Status:
COMPLETED
Zilucoplan® in Improving Oxygenation, Short-, Longterm Outcome of COVID19 Patients With Acute Hypoxic Respiratory Failure
Lead Sponsor:
University Hospital, Ghent
Collaborating Sponsors:
UCB Pharma
Conditions:
COVID-19
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
The study is a randomized controlled, open-label trial comparing subcutaneous Zilucoplan® with standard of care to standard of care alone. In the active group, Zilucoplan® will be administered subcut...
Detailed Description
This investigator-initiated trial is a phase 2 academic, prospective, 2:1 randomized, open-label, multicenter interventional study designed to investigate the efficacy of subcutaneous Zilucoplan® in i...
Eligibility Criteria
Inclusion
- 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 :
- O2 saturation below 93% on minimal 2l/min O2 therapy; and/or
- PaO2/FiO2 below 350 mmHg (Strongly recommended: patient in upright position, after minimal 3 minutes without supplemental oxygen; In ventilated patients or ECMO 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 randomisation
- 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.
- Willing and able to provide informed consent or legal representative willing to provide informed consent
Exclusion
- 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 COVID19 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)
Key Trial Info
Start Date :
May 22 2020
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
April 9 2021
Estimated Enrollment :
81 Patients enrolled
Trial Details
Trial ID
NCT04382755
Start Date
May 22 2020
End Date
April 9 2021
Last Update
September 14 2023
Active Locations (9)
Enter a location and click search to find clinical trials sorted by distance.
1
OLVZ Aalst
Aalst, Belgium, 9300
2
AZ Sint Jan Brugge
Bruges, Belgium, 8000
3
Erasmus University Hospital
Brussels, Belgium, 1070
4
AZ Sint-Lucas
Ghent, Belgium, 9000