study of efficacy and safety of canakinumab treatment for crs in participants with covid-19-induced pneumonia

Conditions: Cytokine Release Syndrome (CRS) in Patients With COVID-19-induced Pneumonia

Summary: this was a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of canakinumab plus standard-of-care (soc) compared with placebo plus soc in patients with covid-19-induced pneumonia and cytokine release syndrome (crs).

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-\ 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.

Eligibility criteria:
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

Keywords: covid-19 cytokine release syndrome sars-cov-2 canakinumab covid coronavirus can-covid pneumonia crs