Diabetes, Diabetes, Autoimmune, Diabetes Mellitus, Type 1
Conditions
Keywords
Diabetes, Type 1 Diabetes, Autoimmune, Diabetes, Autoimmune, Interleukin-2, Interleukin, IL-2
Brief summary
Randomized, controlled, double-blinded, multicenter, phase I/II clinical trial to evaluate the safety of low-dose IL-2 and determine whether low-dose IL-2 therapy for one year, can prevent further loss of beta-cell function in patients with established T1D, (primary outcome). The study will carefully examine various effects of low-dose IL-2 on the immune system in patients with T1D, including effects on Treg and other cell subsets, and disease-specific autoimmune responses.
Detailed description
Randomized, controlled, double-blinded, multicenter, phase I/II clinical trial to evaluate the safety of low-dose IL-2 and determine whether low-dose IL-2 therapy for one year, can prevent further loss of beta-cell function in patients with established T1D, (primary outcome). The study will carefully examine various effects of low-dose IL-2 on the immune system in patients with T1D, including effects on Treg and other cell subsets, and disease-specific autoimmune responses. Patients will be treated with ILT-101 or placebo. ILT-101 will be given at doses of 0.5 million IU (body surface area \<2 m2) or 1 million IU (body surface area \>2 m2), via subcutaneous (s.c.) injections. Patients will receive a course of 5 daily injections (days 1-5. Starting on day 15, patients will receive an s.c. injection (same dose) every 15 days for 1 year. Thus, patients will receive 29 injections during the first year of treatment. At the end of the first year, approximately half of those randomized to ILT-101 will continue receiving treatment every 15 days, until the end of the second year (23 doses). The other half will stop therapy and will be switched to a placebo. A group of patients will be randomly assigned to a placebo for the duration of the study. Patients to be included in this study are those diagnosed with T1D who would have had T1D from 4 months to 1 year at the time of randomization, who have a current or past demonstration of autoimmunity (using autoantibodies), and maintain preserved β-cell function, defined as an MMTT stimulated C-peptide \>0.2 nmol/L. This population is chosen because it will extend the scope of therapy beyond the immediate time following diagnosis when most previous studies of immunotherapy in T1D have been conducted. This trial can further impact the field if a therapeutic benefit is shown when the disease is more established.
Interventions
BIOLOGICALILT-101 (Aldesleukin; IL-2)
Administration of Low-Dose Interleukin-2 (ILT-101) for two years
OTHERTreatment-Placebo Arm
Administration of Low-Dose Interleukin-2 (ILT-101) for one year, and then placebo for the second year.
OTHERPlacebo Arm
Participants in this group will receive a placebo injection for two years.
Sponsors
Diabetes Research Institute Foundation
University of Florida
University of California, San Francisco
Jay S. Skyler
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
The randomization will be performed by the Coordinating Center at the University of Miami. The participants will not be informed regarding the intervention assignment until the end of the study. The investigators and clinic personnel will also be masked as to study assignment. Laboratories performing assays for this protocol will be masked as to the identity and group assignment of biological materials to be studied.
Intervention model description
ILT-101 (aldesleukin; Interleukin-2, IL-2), 0.5 million IU (body surface area \<2 m2) or 1 million IU (body surface area \>2 m2), or placebo, will be given for 5 consecutive days (days 1-5), and then on day 15 and every 15 days thereafter, for one year; at the one-year endpoint, approximately half the subjects on ILT-101 will continue therapy and the other half will switch to placebo for 1 more year.
Eligibility
Sex/Gender
ALL
Age
8 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* 8-21 years of age * T1D, demonstrated by at least one islet autoantibody * T1D duration 4-12 months at the time of the first dose * Peak stimulated C-peptide \>0.2 nmol/L during a 4-hour MMTT
Exclusion criteria
* Treatment with oral anti-diabetic agents * Illnesses that would preclude use of low-dose IL-2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| C-peptide response | 1 year primary outcome | Preservation of insulin secretion (measured as c-peptide nmol/L) based on stimulated area under the curve (AUC) during a 4-hour MMTT at 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| C-peptide response | 2 year secondary outcome | Preservation of insulin secretion (measured as c-peptide nmol/L) based on stimulated area under the curve (AUC) during a 4-hour MMTT at 2 years |
Other
| Measure | Time frame |
|---|---|
| Proportions of regulatory T cells at (a) 1 year, (b) 2 years | 1 Year and 2 Years |
| Changes in insulin requirements | 1 Year and 2 Years |
| HbA1c level | 1 Year and 2 Years |
Countries
United States
Outcome results
None listed