The Effects of Alpha-1 Antitrypsin (AAT) on the Progression of Type 1 Diabetes

The Effects of Open Label Alpha-1 Antitrypsin on the Progression of Type 1 Diabetes in Subjects With Detectable C-peptide

The purpose of this study is to determine if the drug Alpha-1 Antitrypsin (AAT, Aralast NP) will preserve beta-cell function and help slow the progression of type 1 diabetes.

Inclusion Criteria:

• Diagnosis of Type 1 Diabetes Mellitus based on ADA Criteria for fewer than 5 years but more than 100 days
• 6-45 years of age, inclusive. To assess safety, we will initially enroll 8 patients over the age of 16. Following the last infusion of the 8th patient, we will assess adverse events. As long as there are no stopping criteria met for these 8 patients we will decrease the age criteria down to 6 years old.
• C-peptide increase during screening mixed meal tolerance test with a minimal stimulated value of ≥ 0.2 pmol/mL.
• Positive for antibodies to insulin (if insulin autoantibody positive only, determination must be within two weeks of insulin initiation), GAD-65, IA-2 or ZnT8
• Agree to intensive management of diabetes with an HgbA1c goal of < 7.0%
• If female, (a) surgically sterile or (b) postmenopausal or (c) if of reproductive potential, willing to use medically acceptable birth control (e.g. female hormonal contraception, barrier methods or sterilization. ) until 3 months after completion of any treatment period
• If male and of reproductive potential, willing to use medically acceptable birth control until 3 months after completion of any treatment period, unless the female partner is postmenopausal or surgically sterile
• Serum creatinine ≤ 1.5 x upper limit of normal
• AST < 2 times the upper limit of normal
• Hematology:WBC > 3000 x 109/L; platelets > 100 x 109/L; hemoglobin > 10.0 g/dL.

Exclusion Criteria:

• Unable or unwilling to comply with the requirements of the study protocol
• Body Mass Index (BMI) > 30 kg/m2
• Unstable blood sugar control defined as one or more episodes of severe hypoglycemia (defined as hypoglycemia that required the assistance of another person) within the last 30 days
• Previous immunotherapy for T1D
• Administration of an experimental agent for T1D at any time or use of an experimental device for T1D within 30 days of screening, unless approved by the study PI
• History of any organ transplant, including islet cell transplant
• Active autoimmune or immune deficiency disorder (e.g. sarcoidosis, rheumatoid arthritis)
• Serum bilirubin > ULN, except those subjects whose abnormal values were attributed to any stable, benign condition (such as Gilbert's Syndrome) may be included
• TSH outside the normal range at screening, except those subjects on stable doses of thyroid hormone replacement therapy may be included
• Known HIV positivity, active hepatitis B or active hepatitis C infection
• Anticipated pregnancy during active dosing or within 3 months after completion of active dosing phase
• History of a malignant neoplasm within the previous 5 years (except in situ cervical cancer and curable non-melanoma skin malignancy)
• Any social condition or medical condition that would, in the opinion of the investigator, prevent complete participation in the study or that would pose a significant hazard to the subjects' participation
• History of active substance abuse within 12 months of screening
• A psychiatric or medical disorder that would prevent giving informed consent
• Individuals with a history of IgA deficiency
• Individuals with a history of hypersensitivity to AAT