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

Researchers are interested in conducting this study to assess whether Aralast NP (AAT,
Alpha-1 Antitrypsin ) will help slow the progression of T1DM.

Part I of this study has two parts:-1a and -1b:

Part 1a (Complete): An open-label, dose-escalation, PK, PD and safety study. Participants
receive 12 intravenous (IV) infusions of Aralast NP. Infusions 1 through 6 are administered
at 45 mg/kg/wk and infusions 7 through 12 are administered at 90 mg/kg/wk.

Part Ia consists of two groups:

- Subjects aged 16 - 35 years at enrollment with new-onset T1DM

- Subjects aged 8 -15 years at enrollment with new-onset T1DM.

Part 1b (study terminated prior to subject enrollment): An open-label, dose-escalation PK, PD
and safety study in which participants receive 12 infusions of Aralast NP. Infusions 1
through 6 are administered at 90 mg/kg/wk and infusions 7 through 12 are administered at 180
mg/kg/wk. Part Ib consists of two groups:

- Subjects aged 16 - 35 years at enrollment with new-onset T1DM

- Subjects 8 - 15 years at enrollment with new-onset T1DM.

Participants in Part Ib do not roll over into Part II (Refer to NCT01183455).

Inclusion Criteria:

- Diagnosed with T1DM within the past 100 days (of enrollment)

- 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:

- Severe active disease (chronic active hepatitis; cardiac, pulmonary disease, hepatic,
renal or immunodeficiency)

- History of any bleeding or clotting factor deficiencies, or stroke

- History of vascular disease or significant vascular abnormalities

- Positive serology of exposure to (hepatitis B virus) HBV, HCV (hepatitis C virus), HIV
(human immunodeficiency virus) or toxoplasmosis

- Clinically active infection with EBV (Epstein-Barr virus), CMV (cytomegalovirus), or
tuberculosis(TB)

- 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 Alpha 1-Antitrypsin (Aralast NP, AAT) or hypersensitivity to
alpha 1-antitrypsin 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 (immunoglobulin A) 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.