Canakinumab in Type 1 Diabetes, Newly Diagnosed Type 1 Diabetes, Preservation of Insulin Secretion, Type 1 Diabetes
Conditions
Keywords
type 1 diabetes, newly diagnosed T1D, T1D, canakinumab, anti IL-1
Brief summary
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.
Interventions
DRUGcanakinumab (anti IL-1beta)
canakinumab subcutaneous injections given at 2.0mg/kg dose on monthly basis for 12 months
DRUGPlacebo
Placebo subcutaneous injections
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| C-peptide Response to Mixed Meal Glucose Tolerance Test (MMTT) at One Year for Subjects Given Canakinumab Compared to Placebo | 12 months | 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. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Injection Placebo solution (2.0/kg dose) given subcutaneously on monthly basis for 12 months | 22 |
| Canakinumab (Anti IL-1beta) canakinumab (anti IL-1beta): canakinumab subcutaneous injections given at 2.0mg/kg dose on monthly basis for 12 months | 49 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Placebo Injection | Canakinumab (Anti IL-1beta) | Total |
|---|---|---|---|
| Age, Continuous | 12.4 years STANDARD_DEVIATION 6.4 | 11.6 years STANDARD_DEVIATION 4 | 11.8 years STANDARD_DEVIATION 4.8 |
| Sex: Female, Male Female | 8 Participants | 25 Participants | 33 Participants |
| Sex: Female, Male Male | 14 Participants | 24 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 22 | 30 / 49 |
| serious Total, serious adverse events | 1 / 22 | 1 / 49 |
Outcome results
Primary
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.
Time frame: 12 months
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo Injection | C-peptide Response to Mixed Meal Glucose Tolerance Test (MMTT) at One Year for Subjects Given Canakinumab Compared to Placebo | 0.40 nmol/L |
| Canakinumab (Anti IL-1beta) | C-peptide Response to Mixed Meal Glucose Tolerance Test (MMTT) at One Year for Subjects Given Canakinumab Compared to Placebo | 0.41 nmol/L |
p-value: 0.86ANCOVA