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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
454
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.
250 mL of 5% dextrose infused IV over 2 hours. Single dose on Day 1.
Participants Who Survived Without Requiring Invasive Mechanical Ventilation From Day 3 to Day 29, Primary Analysis
Number of responders who survived without requiring invasive mechanical ventilation from Day 3 to Day 29. An early dropout without requiring invasive mechanical ventilation is considered as a responder if discharged from hospital with 9-point ordinal scale\<=1 or with last 9-point ordinal scale on/after Day 15 better than baseline.
Time frame: Day 3 to Day 29
COVID-19-related Death After Study Treatment
Participants with COVID-19 related (as assessed by investigator) death up to Day 29
Time frame: 29 days
Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP)
Measurement of C Reactive Protein (mg/L), Serum Or Plasma over time. The level of C-reactive protein (CRP), which can be measured in the blood, increases when there's inflammation in the body. Lower values of ratio to baseline in the CRP indicates less inflammation. The ratio to baseline at each time point (day) for each patient is calculated as the level of a specific biomarker at the time point divided by the baseline level of the biomarker, where baseline is the last non-missing value before study treatment. The geometric mean of ratio to baseline at each time point for each treatment group is calculated by first averaging the logarithms of the ratios to baseline and then take the exponential function of the same base.
Time frame: Over time and up to day 29: Baseline, Day 2, Day 3, Day 5, Day 7, Day 9, Day 11, Day 13, Day 15, Day 17, Day 19, Day 21, Day 23, Day 25, Day 27 and Day 29.
Geometric Mean Ratio to Baseline in the D-dimer
Clinical chemistry measurement D-Dimer (mg/L FEU), Blood in a blood sample over time D-dimer is one of the protein fragments produced when a blood clot gets dissolved in the body. The ratio to baseline at each time point (day) for each patient is calculated as the level of a specific biomarker at the time point divided by the baseline level of the biomarker, where baseline is the last non-missing value before study treatment. The geometric mean of ratio to baseline at each time point for each treatment group is calculated by first averaging the logarithms of the ratios to baseline and then take the exponential function of the same base.
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Novartis Investigative Site
Birmingham, Alabama, United States
Novartis Investigative Site
Glendale, California, United States
Novartis Investigative Site
San Francisco, California, United States
Novartis Investigative Site
San Francisco, California, United States
Novartis Investigative Site
Chicago, Illinois, United States
Novartis Investigative Site
Baltimore, Maryland, United States
Novartis Investigative Site
Boston, Massachusetts, United States
Novartis Investigative Site
Boston, Massachusetts, United States
Novartis Investigative Site
Brooklyn, New York, United States
Novartis Investigative Site
Chapel Hill, North Carolina, United States
...and 29 more locations
Time frame: Over time and up to day 29: Baseline, Day 2, Day 3, Day 5, Day 7, Day 9, Day 11, Day 13, Day 15, Day 17, Day 19, Day 21, Day 23, Day 25, Day 27 and Day 29.
Geometric Mean Ratio to Baseline in Ferritin
Clinical chemistry measurement for amount of ferritin (ug/L) in Serum. The ratio to baseline at each time point (day) for each patient is calculated as the level of a specific biomarker at the time point divided by the baseline level of the biomarker, where baseline is the last non-missing value before study treatment. The geometric mean of ratio to baseline at each time point for each treatment group is calculated by first averaging the logarithms of the ratios to baseline and then take the exponential function of the same base.
Time frame: Over time and up to day 29: Baseline, Day 2, Day 3, Day 5, Day 7, Day 9, Day 11, Day 13, Day 15, Day 17, Day 19, Day 21, Day 23, Day 25, Day 27 and Day 29.
Number of Participants With Treatment Emergent Adverse Events
Number of participants with treatment emergent adverse events, including changes from baseline in vital signs and laboratory results qualifying and reported as adverse events. Safety was monitored from the canakinumab or placebo dose (Day 1) up to 126 days post-dose (Day 127).
Time frame: Up to day 127