Study of Human Plasma-Derived Alpha1-Proteinase Inhibitor in Subjects With New-Onset Type 1 Diabetes Mellitus
Condition: Type 1 Diabetes Mellitus
MeSH terms: Alpha 1-Antitrypsin Deficiency; Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: 180 mg/kg Alpha1-PI; 90 mg/kg Alpha1-PI; Placebo
Intervention MeSH terms: Protease Inhibitors; Alpha 1-Antitrypsin; Protein C Inhibitor
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 76.0
Sex: All
Minimum age: 6 Years
Maximum age: 35 Years
Healthy volunteers: No
Keywords: Type 1 Diabetes Mellitus; Alpha1-Proteinase Inhibitor; Beta Cell; Alpha1-Antitrypsin

Summary:

      This is a multicenter, randomized, partial-blinded, five-arm, placebo-controlled study of
      human plasma-derived alpha1-proteinase inhibitor (alpha1-PI) in children (ages 6-11 years
      old) and teens/adults (ages 12-35 years old) with new onset Type 1 Diabetes Mellitus (T1DM).
      Currently enrolling ages 12-35 only. Once 25 patients are randomized and data is reviewed
      enrollment will be opened to the child cohort. The purpose of this study is to evaluate the
      safety and efficacy of four dosing regimens of human plasma-derived alpha1-PI in T1DM.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of T1DM according to the ADA criteria.

          -  Current use of injected insulin therapy and one positive result on testing for any of
             the following antibodies (If not currently on insulin therapy, must have positive
             result for at least two of the below antibodies):

               -  Anti-islet-cell antibodies (islet cell antigen 512, insulinoma associated protein
                  2),

               -  Anti-glutamic acid decarboxylase antibodies, or

               -  Anti-insulin antibodies (unless received insulin therapy for > 7 days).

          -  Body Mass Index (BMI) ≤ 28 kg/m2 for adults (≥ 20 years of age) OR ≤ 90th percentile
             in accordance with the Centers for Disease Control BMI assessment for children and
             teens (2 through 19 years old).

        Exclusion Criteria:

          -  History of or current diabetic retinopathy, neuropathy, or nephropathy.

          -  Known thrombophilia or history of thrombosis.

          -  Malignant disease (including malignant melanoma; however, other forms of skin cancer
             are allowed) within five years of randomization.

          -  Active Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, or Human
             Immunodeficiency Virus infection.

          -  History of anaphylaxis or severe systemic response to any plasma-derived alpha1-PI
             preparation or other blood product(s).

          -  Known selective or severe Immunoglobulin A deficiency.

          -  Elevated liver enzymes (aspartate transaminase, alanine aminotransferase, and alkaline
             phosphatase) equal to or greater than 2.5 times the upper limit of normal.

          -  Therapy with exenatide or any other agents that stimulate pancreatic β cell
             regeneration or insulin secretion, or any antidiabetic agents (oral or parenteral)
             other than insulin within one month prior to screening.

          -  Use of omega-3 fatty acid supplements, including fish oil, within seven days prior to
             screening.

          -  Current or planned therapy with inhaled insulin, if it becomes available.

          -  Chronic use of systemic steroids, with the exception of inhaled steroids, above a
             stable dose equivalent to 5 mg/day prednisone (e.g., 10 mg every 2 days) within 4
             weeks prior to randomization. It is recommended to maintain the same dose throughout
             the study. (Note: Subjects with autoimmune conditions (i.e., asthma) necessitating
             treatment with systemic short-term corticosteroids and administered a rapid taper are
             eligible per protocol with the caveat that the tapering is complete or decreased to
             the minimum requirement (i.e., 5 mg/day) at least 1 week prior to the Baseline visit
             (when randomization occurs) to ensure the subject is stable. For longer term steroid
             usage, please consult the Grifols Medical Monitor before considering the subject for
             study participation.)

          -  Treatment with immunosuppressants or cytostatic agents within 6 months of
             randomization.