ATG-GCSF in New Onset Type 1 Diabetes
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Anti-Thymocyte Globulin (ATG); Granulocyte colony stimulating factor (GCSF); Placebo (for ATG); Placebo (for GCSF)
Intervention description: Thymoglobulin; Granulocyte colony stimulating factor (GCSF); Normal saline administered by IV infusion to mimic ATG; Placebo prepared to mimic 6mg subcutaneous injection of GCSF
Intervention MeSH terms: Lenograstim; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 89.0
Sex: All
Minimum age: 12 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: Type 1 Diabetes TrialNet

Summary:

      This is a three-arm, 1:1:1 randomized, placebo controlled, double- blinded trial in which at
      least 28 subjects will receive active Anti-Thymocyte Globulin and Granulocyte
      colony-stimulating factor (ATG-GCSF), at least 28 subjects will receive ATG alone and at
      least 28 subjects will receive placebo alone within 100 days from diagnosis of Type 1
      Diabetes (T1D).

      The primary objective of the study will be to determine the safety and ability of low dose
      ATG plus GCSF and low dose ATG alone to retain/enhance C-peptide production in new onset T1D
      patients demonstrating residual beta cell function.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must be > 12 years < 46

          -  Must have a diagnosis of T1D for less than 100 days at randomization

          -  Willing to provide Informed Consent or have a parent or legal guardian provide
             informed consent if the subject is <18 years of age

          -  Positive for at least one islet cell autoantibody; glutamic acid decarboxylase 65
             (GAD65A), Insulin micro IAA (mIAA), if obtained within 10 days of the onset of insulin
             therapy, islet antigen 2 (IA-2A), Islet Cell Antigen (ICA), or zinc transporter 8
             (ZnT8A)

          -  Must have stimulated C-peptide levels = 0.2 pmol/ml measured during a mixed meal
             tolerance test (MMTT) conducted at least 21 days from diagnosis of diabetes and within
             one month (37 days) of randomization

          -  Must be Epstein-Barr virus (EBV PCR) negative within two weeks of randomization if EBV
             seronegative at screening

          -  Be at least 6 weeks from last live immunization

          -  Participants are required to receive killed influenza vaccination at least 2 weeks
             prior to randomization when vaccine for the current or upcoming flu season is
             available

          -  Be willing to forgo vaccines during the treatment period and for 3 months following
             last dose of study drug

          -  Be willing to comply with intensive diabetes management

        Exclusion Criteria:

          -  Be immunodeficient or have clinically significant chronic lymphopenia: (Leukopenia (<
             3,000 leukocytes /µL), neutropenia (<1,500 neutrophils/µL), lymphopenia (<800
             lymphocytes/µL), or thrombocytopenia (<100,000 platelets/µL).

          -  Have active signs or symptoms of acute infection at the time of randomization

          -  Have evidence of prior or current tuberculosis infection as assessed by purified
             protein derivative (PPD), interferon gamma release assay (IGRA) or by history

          -  Be currently pregnant or lactating, or anticipate getting pregnant within the two year
             study period

          -  Require use of other immunosuppressive agents including chronic use of systemic
             steroids

          -  Have evidence of current or past human immunodeficiency virus (HIV), Hepatitis B or
             Hepatitis C infection

          -  Have any complicating medical issues or abnormal clinical laboratory results that may
             interfere with study conduct, or cause increased risk to include pre-existing cardiac
             disease, chronic obstructive pulmonary disease (COPD), sickle cell disease,
             neurological, or blood count abnormalities

          -  Have a history of malignancies other than skin

          -  Evidence of liver dysfunction with aspartate aminotransferase (AST) or alanine
             transaminase (ALT) greater than 3 times the upper limits of normal

          -  Evidence of renal dysfunction with creatinine greater than 1.5 times the upper limit
             of normal

          -  Vaccination with a live virus within the last 6 weeks

          -  Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control
             within prior 7 days of screening

          -  Active participation in another T1D treatment study in the previous 30 days

          -  Prior treatment with abatacept or anti-cd3

          -  Known allergy to GCSF or ATG

          -  Prior treatment with ATG or known allergy to rabbit derived products

          -  Any condition that in the investigator's opinion may adversely affect study
             participation or may compromise the study results