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

COVID19 Clinical Trial

— CORIMUNO19-ECU  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04346797
• Other study ID #: APHP200375-4
• Status: Recruiting
• Phase: Phase 2
• Start date: April 16, 2020
• Est. completion date: December 31, 2020

Study information

• Verified date: April 2020
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Régis Peffault de Latour, MD PhD
• Phone: 1 42 49 96 39
• Email: regis.peffaultdelatour[@]aphp.fr
• 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 31, 2020
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• COVID19
• Infection
• SARS-CoV-2

Intervention

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

Locations

Country	Name	City	State
France	Réanimation médicale	Paris
France	saint Louis	Paris
France	Saint Louis	Paris	Ile De France

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	Survival without needs of intubation at day 14	Survival without needs of intubation, events considered are intubation or death	14 days
Primary	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	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
Secondary	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
Secondary	Survival at 14, 28 and 90 days	Overall survival	14, 28 and 90 days
Secondary	Time to discharge	Time between inclusion and hospital discharge	90 days
Secondary	Time to oxygen supply independency	Time between inclusion and oxygen supply independency	90 days
Secondary	Time to negative viral excretion	Time between inclusion and negative viral excretion	90 days
Secondary	Incidence of secondary infections	Incidence of secondary infections (acquired pneumonia)	90 days
Secondary	Vasopressor-free survival	Vasopressor-free survival	90 days
Secondary	Ventilator-free survival	Ventilator-free survival	90 days
Secondary	28-day ventilator-free days	Number of ventilator-free days alive up to day 28	28 days
Secondary	Incidence of dialysis	Incidence of dialysis (renal replacement therapy)	90 days
Secondary	PaO2/FiO2 ratio	PaO2/FiO2 ratio	days 4, 7, 14
Secondary	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
Secondary	Time to ICU discharge	Time to ICU discharge	90 days