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

Study Description

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.

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

• 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-

Contacts and Locations

Locations

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

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University Hospital, Basel, Switzerland
• ClinicalTrials.gov Identifier: NCT04510493
• Other Study ID Numbers: 2020-02008; me20Donath2
• First Posted: August 12, 2020
• Last Update Posted: September 8, 2021
• Last Verified: September 2021

• 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:

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