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

• ClinicalTrials.gov Identifier: NCT04346797
• Recruitment Status: Unknown
• First Posted: April 15, 2020
• Last Update Posted: April 27, 2020
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Tracking Information

• First Submitted Date: April 6, 2020
• First Posted Date: April 15, 2020
• Last Update Posted Date: April 27, 2020
• Actual Study Start Date: April 16, 2020
• Estimated Primary Completion Date: September 30, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 10, 2020)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 23, 2020)

• Intubation free survival at day 14 [ Time Frame: 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 [ Time Frame: 4, 7 and 14 days ]
  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 [ Time Frame: 14, 28 and 90 days ]
  Overall survival
• Time to discharge [ Time Frame: 90 days ]
  Time between inclusion and hospital discharge
• Time to oxygen supply independency [ Time Frame: 90 days ]
  Time between inclusion and oxygen supply independency
• Time to negative viral excretion [ Time Frame: 90 days ]
  Time between inclusion and negative viral excretion
• Incidence of secondary infections [ Time Frame: 90 days ]
  Incidence of secondary infections (acquired pneumonia)
• Vasopressor-free survival [ Time Frame: 90 days ]
  Vasopressor-free survival
• Ventilator-free survival [ Time Frame: 90 days ]
  Ventilator-free survival
• 28-day ventilator-free days [ Time Frame: 28 days ]
  Number of ventilator-free days alive up to day 28
• Incidence of dialysis [ Time Frame: 90 days ]
  Incidence of dialysis (renal replacement therapy)
• PaO2/FiO2 ratio [ Time Frame: days 4, 7, 14 ]
  PaO2/FiO2 ratio
• Rate of respiratory acidosis at day 4 [ Time Frame: 4 days ]
  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 Frame: 90 days ]
  Time to ICU discharge

Original Secondary Outcome Measures (submitted: April 10, 2020)

• OMS progression scale ≤5 at day 4 [ Time Frame: Day 4 ]
  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
• OMS progression scale at days 4, 7 and 14 [ Time Frame: 4, 7 and 14 days ]
  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 [ Time Frame: 14, 28 and 90 days ]
  Overall survival
• Time to discharge [ Time Frame: 90 days ]
  Time between inclusion and hospital discharge
• Time to oxygen supply independency [ Time Frame: 90 days ]
  Time between inclusion and oxygen supply independency
• Time to negative viral excretion [ Time Frame: 90 days ]
  Time between inclusion and negative viral excretion
• Incidence of secondary infections [ Time Frame: 90 days ]
  Incidence of secondary infections (acquired pneumonia)
• Vasopressor-free survival [ Time Frame: 90 days ]
  Vasopressor-free survival
• Ventilator-free survival [ Time Frame: 90 days ]
  Ventilator-free survival
• 28-day ventilator-free days [ Time Frame: 28 days ]
  Number of ventilator-free days alive up to day 28
• Incidence of dialysis [ Time Frame: 90 days ]
  Incidence of dialysis (renal replacement therapy)
• PaO2/FiO2 ratio [ Time Frame: days 4, 7, 14 ]
  PaO2/FiO2 ratio
• Rate of respiratory acidosis at day 4 [ Time Frame: 4 days ]
  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 Frame: 90 days ]
  Time to ICU discharge

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Bayesian open labelled randomized clinical trial

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• SARS-CoV-2
• COVID19

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

Study Arms

• Experimental: Eculizumab
  Eculizumab
  Intervention: Drug: Eculizumab
• No Intervention: Standard of Care
  Best standard of care

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: April 10, 2020): 120
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2020
• Estimated Primary Completion Date: September 30, 2020 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT04346797
• Other Study ID Numbers: APHP200375-4
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Assistance Publique - Hôpitaux de Paris
• Original Responsible Party: Same as current
• Current Study Sponsor: Assistance Publique - Hôpitaux de Paris
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Assistance Publique - Hôpitaux de Paris
• Verification Date: April 2020