Clinical trial NCT04346797: CORIMUNO19-ECU: Trial Evaluating Efficacy and Safety of Eculizumab (Soliris) in Patients With COVID-19 Infection, Nested in the CORIMUNO-19 Cohort
Official title: CORIMUNO19-ECU: Trial Evaluating Efficacy and Safety of Eculizumab (Soliris) in Patients With COVID-19 Infection, Nested in the CORIMUNO-19 Cohort
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: SARS-CoV-2
COVID19
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-04-15
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Bayesian open labelled randomized clinical trial
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Survival without needs of intubation at day 14
timeFrame: 14 days
measure: Change in organ failure at day 3
timeFrame: 3 days
Secondary outcomes:
measure: Intubation free survival at day 14
timeFrame: Day 14
measure: WHO progression scale at days 4, 7 and 14
timeFrame: 4, 7 and 14 days
measure: Survival at 14, 28 and 90 days
timeFrame: 14, 28 and 90 days
measure: Time to discharge
timeFrame: 90 days
measure: Time to oxygen supply independency
timeFrame: 90 days
measure: Time to negative viral excretion
timeFrame: 90 days
measure: Incidence of secondary infections
timeFrame: 90 days
measure: Vasopressor-free survival
timeFrame: 90 days
measure: Ventilator-free survival
timeFrame: 90 days
measure: 28-day ventilator-free days
timeFrame: 28 days
measure: Incidence of dialysis
timeFrame: 90 days
measure: PaO2/FiO2 ratio
timeFrame: days 4, 7, 14
measure: Rate of respiratory acidosis at day 4
timeFrame: 4 days
measure: Time to ICU discharge
timeFrame: 90 days
Other outcomes:
Locations:
city: Paris
country: France
facility: Saint Louis
state: Ile De France
city: Paris
country: France
facility: Réanimation médicale
city: Paris
country: France
facility: saint Louis
Study officials:
References: