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-<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.
Drug: Canakinumab
Canakinumab 450 mg for body weight 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. Single dose on Day 1.
Other Name: ACZ885
Drug: Placebo
250 mL of 5% dextrose infused IV over 2 hours. Single dose on Day 1.
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
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Toulouse Cedex 4, France
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Bergamo, BG, Italy
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Cona, FE, Italy
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Barnaul, Russian Federation
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Hospitalet de Llobregat, Barcelona, Spain
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Madrid, Spain
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Barnet, United Kingdom
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Novartis Pharmaceuticals, Study Director
Novartiis Pharmaceuticals