Intervention: Zilucoplan
Trial phase: Phase 2
ATC code: L04AJ06
SMILES: CCCCCCCCCCCCCCCC(=O)N[C@@H](CCC(=O)NCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)NCCCC[C@H](NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1c[nH]c2ncccc12)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)N(C)C(=O)[C@@H]1CC(=O)NCCCC[C@H](NC(C)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccccc2)C(=O)N1)C(C)(C)C)C1CCCCC1)C(=O)O)C(=O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 54
Group description: Standard of Care (SoC) + subcutaneous Zilucoplan® + prophylactic antibiotics until 14 days after last Zilucoplan®

Zilucoplan®: 14 days of SC Zilucoplan® on top of standard of care + prophylactic antibiotics until 14 days after last Zilucoplan®
Eligibility 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)