T1DM Immunotherapy Using Polyclonal Tregs + IL-2

NCT02772679 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 16-19632
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to assess the safety of Tregs + IL-2 and survival of Tregs in patients with recent onset T1DM who receive infusions of autologous Tregs + IL-2.

Conditions

Type 1 Diabetes Mellitus

Keywords

Diabetes; Treg; Proluekin

Outcome Measures

Primary Outcomes (2)

• Adverse events

  Adverse events of special interest: including infections, malignancies, safety of Treg infusions, and local and systemic reactions to IL-2.

  up to 3 years

• Survival of Tregs

  Comparison of the survival of graded doses of Tregs and IL-2. Calculating the half-life of infused deuterium-labeled Tregs in peripheral circulation will be used to assess the survival of Tregs.

  up to 3 years

Secondary Outcomes (9)

• C-peptide response

  up to 3 years

• Insulin use

  up to 3 years

• HbA1c levels

  up to 3 years

• Severe hypoglycemic events

  up to 3 years

• Proportion of subjects who achieve at least a 13-week reduction in insulin dose to < 0.5 units/kg in each treatment arm

  up to 3 years

Study Arms (1)

PolyTregs+IL-2

EXPERIMENTAL

Patients with type 1 diabetes mellitus will receive ex vivo expanded human autologous polyclonal regulatory T cells plus IL-2

Biological: PolyTregs+IL-2

Interventions

PolyTregs+IL-2 BIOLOGICAL

PolyTregs will be infused into the patient in a single infusion. The first cohort will receive 3 x10\^6 cells. The second cohort will receive 20x10\^6 cells. Following the day 0 infusion of polyclonal Tregs, subjects will receive two 5-day courses of IL-2 (1 x 106 IU daily), the first on days 3-7 and the second on days 38-42. Administration of the second course of IL-2 may be delayed or withheld depending on threshold criteria for peripheral blood Treg frequencies and MMTT-stimulated C-peptide levels determined on day 28.

PolyTregs+IL-2

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of T1DM within \>3 and \<24 months of day 0 according to the American Diabetes Association standard criteria.
• to 45 years of age on day of screening visit.
• Positive for at least one islet cell autoantibody (glutamate decarboxylase; insulin, if obtained within 10 days of the onset of insulin therapy; ICA 512-antibody; and/or ZnT8).
• Peak stimulated C-peptide level \>0.2 pmol/mL (0.6 ng/ml) following an MMTT.
• Weight of \>= 40 kg and \<=90.7kg
• Adequate venous access to support a blood draw of 5 mls/kg up to maximum of 400 ml whole blood and later infusion of investigational therapy

You may not qualify if:

• Hemoglobin \<10.0 g/dL; leukocytes \<3,000/μL; neutrophils \<1,500/μL; lymphocytes \<800μL; platelets \<100,000/μL
• Any sign of significant chronic active infection (e.g., hepatitis, tuberculosis, EBV, or CMV), or screening laboratory evidence consistent with a significant chronic active infection (such as positive for HIV, PPD, or HBsAg).
• Anticipated ongoing use of diabetes medications other than insulin that affect glucose homeostasis, such as metformin, sulfonylureas, thiazolidinediones, glucagon-like peptide 1 (GLP-1) mimetics, dipeptidyl peptidase IV (DPP-IV) inhibitors, SGLT2 inhibitors, or amylin.
• Chronic use of systemic glucocorticoids or other immunosuppressive agents, or biologic immunomodulators within 6 months prior to study entry. Specifically, subjects who have received over 7 days of treatment with 7.5 mg of prednisone (or the equivalent) within 6 months prior to study entry will be excluded.
• History of malignancy (including squamous cell carcinoma of the skin or cervix) except adequately treated basal cell carcinoma
• Pregnant or breastfeeding women, or any female who is unwilling to use a reliable and effective form of contraception for 1 year after Treg +/- IL-2 dosing, and any male who is unwilling to use a reliable and effective form of contraception for 3 months after Treg +/- IL-2 dosing
• Any condition that, in the investigator's opinion, may compromise study participation or may confound the interpretation of the study results.
• Patients who are unwilling to agree to not participate in another clinical trial, which in the opinion of the investigator may confound the results of this study, for at least 1 year following Treg infusion.

Sponsors & Collaborators

• Jeffrey Bluestone: lead
• Yale University: collaborator

Study Sites (2)

University of California, San Francisco Medical Center

San Francisco, California, 94143, United States

Location

Yale University

New Haven, Connecticut, 06519, United States

Location

Related Publications (35)

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• Bluestone JA, Buckner JH, Fitch M, Gitelman SE, Gupta S, Hellerstein MK, Herold KC, Lares A, Lee MR, Li K, Liu W, Long SA, Masiello LM, Nguyen V, Putnam AL, Rieck M, Sayre PH, Tang Q. Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Sci Transl Med. 2015 Nov 25;7(315):315ra189. doi: 10.1126/scitranslmed.aad4134.

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  PMID: 34324441 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 10, 2016
• First Posted: May 13, 2016
• Study Start: August 1, 2016
• Primary Completion: August 27, 2021
• Study Completion: August 27, 2021
• Last Updated: October 19, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)