A Research Trial of Aralast in New Onset Diabetes (RETAIN) - Part I

• MMTT-stimulated peak and 4-hour C-peptide AUC [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
• MMTT-stimulated 2-hour C-peptide AUC assessed longitudinally [ Time Frame: Weeks 0, 14, 26, 52, and 104 ] [ Designated as safety issue: No ]
• Insulin use in units per kilogram body weight per day [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
  Insulin use in units per kilogram body weight per day
• Hypoglycemic events occurring from randomization [ Time Frame: Throughout the trial ] [ Designated as safety issue: Yes ]
• Glycosylated hemoglobin (HbA1C) levels [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
• Emergence of anti-AAT antibodies [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
• Frequency and severity of all AEs (including infusion reactions, hypersensitivity reactions, and viral infections) [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
• Changes in D-dimer levels indicating alteration in coagulant/anticoagulant balance [ Time Frame: Throughout the trial ] [ Designated as safety issue: Yes ]
• Pharmacokinetic parameters of Aralast NP [ Time Frame: Throughout the trial ] [ Designated as safety issue: No ]

The drug Alpha-1 Antitrypsin (AAT, Aralast NP), which is being tested in this clinical trial,is an anti-inflammatory drug that affects the cells that are thought to be involved in the development of type 1 diabetes. This trial, known as RETAIN, is a two-part trial to investigate the effect of intravenous Alpha-1 Antitrypsin(AAT, Aralast NP) on preserving beta cell function and to determine if AAT will help slow the progression of type 1 diabetes.

Part I of this clinical trial is an open-label, safety and dose level study consisting of two groups. In Part I, all participants will receive the experimental drug and will be tested to see if the drug is safe and well tolerated. Two groups of participants with new-onset type 1 diabetes will be enrolled. After participants have completed the trial and a satisfactory safety review is completed, enrollment in Part II of the study will begin.

Type 1 diabetes mellitus is an autoimmune disease. This means that your immune system (the part of your body that helps fight infections) mistakenly attacks the cells that produce insulin (beta cells in the pancreas). As beta cells are destroyed by your immune cells, your ability to produce insulin is decreased. Insulin helps keep blood glucose levels normal.

People with type 1 diabetes who have the ability to produce some of their own insulin (even though they still need to take insulin) may be able to achieve better glucose control than people who produce no insulin at all. Better glucose control has been shown to reduce the long-term complications of diabetes. Previous research has shown that giving medicines to affect the immune system soon after type 1 diabetes is diagnosed may stop, delay or decrease the destruction of beta cells, resulting in better glucose control.

In mouse models of disease, Alpha-1 Antitrypsin (AAT, Aralast NP) has been shown to reverse new-onset diabetes and induce a state of self-tolerance. The RETAIN study is a two-part trial investigating the effect of intravenous Alpha-1 antitrypsin(AAT, Aralast NP) on preserving beta cell function and whether AAT will help slow the progression of type 1 diabetes.

Inclusion Criteria:

• Diagnosed with type 1 diabetes within the past 100 days
• Positive for at least one diabetes-related autoantibody (Anti-GAD; Anti-insulin, if obtained within 10 days of the onset of insulin therapy; IA-2 antibody and/or ICA, or ZnT8.)
• Peak stimulated C-peptide level > 0.2 pmol/mL following a mixed meal tolerance test (MMTT)

Exclusion Criteria:

• Serve active disease (hepatitis, cardiac or pulmonary disease, hypertension, immunodeficiency)
• History of any bleeding or clotting factor deficiencies, or stroke
• History of vascular disease or significant vascular abnormalities
• Positive serology exposure to HBV, HCV, HIV or toxoplasmosis
• Clinically active infection with EBV, CMV, or tuberculosis
• Prior or current use of oral, inhaled or intranasal glucocorticoids, or any medication known to cause a significant, ongoing change in the course of T1DM or immunologic status
• Prior treatment with AAT or hypersensitivity to AAT or human plasma-derived products
• Current or prior (within the last 30 days) use of metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors or amylin.
• Current use of any medication known to influence glucose tolerance (e.g., beta-blockers, angiotensin-converting enzyme inhibitors, interferons, quinidine anti-malarial drugs, lithium, niacin)
• Females who are pregnant or lactating, or are unwilling to defer pregnancy during study participation.
• IgA deficiency
• Uncontrolled hypertension.
• Current life-threatening malignancy.
• Any condition that in the investigator's opinion may compromise study participation or may confound the interpretation of the study results.

• Immune Tolerance Network (ITN)
• Juvenile Diabetes Research Foundation