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

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

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).

Study Overview

• Status: Completed
• Conditions: Coronavirus Infection; Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Canakinumab; Drug: Placebo

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
• Enrollment (Actual): 116
• Phase: Phase 3

Contacts and Locations

Study Locations

• Switzerland
  • Aarau, Switzerland, 5001
    • University Medical Clinic Aarau
  • Basel, Switzerland, 4031
    • University Hospital Basel
  • Bern, Switzerland, 3010
    • University Hospital Bern
  • Delémont, Switzerland, 2800
    • Hopital du Jura
  • Geneva, Switzerland, 1205
    • University Hospital Geneva
  • Lausanne, Switzerland, 1011
    • University Hospital Lausanne
  • Luzern, Switzerland, 6004
    • Cantonal Hospital Lucerne
  • St. Gallen, Switzerland, 9001
    • Cantonal Hospital St Gallen
  • Zürich, Switzerland, 8091
    • University Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: Aqua ad injectabilia in 250 ml 5% dextrose solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
unmatched win ratio after treatment with canakinumab compared to Placebo (composite endpoint)	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): longer survival time; longer ventilation-free time; longer ICU-free time; 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.	within 4 weeks after treatment with canakinumab or placebo

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to clinical improvement	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: not hospitalized with resumption of normal activities;; not hospitalized, but unable to resume normal activities;; hospitalized, not requiring supplemental oxygen;; hospitalized, requiring supplemental oxygen;; hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both;; hospitalized, requiring extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, or both; and; death"	From randomization up to 4 weeks
Death rate	Death rate during the 4-week period after study treatment	4 weeks
Admission to intensive care unit (ICU)	Admission to the intensive care unit from the medical ward during the 4-week period after study treatment	4 weeks
Secondary worsening of disease	Secondary worsening of disease (i.e., development of Acute respiratory distress Syndrome (ARDS), increase of oxygen demand after 72h of treatment)	4 weeks
Prolonged hospital stay	Prolonged hospital stay > 3 weeks	>3 weeks
Change in ratio to baseline in the glycated hemoglobin	Ratio to baseline in the glycated hemoglobin	Baseline, Day 29 and Day 90
Change in ratio to baseline in the fasting glucose	Ratio to baseline in the fasting glucose	Baseline, Day 29
Change in ratio to baseline in the fasting insulin	Ratio to baseline in the fasting insulin	Baseline, Day 29
Change in ratio to baseline in the fasting c-peptide	Ratio to baseline in the fasting c-peptide	Baseline, Day 29
Ratio to baseline in the C-reactive protein (CRP)	Ratio to baseline in the C-reactive protein (CRP)	Baseline, Day 29 and Day 90
Change in ratio to baseline in the D-dimer	Ratio to baseline in the D-dimer	Baseline, Day 29
Change in ratio to baseline in the Natriuretic peptide (NTproBNP)	Ratio to baseline in the Natriuretic peptide (NTproBNP)	Baseline, Day 29 and Day 90
Change in ratio to baseline in the Glomerular Filtration Rate Renal (eGFR)	Ratio to baseline in the Glomerular Filtration Rate Renal (eGFR)	Baseline, Day 29 and Day 90
Type of antidiabetic treatment at Day 29	Type of antidiabetic treatment at Day 29	Day 29
Number of antidiabetic treatment at Day 29	Number of antidiabetic treatment at Day 29	Day 29
Type of antidiabetic treatment at three months	Type of antidiabetic treatment at three months	Month 3
Number of antidiabetic treatment at three months	Number of antidiabetic treatment at three months	Month 3

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Novartis; Swiss National Science Foundation
• Investigators: Principal Investigator: Marc Donath, MD, Prof., University Hospital Basel, Department of Endocrinology, Diabetes and Metabolism

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2020
• Primary Completion (Actual): August 17, 2021
• Study Completion (Actual): August 17, 2021

Study Registration Dates

• First Submitted: August 11, 2020
• First Submitted That Met QC Criteria: August 11, 2020
• First Posted (Actual): August 12, 2020

Study Record Updates

• Last Update Posted (Actual): September 8, 2021
• Last Update Submitted That Met QC Criteria: September 7, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: obesity; NLRP3; Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); Coronavirus Disease 19 (COVID-19); IL-1beta; hyperinflammatory syndrome
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Endocrine System Diseases; COVID-19; Coronavirus Infections; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 2020-02008; me20Donath2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No