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

NCT ID: NCT03243058

Last Updated: 2024-05-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1/PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-30

Study Completion Date

2028-12-31

Brief Summary

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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

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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.

Conditions

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Diabetes Mellitus, Type 1 Diabetes Diabetes, Autoimmune

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
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.

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

ILT-101 (Aldesleukin; IL-2)

Intervention Type BIOLOGICAL

Administration of Low-Dose Interleukin-2 (ILT-101) for two years

Treatment-Placebo Arm

Participants in this group will receive study drug ILT-101 for one year, and then placebo for the second year.

Group Type EXPERIMENTAL

ILT-101 (Aldesleukin; IL-2)

Intervention Type BIOLOGICAL

Administration of Low-Dose Interleukin-2 (ILT-101) for two years

Treatment-Placebo Arm

Intervention Type OTHER

Administration of Low-Dose Interleukin-2 (ILT-101) for one year, and then placebo for the second year.

Placebo

Participants in this group will receive a placebo injection for two years.

Group Type PLACEBO_COMPARATOR

Placebo Arm

Intervention Type OTHER

Participants in this group will receive a placebo injection for two years.

Interventions

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ILT-101 (Aldesleukin; IL-2)

Administration of Low-Dose Interleukin-2 (ILT-101) for two years

Intervention Type BIOLOGICAL

Treatment-Placebo Arm

Administration of Low-Dose Interleukin-2 (ILT-101) for one year, and then placebo for the second year.

Intervention Type OTHER

Placebo Arm

Participants in this group will receive a placebo injection for two years.

Intervention Type OTHER

Other Intervention Names

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IL-2 Interleukin-2

Eligibility Criteria

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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
Minimum Eligible Age

8 Years

Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Diabetes Research Institute Foundation

OTHER

Sponsor Role collaborator

University of Florida

OTHER

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role collaborator

Jay S. Skyler

OTHER

Sponsor Role lead

Responsible Party

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Jay S. Skyler

Professor of Medicine

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Jay S Skyler, M.D.

Role: PRINCIPAL_INVESTIGATOR

Professor of Medicine

Alberto Pugliese, M.D.

Role: PRINCIPAL_INVESTIGATOR

Professor of Medicine

David A Baidal, M.D.

Role: PRINCIPAL_INVESTIGATOR

Assistant Professor of Medicine

Locations

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Diabetes Research Institute, University of Miami Miller School of Medicine

Miami, Florida, United States

Site Status

Countries

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United States

Other Identifiers

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20170301

Identifier Type: OTHER

Identifier Source: secondary_id

20170301

Identifier Type: -

Identifier Source: org_study_id

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