Back to resultsCORIMUNO19-ECU: Trial Evaluating Efficacy and Safety of Eculizumab (Soliris) in Patients With COVID-19 Infection, Nested in the CORIMUNO-19 Cohort (CORIMUNO19-ECU)
Primary Purpose
SARS-CoV-2, COVID19
Status
Unknown status
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Eculizumab
Sponsored by
About this trial
This is an interventional treatment trial for SARS-CoV-2
Eligibility Criteria
Inclusion Criteria:
- Patients between 18 and 675 years old included in the CORIMUNO-19 cohort
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
- 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.
- 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.
Sites / Locations
- Saint LouisRecruiting
- Réanimation médicaleRecruiting
- saint LouisRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Eculizumab
Standard of Care
Arm Description
Eculizumab
Best standard of care
Outcomes
Primary Outcome Measures
Survival without needs of intubation at day 14
Survival without needs of intubation, events considered are intubation or death
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
Secondary Outcome Measures
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
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
Survival at 14, 28 and 90 days
Overall survival
Time to discharge
Time between inclusion and hospital discharge
Time to oxygen supply independency
Time between inclusion and oxygen supply independency
Time to negative viral excretion
Time between inclusion and negative viral excretion
Incidence of secondary infections
Incidence of secondary infections (acquired pneumonia)
Vasopressor-free survival
Vasopressor-free survival
Ventilator-free survival
Ventilator-free survival
28-day ventilator-free days
Number of ventilator-free days alive up to day 28
Incidence of dialysis
Incidence of dialysis (renal replacement therapy)
PaO2/FiO2 ratio
PaO2/FiO2 ratio
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
Time to ICU discharge
Time to ICU discharge
Full Information
NCT ID
NCT04346797
First Posted
April 6, 2020
Last Updated
April 23, 2020
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT04346797
Brief Title
CORIMUNO19-ECU: Trial Evaluating Efficacy and Safety of Eculizumab (Soliris) in Patients With COVID-19 Infection, Nested in the CORIMUNO-19 Cohort
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Unknown status
Study Start Date
April 16, 2020 (Actual)
Primary Completion Date
September 30, 2020 (Anticipated)
Study Completion Date
December 31, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
SARS-CoV-2, COVID19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Bayesian open labelled randomized clinical trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Eculizumab
Arm Type
Experimental
Arm Description
Eculizumab
Arm Title
Standard of Care
Arm Type
No Intervention
Arm Description
Best standard of care
Intervention Type
Drug
Intervention Name(s)
Eculizumab
Intervention Description
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
Primary Outcome Measure Information:
Title
Survival without needs of intubation at day 14
Description
Survival without needs of intubation, events considered are intubation or death
Time Frame
14 days
Title
Change in organ failure at day 3
Description
Change in organ failure at day 3, defined by the relative variation in Sequential Organ Failure Assessment score
Time Frame
3 days
Secondary Outcome Measure Information:
Title
Intubation free survival at day 14
Description
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
Time Frame
Day 14
Title
WHO progression scale at days 4, 7 and 14
Description
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
Time Frame
4, 7 and 14 days
Title
Survival at 14, 28 and 90 days
Description
Overall survival
Time Frame
14, 28 and 90 days
Title
Time to discharge
Description
Time between inclusion and hospital discharge
Time Frame
90 days
Title
Time to oxygen supply independency
Description
Time between inclusion and oxygen supply independency
Time Frame
90 days
Title
Time to negative viral excretion
Description
Time between inclusion and negative viral excretion
Time Frame
90 days
Title
Incidence of secondary infections
Description
Incidence of secondary infections (acquired pneumonia)
Time Frame
90 days
Title
Vasopressor-free survival
Description
Vasopressor-free survival
Time Frame
90 days
Title
Ventilator-free survival
Description
Ventilator-free survival
Time Frame
90 days
Title
28-day ventilator-free days
Description
Number of ventilator-free days alive up to day 28
Time Frame
28 days
Title
Incidence of dialysis
Description
Incidence of dialysis (renal replacement therapy)
Time Frame
90 days
Title
PaO2/FiO2 ratio
Description
PaO2/FiO2 ratio
Time Frame
days 4, 7, 14
Title
Rate of respiratory acidosis at day 4
Description
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
Time Frame
4 days
Title
Time to ICU discharge
Description
Time to ICU discharge
Time Frame
90 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients between 18 and 675 years old included in the CORIMUNO-19 cohort
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
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.
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Régis Peffault de Latour, MD PhD
Phone
1 42 49 96 39
Ext
+33
Email
regis.peffaultdelatour@aphp.fr
Facility Information:
Facility Name
Saint Louis
City
Paris
State/Province
Ile De France
ZIP/Postal Code
75010
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne Bergeron-Lafaurie, MD PhD
Phone
+33 1 42 49 41 66
Email
anne.bergeron-lafaurie@aphp.fr
First Name & Middle Initial & Last Name & Degree
Anne bergeron-Lafaurie, MD PhD
Facility Name
Réanimation médicale
City
Paris
ZIP/Postal Code
75010
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elie Azoulay, MD PhD
Facility Name
saint Louis
City
Paris
ZIP/Postal Code
75010
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
R Peffault de la Tour, MD
Phone
33(1)42494949
First Name & Middle Initial & Last Name & Degree
Regis Peffault de la Tour, MD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
CORIMUNO19-ECU: Trial Evaluating Efficacy and Safety of Eculizumab (Soliris) in Patients With COVID-19 Infection, Nested in the CORIMUNO-19 Cohort
We'll reach out to this number within 24 hrs