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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03243058
Recruitment Status : Suspended (Funding withdrawal and COVID-19 environment.)
First Posted : August 8, 2017
Last Update Posted : June 5, 2020
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
Diabetes Research Institute Foundation
University of Florida
University of California, San Francisco
Information provided by (Responsible Party):
Jay S. Skyler, University of Miami

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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Diabetes Diabetes, Autoimmune Biological: ILT-101 (Aldesleukin; IL-2) Other: Treatment-Placebo Arm Other: Placebo Arm Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.
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.
Primary Purpose: Treatment
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 2021
Estimated Primary Completion Date : August 2025
Estimated Study Completion Date : October 2025

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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


Other Outcome Measures:
  1. Proportions of regulatory T cells at (a) 1 year, (b) 2 years [ Time Frame: 1 Year and 2 Years ]
  2. Changes in insulin requirements [ Time Frame: 1 Year and 2 Years ]
  3. HbA1c level [ Time Frame: 1 Year and 2 Years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   8 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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


Locations
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United States, Florida
Diabetes Research Institute, University of Miami Miller School of Medicine
Miami, Florida, United States, 33136
Sponsors and Collaborators
Jay S. Skyler
National Institute of Allergy and Infectious Diseases (NIAID)
Diabetes Research Institute Foundation
University of Florida
University of California, San Francisco
Investigators
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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
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Responsible Party: Jay S. Skyler, Professor of Medicine, University of Miami
ClinicalTrials.gov Identifier: NCT03243058    
Other Study ID Numbers: 20170301
20170301 ( Other Identifier: University of Miami Central IRB )
First Posted: August 8, 2017    Key Record Dates
Last Update Posted: June 5, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jay S. Skyler, University of Miami:
Diabetes
Type 1 Diabetes
Autoimmune
Diabetes, Autoimmune
Interleukin-2
Interleukin
IL-2
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Aldesleukin
Interleukin-2
Antineoplastic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents