Zilucoplan® in patients with acute hypoxic respiratory failure due to COVID-19
- Conditions
- COVID-19 patients with acute hypoxic respiratory failure.Therapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2020-002130-33-BE
- Lead Sponsor
- niversity Hospital Ghent
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 81
-Recent (=6 days and =16 days of flu-like symptoms or malaise prior to randomization) infection with COVID-19.
-COVID-19 diagnosis confirmed by antigen detection test and/or PCR and/or positive serology, or any emerging and validated diagnostic laboratory test for COVID-19 within this period. For patients with a negative SARS-CoV-2 PCR and either a positive SARS-CoV-2 antigen or antibody test, the presence of suggestive lesions for COVID-19 on chest-CT scan is mandatory.
-In some patients, it may be impossible to get a confident laboratory confirmation of COVID-19 diagnosis after 24h of hospital admission because viral load is low and/or problems with diagnostic sensitivity. In those cases, in absence of an alternative diagnosis, and with highly suspect bilateral ground glass opacities on recent (<24h) chest-CT scan (confirmed by a radiologist and pulmonary physician as probable COVID-19), and a typical clinical and chemical diagnosis with signs of cytokine release syndrome, a patient can be enrolled as probable SARS-CoV-2-infected. In all cases, this needs confirmation by later seroconversion.
-Presence of hypoxia defined as
1)O2 saturation below 93% on minimal 2l/min O2 therapy;
and/or 2) Patient on ECMO or PaO2/FiO2 below 350 mmHg (Strongly recommended: patient in upright position, after minimal 3 minutes without supplemental oxygen; In ventilated patients PaO2 can be taken from invasive arterial line and FiO2 taken directly from mechanical ventilation settings).
-Signs of acute lung injury and/or cytokine release syndrome defined as
ANY of the following
-serum ferritin concentration >1000 mcg/L and rising since last 24h
-single ferritin above 2000 mcg/L in patients requiring immediate high flow oxygen device (Optiflow) or non-invasive or invasive mechanical ventilation
-lymphopenia defined as <800 lymphocytes/microliter and two of the following extra criteria
-Ferritin > 700 mcg/L and rising since last 24h
-increased LDH (above 300 IU/L) and rising since last 24h
-D-Dimers > 1000 ng/mL and rising since last 24h
-CRP above 70 mg/L and rising since last 24h and absence of bacterial infection
-if three of the above are present at admission, no need to document 24h rise
-Low dose Chest CT or HRCT or Angio Chest CT scan showing bilateral infiltrates within last 2 days prior to randomization
-Admitted to specialized COVID-19 ward or an ICU ward taking care of COVID-19 patients
-Age = 18 years
- Women of childbearing potential must have a negative serum pregnancy test pre-dose on day 1. Women of childbearing potential must consistently and correctly use (during the entire treatment period and 4weeks after last Zilucoplan® administration ) at least 1 highly effective method for contraception.
Male subjects (who have not been surgically sterilized by vasectomy) must agree to use effective contraception during the study.
-Willing and able to provide informed consent or legal representative willing to provide informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 41
-Patients with known history of serious allergic reactions, including anaphylaxis, to Zilucoplan® or inability to receive antibiotic prophylaxis due to allergy to ALL of the antibiotics that can be given for prophylaxis of meningococcal disease
-History of active or past meningococcal disease
-Invasive mechanical ventilation > 24 h at randomization
-Patient on ECMO at screening
-Clinical frailty scale above 3 before onset of the COVID-19 episode
-Weight below 54 kg as measured max 1 week prior to inclusion
-Weight above 150 kg as measured max 1 week prior to inclusion
-Active bacterial or fungal infection
-Unlikely to survive beyond 48h
-Neutrophil count below 1500 cells/microliter
-Platelets below 50.000/microliter
-Patients enrolled in another investigational drug study
-Patients on high dose systemic steroids (> 8 mg methylprednisolone or equivalent for more than 1 month) or other moderately immunosuppressive drugs (in the opinion of the investigator) for COVID-19 unrelated disorder
-Patients on current complement inhibiting drugs
-Serum transaminase levels >5 times upper limit of normal, unless there are clear signs of cytokine release syndrome defined by LDH >300 IU/L and ferritin >700 ng/ml
-Pregnant or breastfeeding females (all female subjects deemed of childbearing potential by the investigator must have negative pregnancy test at screening)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method