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

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

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.

Study Overview

• Status: Withdrawn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

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 Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Diabetes Research Institute, University of Miami Miller School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment Arm; 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.	Biological: ILT-101 (Aldesleukin; IL-2); Administration of Low-Dose Interleukin-2 (ILT-101) for two years; Other Names: IL-2; Interleukin-2
Experimental: Treatment-Placebo Arm; Participants in this group will receive study drug ILT-101 for one year, and then placebo for the second year.	Biological: ILT-101 (Aldesleukin; IL-2); Administration of Low-Dose Interleukin-2 (ILT-101) for two years; Other Names: IL-2; Interleukin-2; Other: Treatment-Placebo Arm; Administration of Low-Dose Interleukin-2 (ILT-101) for one year, and then placebo for the second year.
Placebo Comparator: Placebo; Participants in this group will receive a placebo injection for two years.	Other: Placebo Arm; Participants in this group will receive a placebo injection for two years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Other Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Jay S. Skyler
• Collaborators: University of Florida; University of California, San Francisco; Diabetes Research Institute Foundation
• Investigators: 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

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: July 20, 2017
• First Submitted That Met QC Criteria: August 3, 2017
• First Posted (Actual): August 8, 2017

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Diabetes; Type 1 Diabetes; IL-2; Interleukin-2; Interleukin; Autoimmune; Diabetes, Autoimmune
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Aldesleukin; Interleukin-2
• Other Study ID Numbers: 20170301 (Other Identifier: University of Miami Central IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: A participant's privacy and confidentiality will be respected throughout the study. Each participant will be assigned a unique identification number and these numbers rather than names will be used to collect, store, and report participant information. Site personnel will not transmit documents containing personal health identifiers (PHI) to the study sponsor or their representatives.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No