Imatinib Treatment in Recent Onset Type 1 Diabetes Mellitus

Inclusion Criteria:

• Males and females age 12-35 years of age who meet the ADA standard T1DM criteria1. Positive for at least one islet cell autoantibody.
• Diagnosis of T1DM within 100 days of Visit 0.
• Peak stimulated C-peptide level >0.2 pmol/mL following an MMTT.
• Participants of childbearing age who are sexually active must agree to use an effective form of birth control (e.g., barrier method, oral contraception, or surgery). For females, these contraceptive measures must be maintained throughout the study; for males these measures must be followed for a minimum of 3 months after discontinuation of imatinib therapy.

Exclusion Criteria:

• Prior history of any significant cardiac disease such as congestive heart failure, myocardial infarction, arrhythmia, or structural defects or suspicion thereof.
• Leukopenia (<3,000 leukocytes/µL), neutropenia (<1,500 neutrophils/µL), or thrombocytopenia (<125,000 platelets/µL).
• Low Hemoglobin
• 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). Significant acute infections must be resolved before treatment may commence, e.g., acute respiratory tract, urinary tract, or gastrointestinal tract infections.
• 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, or amylin.
• Prior or current treatment that is known to cause a significant, ongoing change in the course of T1DM or immunologic status, including high-dose inhaled, extensive topical or systemic glucocorticoids.
• Evidence of liver dysfunction, with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.0 times the upper limit of normal persistent for 1 week or greater.
• Evidence of renal insufficiency as indicated by serum creatinine of >1.2 times the upper limit of normal confirmed in a repeat test at least 1 week apart.
• Evidence of clinically significant metabolic bone disease (except adequately treated rickets).
• Females who are pregnant at the time of screening or unwilling to defer pregnancy during the 24-month study period.
• Prior treatment with imatinib or related tyrosine kinase inhibitor.
• Unable to avoid medications that affect CYP3A4: either inducers that may decrease imatinib levels, or inhibitors that may increase drug concentrations. (Refer to section 1.5.1.12 for a complete list of inducers and inhibitors.)
• Height standard deviation score ≥2 standard deviations below mean
• Any sign of QT prolongation on Visit 0 and Visit 1 ECG
• Known coagulation disorders or use of anticoagulants
• Any condition that, in the investigator's opinion, may compromise study participation or may confound the interpretation of the study results.