Canakinumab Study in Individuals With Newly Diagnosed Type 1 Diabetes

Study Overview
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Brief Summary
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Canakinumab is a fully human anti-interleukin-1β (anti-IL-1β) monoclonal antibody (IgG-1 class). Canakinumab is designed to bind to human IL-1β and to functionally neutralize the bioactivity of this pro-inflammatory cytokine. The study is a two-arm, multicenter, randomized, double-masked, placebo-controlled clinical trial. 66 subjects will be randomly assigned to receive either monthly subcutaneous injections of 2.0 mg/kg Canakinumab, or placebo for 12 months. All groups will receive standard intensive diabetes treatment with insulin and dietary management. Participants randomly assigned to Canakinumab treatment or placebo will receive a total of 12 injections over one year. All subjects will be followed for 1 year of treatment plus 1- 3 years of additional follow-up until study end. Enrollment is expected to occur over two years.

Official Title
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Effects of Canakinumab On The Progression of Type 1 Diabetes In New Onset Subjects

Conditions
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Type 1 Diabetes, Preservation of Insulin Secretion, Newly Diagnosed Type 1 Diabetes, Canakinumab in Type 1 Diabetes

Intervention / Treatment
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* Drug: canakinumab (anti IL-1beta)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between the ages of 6-45 years Be within 3-months (100 days) of diagnosis of type 1 diabetes Must have at least one diabetes-related autoantibody present Must have stimulated C-peptide levels >0.2 pmol/ml measured during a mixed meal tolerance test (MMTT) conducted at least 21 days from diagnosis and within 37 days of randomization If participant is female with reproductive potential, she must be willing to avoid pregnancy and have a negative pregnancy test during the 12 months of treatment and for an additional 3 months after completing treatment Be at least one month from time of last live immunization received Willing to forgo live vaccinations for 24 months Must be willing to comply with intensive diabetes management Must weigh at least 20 kg (44 lbs) at study entry Exclusion Criteria: Are immunodeficient or have clinically significant chronic lymphopenia (low white blood cell count) Have an active infection Have a positive PPD test result Be currently pregnant or lactating, or anticipate getting pregnant Ongoing use of medications known to influence glucose tolerance Require use of other immunosuppressive agents Have serologic evidence of current or past HIV, Hepatitis B, or Hepatitis C infection Have any complicating medical issues or abnormal clinical laboratory blood counts or results that interfere with study conduct; history of malignancies Be currently participating in another type 1 diabetes treatment study

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo solution given by subcutaneous injection on monthly basis for 12 months | Drug: Placebo<br>* Placebo subcutaneous injections<br>|
| Experimental: Canakinumab<br>Subcutaneous injection of canakinumab at dose of 2.0 mg/kg given monthly of 12 months | Drug: canakinumab (anti IL-1beta)<br>* canakinumab subcutaneous injections given at 2.0mg/kg dose on monthly basis for 12 months<br>* Other names: anti IL-1beta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-peptide Response to Mixed Meal Glucose Tolerance Test (MMTT) at One Year for Subjects Given Canakinumab Compared to Placebo | The primary outcome is the area under the stimulated C-peptide curve (AUC) based on data collected at time 0 to 2 hours of a 4-hour mixed meal glucose tolerance test (MMTT) conducted at the primary endpoint visit. The timed measurements are done at: 0, 15, 30 60, 90, and 120 minutes. The calculation for the concentration of c-peptide is a weighted average of the 6 timed measurements of c-peptide in nano-moles/Liter. We try to distinguish this calculation from the AUC by referring to it as the AUC mean and may be expressed algebraically as the AUC/(120 min.); thus, the units are the same as the y-axis. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 1 diabetes, newly diagnosed T1D, T1D, canakinumab, anti IL-1