Data show no significant difference in survival rates in the canukinumab group (88.8%) compared to placebo (85.7%).
The phrase 3 CAN-COVID trial evaluated the efficacy of an anti–interleukin-1β antibody canakinumab in patients hospitalized with severe COVID-19.
Investigators, led by Roberto Caricchio, MD, Division of Rheumatology, Lewis Katz School of Medicine, Temple University, found treatment with canakinumab did not result in a significant increase in the likelihood of survival without invasive mechanical ventilation (IMV) at day 29 of the trial.
The randomized, double-blind, placebo-controlled trial was performed at 39 hospitals in Europe and the United States.
Patients were randomly assigned 1:1 to receive a single dose of canakinumab or placebo in 250 mL of 5% dextrose infused intravenously over 2 hours.
Dosage included 450 mg for a body weight of 40 - <60 kg, 600 mg for 60-80 kg, and 750 mg for >80 kg.
Eligible patients include hospitalized patients with severe COVID-19, who were ≥12 years old in the United States and ≥18 years old in Europe with hypoxemia, but did not require IMV.
Inclusion criteria was diagnosis of infection with SARS-CoV-2 within 7 days prior to randomization, pneumonia diagnosis, peripheral capillary oxygen saturation of ≤93%, and blood levels of CRP of 20 mg/L or greater.
Exclusions included treatment with therapy targeting IL-1 or IL-6, suspected untreated active infection due to pathogens, or if progression to death was imminent within 24 hours.
Investigators noted efficacy and monitoring of adverse events (AEs) were performed daily, with laboratory assessments taking place every other day until day 29. Further, on days 57 and 127, laboratory assessments took place in hospitalized patients.
The primary outcome included the proportion of patients who survived without ever requiring IMB from day 3 to day 29.
Other outcomes included COVID-19 related mortality, measurements of biomarkers of systemic hyperinflammation, and safety evaluations.
A total of 454 adult patients hospitalized with severe COVID-19 were randomized, with a mean age of 59 years and 41.2% (n = 187) women. They noted approximately half the patients were considered obese (BMI >30).
After 6 patients withdrew from the trial, a total of 448 patients received canakinumab (n = 225) or placebo (n = 223).
Investigators noted 91.9% (n = 417) completed day 29 of the trial.
At day 29, a total of 12 patients treated with canakinumab died, while 1 discontinued the study and 1 patient did not participate in the follow-up. In addition, 16 patients who received placebo died, while 1 did not participate in the follow-up.
Following the primary outcomes, data show 198 of 223 (88.8%) of patients in the canakinumab group survived without requiring IMV between days 3 and 29.
Further, 191 of 223 (85.7%) patients survived in the placebo group, at a rate difference of 3.1% (95% CI, -3.1% - 9.3%). The team noted an odds ratio of 1.39 (95% CI, 0.76 - 2.54, P = .29). .
Secondary outcomes showed the proportion of patients with COVID-19-related mortality by day 29 included 11 of 223 (4.9%) in the canakinumab group, compared to 16 of 222 (7.2%) patients in the placebo group.
A rate difference of -2.3% (95% CI, -6.7% - 2.2%) and odds ratio of 0.67 (95% CI, 0.30 - 1.50) was noted.
Data show serious adverse events (AEs) were observed in 36 of 225 patients (16%) treated with canakinumab, compared to 46 of 223 (20.6%) patients who were given placebo.
Investigators concluded that canakinumab did not significantly increase survival rates without IMV in COVID-19 patients, compared to placebo.
“Among patients hospitalized with severe COVID-19, treatment with canakinumab, compared with placebo, did not significantly increase the likelihood of survival without IMV at day 29,” investigators wrote.
The study, “Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19: A Randomized Clinical Trial,” was published online in JAMA.