Study of Efficacy and Safety of Canakinumab Treatment for CRS in Participants With COVID-19-induced Pneumonia

This was a Phase III, multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of canakinumab in patients with COVID-19-induced pneumonia and cytokine release syndrome (CRS). The study enrolled patients to canakinumab or placebo, in addition to standard of care (SOC) per local practice, which may have included anti-viral treatment, corticosteroids and/or supportive care.

Patients who met the inclusion/exclusion criteria were randomized in a 1:1 ratio to either canakinumab + SOC or placebo + SOC and were dosed immediately after ensuring that the patient met all eligibility criteria. Patients in the canakinumab arm were dosed on Day 1 with canakinumab 450 mg for body weight of 40-<60 kg, 600 mg for 60-80 kg or 750 mg for >80 kg in 250 mL of 5% dextrose infused IV over 2 hours. Patients in the placebo arm were administered with 250 mL of 5% dextrose infused IV over 2 hours.

The study included:

• Screening period of 0-1 day
• Study period from initial dose on Day 1 to Day 29 or hospital discharge
• Follow-up to Day 127 The primary objective was to demonstrate the benefit of canakinumab + SOC in increasing the chance of survival without ever requiring invasive mechanical ventilation among patients with COVID-19-induced pneumonia and CRS.

Key inclusion Criteria:

• Adults ≥ 18 years old (for US only: patients ≥ 12 years old, although no children ever enrolled. This was an adult trial.)
• Body weight ≥40 kg
• Informed consent must be obtained prior to participation in this study. For US patients 12 - < 18 years old; parent/guardian consent must be obtained and assent if applicable.
• Clinically diagnosed with SARS-CoV-2 virus by PCR or by other approved diagnostic methodology
• Hospitalized with COVID-19-induced pneumonia evidenced by chest x-ray or CT scan with pulmonary infiltrates
• SpO2 ≤ 93% on room air or arterial oxygen partial pressure (PaO2)/ fraction of inspired oxygen (FiO2) < 300mmHg
• C-reactive protein ≥20 mg/L or ferritin level ≥600 µg/L

Key exclusion Criteria:

• History of hypersensitivity to canakinumab or to biologic drugs
• Intubated and on mechanical ventilation (invasive) at time of randomization
• Treatment with immunomodulators or immunosuppressant drugs, including but not limited to tocilizumab, TNF inhibitors and anti-IL-17 agents within 5 half-lives or 30 days (whichever is longer) prior to randomization with the exception of anakinra which is excluded within 5 half-lives only. Note: Immunomodulators (topical or inhaled) for asthma and atopic dermatitis and corticosteroids (any route of administration) are permitted.
• Suspected or known untreated active bacterial, fungal, viral, or parasitic infection with the exception of COVID-19