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

Sponsor

University Hospital, Basel, Switzerland (Other)

Overall Status

Completed

CT.gov ID

NCT04510493

Collaborator

Novartis (Industry), Swiss National Science Foundation (Other)

116

Enrollment

Locations

Arms

9.8

Actual Duration (Months)

12.9

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

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

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 :

Oct 23, 2020

Actual Primary Completion Date :

Aug 17, 2021

Actual Study Completion Date :

Aug 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 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

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

Outcome Measures

Primary Outcome Measures

unmatched win ratio after treatment with canakinumab compared to Placebo (composite endpoint) [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): 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.

Secondary Outcome Measures

Time to clinical improvement [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: 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"
Death rate [4 weeks]
Death rate during the 4-week period after study treatment
Admission to intensive care unit (ICU) [4 weeks]
Admission to the intensive care unit from the medical ward during the 4-week period after study treatment
Secondary worsening of disease [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 [>3 weeks]
Prolonged hospital stay > 3 weeks
Change in ratio to baseline in the glycated hemoglobin [Baseline, Day 29 and Day 90]
Ratio to baseline in the glycated hemoglobin
Change in ratio to baseline in the fasting glucose [Baseline, Day 29]
Ratio to baseline in the fasting glucose
Change in ratio to baseline in the fasting insulin [Baseline, Day 29]
Ratio to baseline in the fasting insulin
Change in ratio to baseline in the fasting c-peptide [Baseline, Day 29]
Ratio to baseline in the fasting c-peptide
Ratio to baseline in the C-reactive protein (CRP) [Baseline, Day 29 and Day 90]
Ratio to baseline in the C-reactive protein (CRP)
Change in ratio to baseline in the D-dimer [Baseline, Day 29]
Ratio to baseline in the D-dimer
Change in ratio to baseline in the Natriuretic peptide (NTproBNP) [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) [Baseline, Day 29 and Day 90]
Ratio to baseline in the Glomerular Filtration Rate Renal (eGFR)
Type of antidiabetic treatment at Day 29 [Day 29]
Type of antidiabetic treatment at Day 29
Number of antidiabetic treatment at Day 29 [Day 29]
Number of antidiabetic treatment at Day 29
Type of antidiabetic treatment at three months [Month 3]
Type of antidiabetic treatment at three months
Number of antidiabetic treatment at three months [Month 3]
Number of antidiabetic treatment at three months

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	Country	Postal Code
1	University Medical Clinic Aarau	Aarau	Switzerland	5001
2	University Hospital Basel	Basel	Switzerland	4031
3	University Hospital Bern	Bern	Switzerland	3010
4	Hopital du Jura	Delémont	Switzerland	2800
5	University Hospital Geneva	Geneva	Switzerland	1205
6	University Hospital Lausanne	Lausanne	Switzerland	1011
7	Cantonal Hospital Lucerne	Luzern	Switzerland	6004
8	Cantonal Hospital St Gallen	St. Gallen	Switzerland	9001
9	University Hospital Zürich	Zürich	Switzerland	8091