Clinical trial NCT03243058: Low-dose IL-2 in Established T1D - The "PROREG" Study
Official title: A Randomized, Double Blind, Phase I/II Trial of Low-Dose Interlekin-2 Immunotherapy in Established Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Diabetes Mellitus, Type 1
Diabetes
Diabetes, Autoimmune
Keywords: Diabetes
Type 1 Diabetes
Autoimmune
Diabetes, Autoimmune
Interleukin-2
Interleukin
IL-2
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: Diabetes Research Institute Foundation
name: University of Florida
name: University of California, San Francisco
First posted: 2017-08-08
Enrollment: 0
Sex: ALL
Minimum age (years): 8
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: C-peptide response
timeFrame: 1 year primary outcome
Secondary outcomes:
measure: C-peptide response
timeFrame: 2 year secondary outcome
Other outcomes:
measure: Proportions of regulatory T cells at (a) 1 year, (b) 2 years
timeFrame: 1 Year and 2 Years
measure: Changes in insulin requirements
timeFrame: 1 Year and 2 Years
measure: HbA1c level
timeFrame: 1 Year and 2 Years
Locations:
city: Miami
country: United States
facility: Diabetes Research Institute, University of Miami Miller School of Medicine
state: Florida
Study officials:
affiliation: Professor of Medicine
name: Jay S Skyler, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Professor of Medicine
name: Alberto Pugliese, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistant Professor of Medicine
name: David A Baidal, M.D.
role: PRINCIPAL_INVESTIGATOR
References: