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

Primary Purpose

Coronavirus Infection, Diabetes Mellitus, Type 2

Status
Completed
Phase
Phase 3
Locations
Switzerland
Study Type
Interventional
Intervention
Canakinumab
Placebo
Sponsored by
University Hospital, Basel, Switzerland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronavirus Infection focused on measuring NLRP3, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Coronavirus Disease 19 (COVID-19), IL-1beta, hyperinflammatory syndrome, obesity

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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-

Sites / Locations

  • University Medical Clinic Aarau
  • University Hospital Basel
  • University Hospital Bern
  • Hopital du Jura
  • University Hospital Geneva
  • University Hospital Lausanne
  • Cantonal Hospital Lucerne
  • Cantonal Hospital St Gallen
  • University Hospital Zürich

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

active treatment arm

placebo treatment arm

Arm Description

Treatment with Canakinumab i.v. administered over 2 hours

placebo treatment

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
August 11, 2020
Last Updated
September 7, 2021
Sponsor
University Hospital, Basel, Switzerland
Collaborators
Novartis, Swiss National Science Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT04510493
Brief Title
Canakinumab in Patients With COVID-19 and Type 2 Diabetes
Acronym
CanCovDia
Official Title
Canakinumab in Patients With COVID-19 and Type 2 Diabetes - CanCovDia Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
October 23, 2020 (Actual)
Primary Completion Date
August 17, 2021 (Actual)
Study Completion Date
August 17, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland
Collaborators
Novartis, Swiss National Science Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
116 (Actual)

8. Arms, Groups, and Interventions

Arm Title
active treatment arm
Arm Type
Active Comparator
Arm Description
Treatment with Canakinumab i.v. administered over 2 hours
Arm Title
placebo treatment arm
Arm Type
Placebo Comparator
Arm Description
placebo treatment
Intervention Type
Drug
Intervention Name(s)
Canakinumab
Other Intervention Name(s)
Ilaris®
Intervention Description
Body weight adjusted dose in 250 ml 5% dextrose solution i.v. over 2 hours
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Aqua ad injectabilia in 250 ml 5% dextrose solution
Intervention Description
Aqua ad injectabilia in 250 ml 5% dextrose solution i.v. over 2 hours
Primary Outcome Measure Information:
Title
unmatched win ratio after treatment with canakinumab compared to Placebo (composite endpoint)
Description
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.
Time Frame
within 4 weeks after treatment with canakinumab or placebo
Secondary Outcome Measure Information:
Title
Time to clinical improvement
Description
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"
Time Frame
From randomization up to 4 weeks
Title
Death rate
Description
Death rate during the 4-week period after study treatment
Time Frame
4 weeks
Title
Admission to intensive care unit (ICU)
Description
Admission to the intensive care unit from the medical ward during the 4-week period after study treatment
Time Frame
4 weeks
Title
Secondary worsening of disease
Description
Secondary worsening of disease (i.e., development of Acute respiratory distress Syndrome (ARDS), increase of oxygen demand after 72h of treatment)
Time Frame
4 weeks
Title
Prolonged hospital stay
Description
Prolonged hospital stay > 3 weeks
Time Frame
>3 weeks
Title
Change in ratio to baseline in the glycated hemoglobin
Description
Ratio to baseline in the glycated hemoglobin
Time Frame
Baseline, Day 29 and Day 90
Title
Change in ratio to baseline in the fasting glucose
Description
Ratio to baseline in the fasting glucose
Time Frame
Baseline, Day 29
Title
Change in ratio to baseline in the fasting insulin
Description
Ratio to baseline in the fasting insulin
Time Frame
Baseline, Day 29
Title
Change in ratio to baseline in the fasting c-peptide
Description
Ratio to baseline in the fasting c-peptide
Time Frame
Baseline, Day 29
Title
Ratio to baseline in the C-reactive protein (CRP)
Description
Ratio to baseline in the C-reactive protein (CRP)
Time Frame
Baseline, Day 29 and Day 90
Title
Change in ratio to baseline in the D-dimer
Description
Ratio to baseline in the D-dimer
Time Frame
Baseline, Day 29
Title
Change in ratio to baseline in the Natriuretic peptide (NTproBNP)
Description
Ratio to baseline in the Natriuretic peptide (NTproBNP)
Time Frame
Baseline, Day 29 and Day 90
Title
Change in ratio to baseline in the Glomerular Filtration Rate Renal (eGFR)
Description
Ratio to baseline in the Glomerular Filtration Rate Renal (eGFR)
Time Frame
Baseline, Day 29 and Day 90
Title
Type of antidiabetic treatment at Day 29
Description
Type of antidiabetic treatment at Day 29
Time Frame
Day 29
Title
Number of antidiabetic treatment at Day 29
Description
Number of antidiabetic treatment at Day 29
Time Frame
Day 29
Title
Type of antidiabetic treatment at three months
Description
Type of antidiabetic treatment at three months
Time Frame
Month 3
Title
Number of antidiabetic treatment at three months
Description
Number of antidiabetic treatment at three months
Time Frame
Month 3

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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-
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Donath, MD, Prof.
Organizational Affiliation
University Hospital Basel, Department of Endocrinology, Diabetes and Metabolism
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Medical Clinic Aarau
City
Aarau
ZIP/Postal Code
5001
Country
Switzerland
Facility Name
University Hospital Basel
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
Facility Name
University Hospital Bern
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
Hopital du Jura
City
Delémont
ZIP/Postal Code
2800
Country
Switzerland
Facility Name
University Hospital Geneva
City
Geneva
ZIP/Postal Code
1205
Country
Switzerland
Facility Name
University Hospital Lausanne
City
Lausanne
ZIP/Postal Code
1011
Country
Switzerland
Facility Name
Cantonal Hospital Lucerne
City
Luzern
ZIP/Postal Code
6004
Country
Switzerland
Facility Name
Cantonal Hospital St Gallen
City
St. Gallen
ZIP/Postal Code
9001
Country
Switzerland
Facility Name
University Hospital Zürich
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
36128334
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.
Results Reference
derived

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Canakinumab in Patients With COVID-19 and Type 2 Diabetes

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