of intubation, events considered are intubation or death	14 days
Change in organ failure at day 3	Change in organ failure at day 3, defined by the relative variation in Sequential Organ Failure Assessment score	3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intubation free survival at day 14	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	Day 14
WHO progression scale at days 4, 7 and 14	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
Survival at 14, 28 and 90 days	Overall survival	14, 28 and 90 days
Time to discharge	Time between inclusion and hospital discharge	90 days
Time to oxygen supply independency	Time between inclusion and oxygen supply independency	90 days
Time to negative viral excretion	Time between inclusion and negative viral excretion	90 days
Incidence of secondary infections	Incidence of secondary infections (acquired pneumonia)	90 days
Vasopressor-free survival	Vasopressor-free survival	90 days
Ventilator-free survival	Ventilator-free survival	90 days
28-day ventilator-free days	Number of ventilator-free days alive up to day 28	28 days
Incidence of dialysis	Incidence of dialysis (renal replacement therapy)	90 days
PaO2/FiO2 ratio	PaO2/FiO2 ratio	days 4, 7, 14
Rate of respiratory acidosis at day 4	Number of patients with arterial blood pH of <7.25, with a partial pressure of arterial carbon dioxide [Paco2] of ≥60 mm Hg for >6 hours	4 days
Time to ICU discharge	Time to ICU discharge	90 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 16, 2020
• Primary Completion (ANTICIPATED): September 30, 2020
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: April 6, 2020
• First Submitted That Met QC Criteria: April 10, 2020
• First Posted (ACTUAL): April 15, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 27, 2020
• Last Update Submitted That Met QC Criteria: April 23, 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; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Eculizumab
• Other Study ID Numbers: APHP200375-4

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