ATG-GCSF in New Onset Type 1 Diabetes

• Status: Completed
• Trial end date: 2018-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: American Diabetes Association; Amgen; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Juvenile Diabetes Research Foundation; National Center for Research Resources (NCRR); National Institute of Allergy and Infectious Diseases (NIAID); Sanofi; The Leona M. and Harry B. Helmsley Charitable Trust
• Treatments: Antilymphocyte Serum; Lenograstim; Sargramostim; Thymoglobulin

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