Administration of Low-dose IL-2 in Established T1D (IL-2)
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|ClinicalTrials.gov Identifier: NCT03243058|
Recruitment Status : Not yet recruiting
First Posted : August 8, 2017
Last Update Posted : July 12, 2018
|Condition or disease||Intervention/treatment||Phase|
|Diabetes Mellitus, Type 1 Diabetes Diabetes, Autoimmune||Drug: Proleukin® (Aldesleukin; IL-2) Drug: Placebo - Concentrate||Phase 1 Phase 2|
This will be a randomized, controlled, double blinded, multicenter, phase I/II clinical trial to evaluate the safety of low-dose IL-2 and to test whether low-dose IL-2 can prevent further loss of beta-cell function in patients with established T1D, or even potentially improve ß-cell function in such individuals, when IL-2 is given for one year (primary outcome). Equally important, 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 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 current or past demonstration of autoimmunity (using autoantibodies), and maintain preserved beta-cell function, defined as a 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, and impact the field if a therapeutic benefit can be shown when the disease is more established.
Potential participants will have a screening visit to review overall health, measure diabetes T1D-associated autoantibodies and perform a MMTT, which will also serve as the baseline MMTT. Eligible subjects will be invited to participate in the intervention trial and randomized to treatment with Proleukin® or placebo. Fifty-four patients will be enrolled, aged 12-21 years, both genders, and randomized to treatment or placebo in a 2:1 ratio. Participation for each subject will last approximately 2 years. The 18 patients randomized to the control arm will receive placebo for two years. At the end of the first year, the 36 patients randomized to the treatment arm will be randomized 1:1 to continued treatment or placebo. Thus, among the 36 patients who received treatment during the first year, 18 patients will continue therapy and 18 patients will switch to placebo until the end of the study. This study design allows examining safety and efficacy at one year (primary outcome), and further evaluates these parameters after the therapy has stopped or it is continued up to the end of 2 years (secondary outcome).
The clinical investigator(s) will evaluate beta-cell function by examining C-peptide response during a MMTT, and using glucose and C-peptide data obtained during the MMTTs investigator(s) will determine beta-cell sensitivity to glucose, insulin sensitivity, and insulin secretion using the Mari model (99). It is documented that ß-cells in T1D are "blind" to glucose, by showing reduced ß-cell sensitivity to glucose using the Mari model in relatives at risk of T1D (100). The extent, to which this may account for reduced ß-cell function, and whether this is to any degree reversible, is unknown. Thus, clinical investigator(s) will characterize ß-cell function in response to low-dose IL-2 by measuring insulin secretion during a 4-hour MMTT, and using the Mari model to calculate ß-cell sensitivity to glucose and insulin sensitivity/resistance.
In other trials with low-dose IL-2, risks have been minimal compared to the well-known side effects of high dose IL-2. Risks of low-dose IL-2 include some potential side effects, such as pain or skin reactions at the injection site, with potential discomfort, redness, swelling, or even a scab at the injection site; flu-like symptoms, nausea, and diarrhea. Unexpected risks are always possible.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||54 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Eligible subjects will be invited to participate in the intervention trial and randomized to treatment with Proleukin® or placebo. Fifty-four patients will be enrolled, aged 12-21 years, both genders, and randomized to treatment or placebo in a 2:1 ratio. Participation for each subject will last approximately 2 years. The 18 patients randomized to the control arm will receive placebo for two years. At the end of the first year, the 36 patients randomized to the treatment arm will be randomized 1:1 to continued treatment or placebo. Thus, among the 36 patients who received treatment during the first year, 18 patients will continue therapy and 18 patients will switch to placebo until the end of the study.|
|Masking:||Triple (Participant, Care Provider, 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.|
|Official Title:||A Randomized, Double Blind, Phase I/II Trial of Low-Dose Interlekin-2 Immunotherapy in Established Type 1 Diabetes|
|Estimated Study Start Date :||December 2018|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||December 2024|
Active Comparator: Treatment Arm
Proleukin® (Aldesleukin; IL-2), 0.5 million IU/m2 (up to a maximum of 1 million IU), 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, subjects in the treatment arm will be randomized 1:1 to continued therapy or switched to placebo, for 1 more year.
Drug: Proleukin® (Aldesleukin; IL-2)
Administration of Low-Dose Interleukin
Other Name: IL-2
Placebo Comparator: Control Arm
18 patients will be randomized to the control arm and will receive placebo for two years.
Drug: Placebo - Concentrate
Randomized Placebo group will be administered subcutaneously
- C-peptide response [ Time Frame: 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
- C-peptide response [ Time Frame: 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
- Proportions of regulatory T cells at (a) 1 year, (b) 2 years [ Time Frame: 1 Year and 2 Years ]
- Changes in insulin requirements [ Time Frame: 1 Year and 2 Years ]
- HbA1c level [ Time Frame: 1 Year and 2 Years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03243058
|Contact: Alberto Pugliese, M.D.||firstname.lastname@example.org|
|Principal Investigator:||Jay S Skyler, M.D.||Professor of Medicine|
|Principal Investigator:||Alberto Pugliese, M.D.||Professor of Medicine|
|Principal Investigator:||David A Baidal, M.D.||Assistant Professor of Medicine|