Clinical trial NCT04510493: Canakinumab in Patients With COVID-19 and Type 2 Diabetes
Official title: Canakinumab in Patients With COVID-19 and Type 2 Diabetes - CanCovDia Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Coronavirus Infection
Diabetes Mellitus, Type 2
Keywords: NLRP3
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Coronavirus Disease 19 (COVID-19)
IL-1beta
hyperinflammatory syndrome
obesity
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Novartis
name: Swiss National Science Foundation
First posted: 2020-08-12
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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-

Primary outcomes:
measure: unmatched win ratio after treatment with canakinumab compared to Placebo (composite endpoint)
timeFrame: within 4 weeks after treatment with canakinumab or placebo
Secondary outcomes:
measure: Time to clinical improvement
timeFrame: From randomization up to 4 weeks
measure: Death rate
timeFrame: 4 weeks
measure: Admission to intensive care unit (ICU)
timeFrame: 4 weeks
measure: Secondary worsening of disease
timeFrame: 4 weeks
measure: Prolonged hospital stay
timeFrame: >3 weeks
measure: Change in ratio to baseline in the glycated hemoglobin
timeFrame: Baseline, Day 29 and Day 90
measure: Change in ratio to baseline in the fasting glucose
timeFrame: Baseline, Day 29
measure: Change in ratio to baseline in the fasting insulin
timeFrame: Baseline, Day 29
measure: Change in ratio to baseline in the fasting c-peptide
timeFrame: Baseline, Day 29
measure: Ratio to baseline in the C-reactive protein (CRP)
timeFrame: Baseline, Day 29 and Day 90
measure: Change in ratio to baseline in the D-dimer
timeFrame: Baseline, Day 29
measure: Change in ratio to baseline in the Natriuretic peptide (NTproBNP)
timeFrame: Baseline, Day 29 and Day 90
measure: Change in ratio to baseline in the Glomerular Filtration Rate Renal (eGFR)
timeFrame: Baseline, Day 29 and Day 90
measure: Type of antidiabetic treatment at Day 29
timeFrame: Day 29
measure: Number of antidiabetic treatment at Day 29
timeFrame: Day 29
measure: Type of antidiabetic treatment at three months
timeFrame: Month 3
measure: Number of antidiabetic treatment at three months
timeFrame: Month 3
Other outcomes:
Locations:
city: Aarau
country: Switzerland
facility: University Medical Clinic Aarau
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Bern
country: Switzerland
facility: University Hospital Bern
city: Delémont
country: Switzerland
facility: Hopital du Jura
city: Geneva
country: Switzerland
facility: University Hospital Geneva
city: Lausanne
country: Switzerland
facility: University Hospital Lausanne
city: Luzern
country: Switzerland
facility: Cantonal Hospital Lucerne
city: St. Gallen
country: Switzerland
facility: Cantonal Hospital St Gallen
city: Zürich
country: Switzerland
facility: University Hospital Zürich
Study officials:
affiliation: University Hospital Basel, Department of Endocrinology, Diabetes and Metabolism
name: Marc Donath, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.