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

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

Tracking Information

• First Submitted Date: August 11, 2020
• First Posted Date: August 12, 2020
• Last Update Posted Date: September 8, 2021
• Actual Study Start Date: October 23, 2020
• Actual Primary Completion Date: August 17, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 12, 2020)

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.

Original Primary Outcome Measures (submitted: August 11, 2020)

unmatched win ratio after treatment with canakinumab compared to placebo [ Time Frame: within 4 weeks after treatment with canakinumab or placebo ]

unmatched win ratio determined by the ordered components:

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

Current Secondary Outcome Measures (submitted: August 11, 2020)

• 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"
• Death rate [ Time Frame: 4 weeks ]
  Death rate during the 4-week period after study treatment
• 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
• 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)
• Prolonged hospital stay [ Time Frame: >3 weeks ]
  Prolonged hospital stay > 3 weeks
• Change in ratio to baseline in the glycated hemoglobin [ Time Frame: Baseline, Day 29 and Day 90 ]
  Ratio to baseline in the glycated hemoglobin
• Change in ratio to baseline in the fasting glucose [ Time Frame: Baseline, Day 29 ]
  Ratio to baseline in the fasting glucose
• Change in ratio to baseline in the fasting insulin [ Time Frame: Baseline, Day 29 ]
  Ratio to baseline in the fasting insulin
• Change in ratio to baseline in the fasting c-peptide [ Time Frame: Baseline, Day 29 ]
  Ratio to baseline in the fasting c-peptide
• 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)
• Change in ratio to baseline in the D-dimer [ Time Frame: Baseline, Day 29 ]
  Ratio to baseline in the D-dimer
• 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)
• 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)
• Type of antidiabetic treatment at Day 29 [ Time Frame: Day 29 ]
  Type of antidiabetic treatment at Day 29
• Number of antidiabetic treatment at Day 29 [ Time Frame: Day 29 ]
  Number of antidiabetic treatment at Day 29
• Type of antidiabetic treatment at three months [ Time Frame: Month 3 ]
  Type of antidiabetic treatment at three months
• Number of antidiabetic treatment at three months [ Time Frame: Month 3 ]
  Number of antidiabetic treatment at three months

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Canakinumab in Patients With COVID-19 and Type 2 Diabetes
• Official Title: Canakinumab in Patients With COVID-19 and Type 2 Diabetes - CanCovDia Trial
• 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).
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Coronavirus Infection
• Diabetes Mellitus, Type 2

Intervention

• Drug: Canakinumab
  Body weight adjusted dose in 250 ml 5% dextrose solution i.v. over 2 hours
  Other Name: Ilaris®
• 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

Study Arms

• Active Comparator: active treatment arm
  Treatment with Canakinumab i.v. administered over 2 hours
  Intervention: Drug: Canakinumab
• Placebo Comparator: placebo treatment arm
  placebo treatment
  Intervention: Drug: Placebo

• Publications *: Hepprich M, Mudry JM, Gregoriano C, Jornayvaz FR, Carballo S, Wojtusciszyn A, Bart PA, Chiche JD, Fischli S, Baumgartner T, Cavelti-Weder C, Braun DL, Gunthard HF, Beuschlein F, Conen A, West E, Isenring E, Zechmann S, Bucklar G, Aubry Y, Dey L, Muller B, Hunziker P, Schutz P, Cattaneo M, Donath MY. Canakinumab in patients with COVID-19 and type 2 diabetes - A multicentre, randomised, double-blind, placebo-controlled trial. EClinicalMedicine. 2022 Sep 17;53:101649. doi: 10.1016/j.eclinm.2022.101649. eCollection 2022 Nov.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 17, 2020): 116
• Original Estimated Enrollment (submitted: August 11, 2020): 112
• Actual Study Completion Date: August 17, 2021
• Actual Primary Completion Date: August 17, 2021 (Final data collection date for primary outcome measure)

Eligibility 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-

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT04510493
• Other Study ID Numbers: 2020-02008; me20Donath2
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University Hospital, Basel, Switzerland
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospital, Basel, Switzerland
• Original Study Sponsor: Same as current

Collaborators

• Novartis
• Swiss National Science Foundation

Investigators

• Principal Investigator: Marc Donath, MD, Prof.; University Hospital Basel, Department of Endocrinology, Diabetes and Metabolism

• PRS Account: University Hospital, Basel, Switzerland
• Verification Date: September 2021