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Study of Efficacy and Safety of Canakinumab Treatment for CRS in Participants With COVID-19-induced Pneumonia (CAN-COVID)

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ClinicalTrials.gov Identifier: NCT04362813
Recruitment Status : Completed
First Posted : April 27, 2020
Results First Posted : August 16, 2021
Last Update Posted : August 16, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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).

Condition or disease Intervention/treatment Phase
Cytokine Release Syndrome (CRS) in Patients With COVID-19-induced Pneumonia Drug: Canakinumab Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 454 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Canakinumab on Cytokine Release Syndrome in Patients With COVID-19-induced Pneumonia (CAN-COVID)
Actual Study Start Date : April 30, 2020
Actual Primary Completion Date : September 16, 2020
Actual Study Completion Date : December 22, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia
Drug Information available for: Canakinumab

Arm Intervention/treatment
Experimental: 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.
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

Placebo Comparator: Placebo
250 mL of 5% dextrose infused IV over 2 hours. Single dose on Day 1.
Drug: Placebo
250 mL of 5% dextrose infused IV over 2 hours. Single dose on Day 1.




Primary Outcome Measures :
  1. Participants Who Survived Without Requiring Invasive Mechanical Ventilation From Day 3 to Day 29, Primary Analysis [ Time Frame: 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 Outcome Measures :
  1. COVID-19-related Death After Study Treatment [ Time Frame: 29 days ]
    Participants with COVID-19 related (as assessed by investigator) death up to Day 29

  2. Geometric Mean Ratio to Baseline in the C-reactive Protein (CRP) [ 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. ]
    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.

  3. Geometric Mean Ratio to Baseline in the D-dimer [ 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. ]

    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.


  4. Geometric Mean Ratio to Baseline in Ferritin [ 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. ]
    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.

  5. Number of Participants With Treatment Emergent Adverse Events [ Time Frame: 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).




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04362813


Locations
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United States, Alabama
Novartis Investigative Site
Birmingham, Alabama, United States, 35294
United States, California
Novartis Investigative Site
Glendale, California, United States, 91206
Novartis Investigative Site
San Francisco, California, United States, 94110
Novartis Investigative Site
San Francisco, California, United States, 94143
United States, Illinois
Novartis Investigative Site
Chicago, Illinois, United States, 60611
United States, Maryland
Novartis Investigative Site
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Novartis Investigative Site
Boston, Massachusetts, United States, 02115
Novartis Investigative Site
Boston, Massachusetts, United States, 02118
United States, New York
Novartis Investigative Site
Brooklyn, New York, United States, 11219
United States, North Carolina
Novartis Investigative Site
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Novartis Investigative Site
Cleveland, Ohio, United States, 44106-5000
United States, Pennsylvania
Novartis Investigative Site
Philadelphia, Pennsylvania, United States, 19140
United States, Texas
Novartis Investigative Site
Houston, Texas, United States, 77030
United States, Virginia
Novartis Investigative Site
Richmond, Virginia, United States, 23298
United States, Washington
Novartis Investigative Site
Tacoma, Washington, United States, 98405
France
Novartis Investigative Site
Toulouse Cedex 4, France, 31054
Italy
Novartis Investigative Site
Bergamo, BG, Italy, 24127
Novartis Investigative Site
Cona, FE, Italy, 44100
Russian Federation
Novartis Investigative Site
Barnaul, Russian Federation, 656045
Novartis Investigative Site
Moscow, Russian Federation, 111539
Novartis Investigative Site
Moscow, Russian Federation, 121309
Novartis Investigative Site
Moscow, Russian Federation, 123056
Novartis Investigative Site
Moscow, Russian Federation, 123182
Novartis Investigative Site
Ryazan, Russian Federation, 390039
Novartis Investigative Site
S-Petersburg, Russian Federation, 194354
Novartis Investigative Site
Saint Petersburg, Russian Federation, 197022
Novartis Investigative Site
Sestroretsk, Russian Federation, 197706
Novartis Investigative Site
St Petersburg, Russian Federation, 193312
Spain
Novartis Investigative Site
Hospitalet de Llobregat, Barcelona, Spain, 08907
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
San Sebastian de los Reyes, Madrid, Spain, 28702
Novartis Investigative Site
Madrid, Spain, 28034
Novartis Investigative Site
Madrid, Spain, 28040
Novartis Investigative Site
Madrid, Spain, 28041
United Kingdom
Novartis Investigative Site
Barnet, United Kingdom, EN5 3DJ
Novartis Investigative Site
Coventry, United Kingdom, CV2 2DX
Novartis Investigative Site
Leeds, United Kingdom, LS9 7TF
Novartis Investigative Site
London, United Kingdom, NW3 2QG
Novartis Investigative Site
London, United Kingdom, SE5 9RS
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartiis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] June 1, 2020
Statistical Analysis Plan  [PDF] February 15, 2021

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04362813    
Other Study ID Numbers: CACZ885D2310
2020-001370-30 ( EudraCT Number )
First Posted: April 27, 2020    Key Record Dates
Results First Posted: August 16, 2021
Last Update Posted: August 16, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
COVID-19
cytokine release syndrome
SARS-CoV-2
canakinumab
COVID
coronavirus
CAN-COVID
pneumonia
CRS
Additional relevant MeSH terms:
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COVID-19
Pneumonia
Syndrome
Cytokine Release Syndrome
Disease
Pathologic Processes
Respiratory Tract Infections
Infections
Pneumonia, Viral
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Systemic Inflammatory Response Syndrome
Inflammation
Shock