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.
A Phase 1 Trial of CD4+CD127lo/-CD25+ Polyclonal Treg Adoptive Immunotherapy With Interleukin-2 for the Treatment of Type 1 Diabetes
The investigators hypothesize that ex vivo expanded human autologous CD4+CD127lo/-CD25+ polyclonal regulatory T cells (Polyclonal Tregs) plus Interleukin-2 (IL-2) administered to patients with Type 1 Diabetes Mellitus (T1DM) will be safe and biologically active. A Phase I trial with this cellular therapy plus IL-2 will lead the way for Phase II trials that test for efficacy based on preservation of C-peptide, reduced exogenous insulin requirements and improved glycemic control.
This is a Phase I safety/dosing study of Polyclonal Tregs + IL-2 in patients with T1DM.
The Tregs will be expanded using an established protocol utilizing anti-CD3/anti-CD28 beads plus IL-2. The study will involve 2 dosing cohorts of 6-8 T1DM patients each. The primary objective 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. The study will also assess potential effects of Tregs on beta cell function and the autoimmune response.
Subjects will receive Polyclonal Tregs at doses of 3 or 20x106 cells/kg. The dose of Tregs is selected based on a combination of considerations of manufacturing capacity, a predicted efficacious dose, and the available safety data of the Treg product currently in clinical trials. The IL-2 dose will be 1 x106 IU subcutaneously, given daily for 5 consecutive days at the completion of the cell infusion and again after 1 month. This dose is based on recent studies from Klatzmann et al. in T1DM, where the dose was found to be effective in a selective Treg expansion, well tolerated, and without an acute decline in beta cell function (Rosenzwajg et al., 2015).
Type 1 Diabetes Mellitus Diabetes Treg Proluekin
You can join if…
Open to people ages 18–45
- Diagnosis of T1DM within >3 and <24 months of day 0 according to the American Diabetes Association standard criteria.
- 18 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
- 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 CAN'T join 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,CMV, or toxoplasmosis), 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.
- University of California, San Francisco Medical Center accepting new patients
San Francisco, California, 94143, United States
- Yale University accepting new patients
New Haven, Connecticut, 06519, United States
Please contact me about this study
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If you do not hear from the study team, please call 888-689-8273 and tell them you’re interested in study number NCT02772679.