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

Phase 1

Withdrawn

• Conditions: Diabetes, Autoimmune; Diabetes Mellitus, Type 1; Diabetes
• Interventions: Biological: ILT-101 (Aldesleukin; IL-2); Other: Placebo Arm; Other: Treatment-Placebo Arm

• Registration Number: NCT03243058
• Lead Sponsor: Jay S. Skyler

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.

Study Timeline

• Study First Submitted: 2017-07-20
• Study First Submitted QC: 2017-08-03
• Study First Posted: 2017-08-08
• Study Start: 2023-06
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-20
• Last Update Posted: 2024-05-22
• Primary Completion: 2026-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Arm	ILT-101 (Aldesleukin; IL-2)	ILT-101 (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 two years.
Treatment-Placebo Arm	ILT-101 (Aldesleukin; IL-2)	Participants in this group will receive study drug ILT-101 for one year, and then placebo for the second year.
Treatment-Placebo Arm	Treatment-Placebo Arm	Participants in this group will receive study drug ILT-101 for one year, and then placebo for the second year.
Placebo	Placebo Arm	Participants in this group will receive a placebo injection for two years.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Diabetes Research Institute, University of Miami Miller School of Medicine; 🇺🇸 Miami, Florida, United States