Low-dose IL-2 in Established T1D - The "PROREG" Study

Diabetes Clinical Trial

Official title:

A Randomized, Double Blind, Phase I/II Trial of Low-Dose Interlekin-2 Immunotherapy in Established Type 1 Diabetes

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03243058
• Other study ID #: 20170301
• Secondary ID: 20170301
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: June 2023
• Est. completion date: December 2028

Study information

• Verified date: November 2023
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2028
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetes, Autoimmune

Intervention

Biological:
• ILT-101 (Aldesleukin; IL-2)
Administration of Low-Dose Interleukin-2 (ILT-101) for two years

Other:
• Treatment-Placebo Arm
Administration of Low-Dose Interleukin-2 (ILT-101) for one year, and then placebo for the second year.
• Placebo Arm
Participants in this group will receive a placebo injection for two years.

Locations

Country	Name	City	State
United States	Diabetes Research Institute, University of Miami Miller School of Medicine	Miami	Florida

Sponsors (4)

Lead Sponsor	Collaborator
Jay S. Skyler	Diabetes Research Institute Foundation, University of California, San Francisco, University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportions of regulatory T cells at (a) 1 year, (b) 2 years		1 Year and 2 Years
Other	Changes in insulin requirements		1 Year and 2 Years
Other	HbA1c level		1 Year and 2 Years
Primary	C-peptide response	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	1 year primary outcome
Secondary	C-peptide response	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	2 year secondary outcome