Zilucoplan® in Improving Oxygenation and Short- and Long-term Outcome of COVID-19 Patients With Acute Hypoxic Respiratory Failure

• Status: Completed
• Trial end date: 2021-04-09
• Target enrollment: 0
• Participant gender: All

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 subcutaneously once daily for 14 days or till discharge from the hospital, whichever comes first.

The hypothesis of the proposed intervention is that Zilucoplan® (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post COVID-19, and can promote lung repair mechanisms, that lead to a 25% improvement in lung oxygenation parameters. This hypothesis is based on experiments performed in mice showing that C5a blockade can prevent mortality and prevent ARDS in mice with post-viral acute lung injury.

Eligible patients include patients with confirmed COVID-19 infection suffering from hypoxic respiratory failure defined as O2 saturation below 93% on minimal 2l/min O2 therapy and/or ratio PaO2/FiO2 below 350.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Ghent
• Collaborator: UCB Pharma

Criteria

Inclusion Criteria:

• 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 Criteria:

• 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)