T1DM Immunotherapy Using CD4+CD127lo/-CD25+ Polyclonal Tregs
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 1
Intervention: Ex vivo Expanded Human Autologous Polyclonal Regulatory T Cells
Intervention description: The researchers will multiply/expand the Tregs in the laboratory using anti-CD3/anti-CD28 coated beads plus IL-2. Then, the Tregs will be infused back into the patient in a single infusion. The first cohort will receive 0.05 x10^8 cells. The second cohort will receive 0.4 x10^8 cells. The third cohort will receive 3.2 x10^8 cells. The fourth cohort will receive 26 x10^8 cells.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: Diabetes; Treg

Summary:

      The investigational therapy under study in this trial, regulatory T cells (Tregs), offers the
      hope of stabilizing further destruction of insulin producing beta cells in type 1 diabetes.
      Tregs are a specialized subset of T cells that function to control the immune response.
      Pre-clinical studies in non-obese diabetic mice have demonstrated that adoptive transfer of
      Tregs can slow diabetes progression and, in some cases, reverse new onset diabetes. The
      primary purpose of this Phase 1 study is to assess the safety and feasibility of intravenous
      infusion of ex vivo selected and expanded autologous polyclonal Tregs in patients with type 1
      diabetes (T1DM) to support dose selection for a future efficacy trial. The study also aims to
      assess the effect of Tregs on beta cell function as well as on other measures of diabetes
      severity and the autoimmune response underlying T1DM.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of T1DM within >3 and <24 months of screening according to the American
             Diabetes Association criteria

          -  Between 18 and 45 years of age

          -  Positive test for Epstein-Barr antibody

          -  Positive test for at least one of the following antibodies:

               -  ICA512-antibody

               -  ICA

               -  GAD65-antibody

               -  Insulin (if assessed within 10 days of the onset of insulin therapy)

               -  ZnT8

          -  Peak C-peptide >0.1 pmol/ml (>0.3 ng/ml) during MMTT challenge

          -  Adequate venous access to support draw of 400 ml whole blood and infusion of
             investigational therapy

        Exclusion Criteria:

          -  Hemoglobin <10.0 g/dL; leukocytes <3,000/µL; neutrophils <1,500/µL; lymphocytes
             <800/µL; platelets <100,000/µL

          -  Regulatory T cells present in peripheral blood at <10 per µl as determined by flow
             cytometry

          -  Serologic evidence of HIV-1 or HIV-2 infection

          -  Evidence of current hepatitis B as demonstrated by HBsAg or circulating hepatitis B
             genomes

          -  Serologic evidence of hepatitis C infection

          -  Detectable circulating EBV or CMV genomes or active infection

          -  Positive PPD skin test defined as greater than or equal to 10 mm induration

          -  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 7.5mg 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

          -  Any chronic illness or prior treatment which in the opinion of the investigator should
             preclude participation in the trial

          -  Pregnant or breastfeeding women, any female who is unwilling to use a reliable and
             effective form of contraception for 2 years afer Treg dosing and any male who is
             unwilling to use a reliable and effective form of contraception for 3 months after
             Treg dosing.