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Canakinumab in Patients With COVID-19 and Type 2 Diabetes (CanCovDia)

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ClinicalTrials.gov Identifier: NCT04510493
Recruitment Status : Completed
First Posted : August 12, 2020
Last Update Posted : September 8, 2021
Sponsor:
Collaborators:
Novartis
Swiss National Science Foundation
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Brief Summary:
The purpose of this study is to evaluate whether Canakinumab has beneficial effects on patients with Type 2 diabetes mellitus and coronavirus disease 19 (COVID19).

Condition or disease Intervention/treatment Phase
Coronavirus Infection Diabetes Mellitus, Type 2 Drug: Canakinumab Drug: Placebo Phase 3

Detailed Description:
Patients with a metabolic syndrome (overweight, diabetes, hypertension) have a particularly bad outcome if infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). This may be explained by an over-activation of the Interleukin-1 (IL-1) beta system. Metabolic stress (increased glucose and lipid levels) induces NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) -mediated IL-1beta secretion. SARS-CoV2 also activates NLRP3. Therefore, the study proposes that metabolic stress in patients with overweight and diabetes potentiates COVID-19 induced hyperinflammatory syndrome leading to excess mortality in these vulnerable patients. Canakinumab (Ilaris®) is a recombinant, human monoclonal antibody antagonizing IL-1beta by blocking IL-1beta activity. The aim of the study is to investigate the effect of canakinumab in type 2 diabetic patients with COVID-19.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 116 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Canakinumab in Patients With COVID-19 and Type 2 Diabetes - CanCovDia Trial
Actual Study Start Date : October 23, 2020
Actual Primary Completion Date : August 17, 2021
Actual Study Completion Date : August 17, 2021


Arm Intervention/treatment
Active Comparator: active treatment arm
Treatment with Canakinumab i.v. administered over 2 hours
Drug: Canakinumab
Body weight adjusted dose in 250 ml 5% dextrose solution i.v. over 2 hours
Other Name: Ilaris®

Placebo Comparator: placebo treatment arm
placebo treatment
Drug: Placebo
Aqua ad injectabilia in 250 ml 5% dextrose solution i.v. over 2 hours
Other Name: Aqua ad injectabilia in 250 ml 5% dextrose solution




Primary Outcome Measures :
  1. unmatched win ratio after treatment with canakinumab compared to Placebo (composite endpoint) [ Time Frame: within 4 weeks after treatment with canakinumab or placebo ]

    Treatment and placebo will be compared on the basis of the unmatched win-ratio approach of Pocock. When comparing two patients, the winner will be determined by the first component in which the two patients differ (4 weeks after randomization):

    1. longer survival time
    2. longer ventilation-free time
    3. longer ICU-free time
    4. shorter hospitalization time

    If there is no difference between treatment and Placebo: the win ratio is 1. If there is a difference between treatment and Placebo: the win ratio is not 1.



Secondary Outcome Measures :
  1. Time to clinical improvement [ Time Frame: From randomization up to 4 weeks ]

    Time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever comes first. "The seven-category ordinal scale consists of the following categories:

    1. not hospitalized with resumption of normal activities;
    2. not hospitalized, but unable to resume normal activities;
    3. hospitalized, not requiring supplemental oxygen;
    4. hospitalized, requiring supplemental oxygen;
    5. hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both;
    6. hospitalized, requiring extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, or both; and
    7. death"

  2. Death rate [ Time Frame: 4 weeks ]
    Death rate during the 4-week period after study treatment

  3. Admission to intensive care unit (ICU) [ Time Frame: 4 weeks ]
    Admission to the intensive care unit from the medical ward during the 4-week period after study treatment

  4. Secondary worsening of disease [ Time Frame: 4 weeks ]
    Secondary worsening of disease (i.e., development of Acute respiratory distress Syndrome (ARDS), increase of oxygen demand after 72h of treatment)

  5. Prolonged hospital stay [ Time Frame: >3 weeks ]
    Prolonged hospital stay > 3 weeks

  6. Change in ratio to baseline in the glycated hemoglobin [ Time Frame: Baseline, Day 29 and Day 90 ]
    Ratio to baseline in the glycated hemoglobin

  7. Change in ratio to baseline in the fasting glucose [ Time Frame: Baseline, Day 29 ]
    Ratio to baseline in the fasting glucose

  8. Change in ratio to baseline in the fasting insulin [ Time Frame: Baseline, Day 29 ]
    Ratio to baseline in the fasting insulin

  9. Change in ratio to baseline in the fasting c-peptide [ Time Frame: Baseline, Day 29 ]
    Ratio to baseline in the fasting c-peptide

  10. Ratio to baseline in the C-reactive protein (CRP) [ Time Frame: Baseline, Day 29 and Day 90 ]
    Ratio to baseline in the C-reactive protein (CRP)

  11. Change in ratio to baseline in the D-dimer [ Time Frame: Baseline, Day 29 ]
    Ratio to baseline in the D-dimer

  12. Change in ratio to baseline in the Natriuretic peptide (NTproBNP) [ Time Frame: Baseline, Day 29 and Day 90 ]
    Ratio to baseline in the Natriuretic peptide (NTproBNP)

  13. Change in ratio to baseline in the Glomerular Filtration Rate Renal (eGFR) [ Time Frame: Baseline, Day 29 and Day 90 ]
    Ratio to baseline in the Glomerular Filtration Rate Renal (eGFR)

  14. Type of antidiabetic treatment at Day 29 [ Time Frame: Day 29 ]
    Type of antidiabetic treatment at Day 29

  15. Number of antidiabetic treatment at Day 29 [ Time Frame: Day 29 ]
    Number of antidiabetic treatment at Day 29

  16. Type of antidiabetic treatment at three months [ Time Frame: Month 3 ]
    Type of antidiabetic treatment at three months

  17. Number of antidiabetic treatment at three months [ Time Frame: Month 3 ]
    Number of antidiabetic treatment at three months



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

Inclusion Criteria:

  • Diagnosis of type 2 diabetes mellitus
  • Body mass index > 25 kg/m² (overweight)
  • Hospitalized with COVID-19

Exclusion Criteria:

  • Suspected or known untreated active bacterial, fungal, viral, or parasitic infection with the exception of COVID-19
  • Treatment with immunomodulators or immunosuppressant drugs, including but not limited to tocilizumab, tumor necrosis factor (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) such as dexamethasone are permitted.
  • History of hypersensitivity to canakinumab or to biologic drugs
  • Neutrophil count <1000/mm3
  • Pregnant or nursing (lactating) women
  • Participation in another study with investigational drug within the 30 days preceding and during the present study-

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): NCT04510493


Locations
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Switzerland
University Medical Clinic Aarau
Aarau, Switzerland, 5001
University Hospital Basel
Basel, Switzerland, 4031
University Hospital Bern
Bern, Switzerland, 3010
Hopital du Jura
Delémont, Switzerland, 2800
University Hospital Geneva
Geneva, Switzerland, 1205
University Hospital Lausanne
Lausanne, Switzerland, 1011
Cantonal Hospital Lucerne
Luzern, Switzerland, 6004
Cantonal Hospital St Gallen
St. Gallen, Switzerland, 9001
University Hospital Zürich
Zürich, Switzerland, 8091
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Novartis
Swiss National Science Foundation
Investigators
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Principal Investigator: Marc Donath, MD, Prof. University Hospital Basel, Department of Endocrinology, Diabetes and Metabolism
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Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT04510493    
Other Study ID Numbers: 2020-02008; me20Donath2
First Posted: August 12, 2020    Key Record Dates
Last Update Posted: September 8, 2021
Last Verified: September 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Basel, Switzerland:
NLRP3
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Coronavirus Disease 19 (COVID-19)
IL-1beta
hyperinflammatory syndrome
obesity
Additional relevant MeSH terms:
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COVID-19
Coronavirus Infections
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases