Canakinumab in Patients With COVID-19 and Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

— CanCovDia  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04510493
• Other study ID #: 2020-02008; me20Donath2
• Status: Completed
• Phase: Phase 3
• Start date: October 23, 2020
• Est. completion date: August 17, 2021

Study information

• Verified date: September 2021
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: August 17, 2021
• Est. primary completion date: August 17, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-

Related Conditions & MeSH terms

• Coronavirus Infection
• Coronavirus Infections
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Canakinumab
Body weight adjusted dose in 250 ml 5% dextrose solution i.v. over 2 hours
• Placebo
Aqua ad injectabilia in 250 ml 5% dextrose solution i.v. over 2 hours

Locations

Country	Name	City	State
Switzerland	University Medical Clinic Aarau	Aarau
Switzerland	University Hospital Basel	Basel
Switzerland	University Hospital Bern	Bern
Switzerland	Hopital du Jura	Delémont
Switzerland	University Hospital Geneva	Geneva
Switzerland	University Hospital Lausanne	Lausanne
Switzerland	Cantonal Hospital Lucerne	Luzern
Switzerland	Cantonal Hospital St Gallen	St. Gallen
Switzerland	University Hospital Zürich	Zürich

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	Novartis, Swiss National Science Foundation

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Death rate	Death rate during the 4-week period after study treatment	4 weeks
Secondary	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	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
Secondary	Prolonged hospital stay	Prolonged hospital stay > 3 weeks	>3 weeks
Secondary	Change in ratio to baseline in the glycated hemoglobin	Ratio to baseline in the glycated hemoglobin	Baseline, Day 29 and Day 90
Secondary	Change in ratio to baseline in the fasting glucose	Ratio to baseline in the fasting glucose	Baseline, Day 29
Secondary	Change in ratio to baseline in the fasting insulin	Ratio to baseline in the fasting insulin	Baseline, Day 29
Secondary	Change in ratio to baseline in the fasting c-peptide	Ratio to baseline in the fasting c-peptide	Baseline, Day 29
Secondary	Ratio to baseline in the C-reactive protein (CRP)	Ratio to baseline in the C-reactive protein (CRP)	Baseline, Day 29 and Day 90
Secondary	Change in ratio to baseline in the D-dimer	Ratio to baseline in the D-dimer	Baseline, Day 29
Secondary	Change in ratio to baseline in the Natriuretic peptide (NTproBNP)	Ratio to baseline in the Natriuretic peptide (NTproBNP)	Baseline, Day 29 and Day 90
Secondary	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
Secondary	Type of antidiabetic treatment at Day 29	Type of antidiabetic treatment at Day 29	Day 29
Secondary	Number of antidiabetic treatment at Day 29	Number of antidiabetic treatment at Day 29	Day 29
Secondary	Type of antidiabetic treatment at three months	Type of antidiabetic treatment at three months	Month 3
Secondary	Number of antidiabetic treatment at three months	Number of antidiabetic treatment at three months	Month 3