Cytokine Release Syndrome (CRS) in Patients With COVID-19-induced Pneumonia
Conditions
Keywords
COVID-19, cytokine release syndrome, SARS-CoV-2, canakinumab, COVID, coronavirus, CAN-COVID, pneumonia, CRS
Brief 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).
Detailed description
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.
Interventions
DRUGCanakinumab
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.
DRUGPlacebo
250 mL of 5% dextrose infused IV over 2 hours. Single dose on Day 1.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants Who Survived Without Requiring Invasive Mechanical Ventilation From Day 3 to Day 29, Primary Analysis | Day 3 to Day 29 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| COVID-19-related Death After Study Treatment | 29 days | Participants with COVID-19 related (as assessed by investigator) death up to Day 29 |
| Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | 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. | 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. |
| Geometric Mean Ratio to Baseline in the D-dimer | 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. | 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. |
| Geometric Mean Ratio to Baseline in Ferritin | 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. | 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. |
| Number of Participants With Treatment Emergent Adverse Events | Up to day 127 | 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). |
Countries
France, Italy, Russia, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants took part at 39 investigative sites in 6 countries. While patient flow shows 454 participants enrolled, only 451 randomized. 3 were mis-randomized i.e. assigned a randomization number in error and not treated.
Pre-assignment details
Participants were screened within 24 hours prior to enrollment.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 227 |
| Placebo 250 mL of 5% dextrose infused IV over 2 hours. Single dose on Day 1. | 227 |
| Total | 454 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 12 | 16 |
| Overall Study | Enrolled but did not receive treatment | 2 | 4 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 3 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Canakinumab | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 58.5 years STANDARD_DEVIATION 14.55 | 57.8 years STANDARD_DEVIATION 13.89 | 58.2 years STANDARD_DEVIATION 14.21 |
| Age, Customized < 18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=65 years | 78 Participants | 72 Participants | 150 Participants |
| Age, Customized Between 18 and 64 years | 149 Participants | 155 Participants | 304 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 8 Participants | 11 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 9 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 35 Participants | 37 Participants | 72 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 5 Participants | 6 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 19 Participants | 12 Participants | 31 Participants |
| Race (NIH/OMB) White | 159 Participants | 156 Participants | 315 Participants |
| Sex: Female, Male Female | 92 Participants | 95 Participants | 187 Participants |
| Sex: Female, Male Male | 135 Participants | 132 Participants | 267 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 22 / 225 | 26 / 223 |
| other Total, other adverse events | 15 / 225 | 19 / 223 |
| serious Total, serious adverse events | 47 / 225 | 53 / 223 |
Outcome results
Primary
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
Population: Randomized participants with at least one assessment of the 9-point ordinal scale between Day 3 and Day 29 (where value 0 = uninfected, and 8 = death)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Canakinumab | Participants Who Survived Without Requiring Invasive Mechanical Ventilation From Day 3 to Day 29, Primary Analysis | 198 Participants |
| Placebo | Participants Who Survived Without Requiring Invasive Mechanical Ventilation From Day 3 to Day 29, Primary Analysis | 191 Participants |
Comparison: Odds ratio is based on a Logistic regression model adjusted by treatment, region (North America vs Europe), and baseline 9-point ordinal scale (\<=4, \>=5).p-value: 0.287495% CI: [0.76, 2.54]Regression, Logistic
Secondary
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
Population: All randomized participants including those who did not receive any dose, as per intent-to-treat principle, and excluding early dropouts if the last available 9-point ordinal scale \>1 (including non-COVID-19 related death)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Canakinumab | COVID-19-related Death After Study Treatment | 11 Participants |
| Placebo | COVID-19-related Death After Study Treatment | 16 Participants |
Comparison: Odds ratio is based on a Logistic regression model adjusted by treatment, region (North America vs Europe), and baseline 9-point ordinal scale (\<=4, \>=5)p-value: 0.330395% CI: [0.3, 1.5]Regression, Logistic
Secondary
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.
Population: Randomized participants with a valid assessment for the outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Canakinumab | Geometric Mean Ratio to Baseline in Ferritin | Day 21 | 0.514 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in Ferritin | Day 29 | 0.543 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in Ferritin | Day 11 | 0.618 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in Ferritin | Day 2 | 0.996 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in Ferritin | Day 23 | 0.469 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in Ferritin | Day 3 | 0.921 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in Ferritin | Day 19 | 0.545 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in Ferritin | Day 5 | 0.825 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in Ferritin | Day 25 | 0.542 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in Ferritin | Day 7 | 0.761 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in Ferritin | Day 9 | 0.676 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in Ferritin | Day 17 | 0.534 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in Ferritin | Day 13 | 0.582 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in Ferritin | Day 27 | 0.490 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in Ferritin | Day 15 | 0.535 ratio |
| Placebo | Geometric Mean Ratio to Baseline in Ferritin | Day 27 | 0.809 ratio |
| Placebo | Geometric Mean Ratio to Baseline in Ferritin | Day 19 | 0.644 ratio |
| Placebo | Geometric Mean Ratio to Baseline in Ferritin | Day 15 | 0.618 ratio |
| Placebo | Geometric Mean Ratio to Baseline in Ferritin | Day 17 | 0.641 ratio |
| Placebo | Geometric Mean Ratio to Baseline in Ferritin | Day 29 | 0.517 ratio |
| Placebo | Geometric Mean Ratio to Baseline in Ferritin | Day 21 | 0.644 ratio |
| Placebo | Geometric Mean Ratio to Baseline in Ferritin | Day 23 | 0.692 ratio |
| Placebo | Geometric Mean Ratio to Baseline in Ferritin | Day 25 | 0.745 ratio |
| Placebo | Geometric Mean Ratio to Baseline in Ferritin | Day 7 | 0.815 ratio |
| Placebo | Geometric Mean Ratio to Baseline in Ferritin | Day 9 | 0.764 ratio |
| Placebo | Geometric Mean Ratio to Baseline in Ferritin | Day 2 | 1.014 ratio |
| Placebo | Geometric Mean Ratio to Baseline in Ferritin | Day 3 | 1.014 ratio |
| Placebo | Geometric Mean Ratio to Baseline in Ferritin | Day 5 | 0.879 ratio |
| Placebo | Geometric Mean Ratio to Baseline in Ferritin | Day 11 | 0.735 ratio |
| Placebo | Geometric Mean Ratio to Baseline in Ferritin | Day 13 | 0.684 ratio |
Secondary
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.
Population: Randomized participants with a valid assessment for the outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Canakinumab | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 7 | 0.160 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 15 | 0.133 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 17 | 0.123 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 2 | 0.726 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 19 | 0.123 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 9 | 0.131 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 21 | 0.115 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 5 | 0.255 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 23 | 0.106 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 11 | 0.099 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 25 | 0.126 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 3 | 0.479 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 27 | 0.175 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 29 | 0.240 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 13 | 0.108 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 29 | 0.258 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 27 | 0.331 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 2 | 0.785 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 3 | 0.649 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 5 | 0.384 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 7 | 0.238 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 9 | 0.159 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 11 | 0.133 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 13 | 0.141 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 17 | 0.289 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 19 | 0.368 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 21 | 0.296 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 23 | 0.400 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 25 | 0.368 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) | Day 15 | 0.149 ratio |
Secondary
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.
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.
Population: FAS
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Canakinumab | Geometric Mean Ratio to Baseline in the D-dimer | Day 3 | 0.992 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the D-dimer | Day 17 | 1.033 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the D-dimer | Day 9 | 1.164 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the D-dimer | Day 19 | 1.520 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the D-dimer | Day 2 | 1.032 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the D-dimer | Day 21 | 1.431 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the D-dimer | Day 11 | 1.162 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the D-dimer | Day 23 | 1.208 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the D-dimer | Day 5 | 1.094 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the D-dimer | Day 25 | 2.670 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the D-dimer | Day 13 | 1.135 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the D-dimer | Day 27 | 1.785 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the D-dimer | Day 7 | 1.038 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the D-dimer | Day 29 | 1.818 ratio |
| Canakinumab | Geometric Mean Ratio to Baseline in the D-dimer | Day 15 | 1.100 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the D-dimer | Day 29 | 2.441 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the D-dimer | Day 2 | 1.028 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the D-dimer | Day 3 | 1.188 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the D-dimer | Day 7 | 1.244 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the D-dimer | Day 9 | 1.184 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the D-dimer | Day 11 | 1.115 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the D-dimer | Day 13 | 1.184 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the D-dimer | Day 15 | 1.078 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the D-dimer | Day 17 | 1.384 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the D-dimer | Day 19 | 1.446 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the D-dimer | Day 21 | 1.443 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the D-dimer | Day 23 | 1.521 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the D-dimer | Day 25 | 1.808 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the D-dimer | Day 27 | 2.262 ratio |
| Placebo | Geometric Mean Ratio to Baseline in the D-dimer | Day 5 | 1.188 ratio |
Secondary
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
Population: Safety Set comprises all participants who received at least one dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Canakinumab | Number of Participants With Treatment Emergent Adverse Events | 141 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events | 140 Participants |