A Research Trial of Aralast in New Onset Diabetes (RETAIN)
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Aralast NP 45 mg dose; Aralast NP 90 mg dose; Aralast NP 180 mg dose
Intervention description: - 45 mg/kg/week; - 90 mg/kg/week; - 180 mg/kg/week
Intervention MeSH terms: Alpha 1-Antitrypsin; Protein C Inhibitor
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 8 Years
Maximum age: 35 Years
Healthy volunteers: No
Keywords: Diabetes Mellitus, Type 1 (new-onset); Diabetes Mellitus, Insulin-Dependent (new-onset); new-onset T1DM; new-onset T1D; Diabetes Mellitus, Juvenile-Onset; Diabetes, Autoimmune; Aralast NP; Alpha-1 Antitrypsin; AAT

Summary:

      The drug Alpha-1 Antitrypsin (AAT, Aralast NP) is being tested in this study as an
      anti-inflammatory drug (a medication that decreases inflammation, which is part of the body's
      normal ability to fight infection and respond to injuries) that affects the cells thought to
      be involved in the development of type 1 diabetes mellitus (T1DM, T1D).

      All subjects enrolled in this study have new-onset T1DM (diagnosis of T1DM within 100 days of
      Visit 0; T1DM diagnosis fulfilling American Diabetes Association standard T1DM criteria). The
      focus of Part I of this trial (NCT01183468) is pharmacokinetics (PK), pharmacodynamics (PD)
      and safety. Upon completion of Part I, including a satisfactory safety review, enrollment in
      Part II (NCT01183455, Phase II Clinical Trial) will begin.
    

Eligibility criteria:

        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.