Canakinumab in Patients With COVID-19 and Type 2 Diabetes

University Hospital, Basel, Switzerland116 enrolled

Overview

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).

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

116

Conditions

Coronavirus Infection Diabetes Mellitus, Type 2

Interventions

CanakinumabDRUG

Body weight adjusted dose in 250 ml 5% dextrose solution i.v. over 2 hours

PlaceboDRUG

Aqua ad injectabilia in 250 ml 5% dextrose solution i.v. over 2 hours

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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-

Locations (9)

University Medical Clinic Aarau

Aarau, Switzerland

University Hospital Basel

Basel, Switzerland

University Hospital Bern

Bern, Switzerland

Hopital du Jura

Delémont, Switzerland

Outcomes

Primary Outcomes

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): 1. longer survival time 2. longer ventilation-free time 3. longer ICU-free time 4. 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 Outcomes

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: 1. not hospitalized with resumption of normal activities; 2. not hospitalized, but unable to resume normal activities; 3. hospitalized, not requiring supplemental oxygen; 4. hospitalized, requiring supplemental oxygen; 5. hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6. hospitalized, requiring extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, or both; and 7. death"

Time frame: From randomization up to 4 weeks

Death rate

Death rate during the 4-week period after study treatment

Time frame: 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

Time frame: 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)

Data from ClinicalTrials.gov

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