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Study of Human Plasma-Derived Alpha1-Proteinase Inhibitor in Subjects With New-Onset Type 1 Diabetes Mellitus

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ClinicalTrials.gov Identifier: NCT02093221
Recruitment Status : Terminated (Wk 52 primary endpoint results would be unaffected by follow-up data so trial was discontinued prior to wk 104. No safety data was collected after wk 52.)
First Posted : March 20, 2014
Results First Posted : April 19, 2018
Last Update Posted : September 5, 2018
Sponsor:
Information provided by (Responsible Party):
Grifols Therapeutics LLC

Brief 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.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Biological: 180 mg/kg Alpha1-PI Biological: 90 mg/kg Alpha1-PI Biological: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Partial-Blinded, Placebo-Controlled Study to Evaluate the Safety and Efficacy of a Human Plasma-Derived Alpha1-Proteinase Inhibitor in Subjects With New-Onset Type 1 Diabetes Mellitus
Study Start Date : March 2014
Actual Primary Completion Date : January 2017
Actual Study Completion Date : June 2017


Arm Intervention/treatment
Experimental: Alpha1-PI 180 mg/kg/wk, 26 weeks
180 mg/kg weekly infusions of Alpha1-PI for 26 weeks.
Biological: 180 mg/kg Alpha1-PI
Other Names:
  • Alpha1-antitrypsin
  • Prolastin-C
  • Alpha1-Proteinase Inhibitor (human), Modified Process
  • Alpha-1 MP

Experimental: 90 mg/kg/wk Alpha1-PI, 26 weeks
90 mg/kg weekly infusions of Alpha1-PI for 26 weeks.
Biological: 90 mg/kg Alpha1-PI
Other Names:
  • Alpha1-antitrypsin
  • Prolastin-C
  • Alpha1-Proteinase Inhibitor (human), Modified Process
  • Alpha-1 MP

Placebo Comparator: Placebo, 26 weeks
Weekly infusions of placebo for 26 weeks.
Biological: Placebo
Experimental: 180 mg/kg/wk Alpha1-PI, 13 weeks
180 mg/kg weekly infusions of Alpha1-PI for 13 weeks.
Biological: 180 mg/kg Alpha1-PI
Other Names:
  • Alpha1-antitrypsin
  • Prolastin-C
  • Alpha1-Proteinase Inhibitor (human), Modified Process
  • Alpha-1 MP

Experimental: 90 mg/kg/wk Alpha1-PI, 13 weeks
90 mg/kg weekly infusions of Alpha1-PI for 13 weeks
Biological: 90 mg/kg Alpha1-PI
Other Names:
  • Alpha1-antitrypsin
  • Prolastin-C
  • Alpha1-Proteinase Inhibitor (human), Modified Process
  • Alpha-1 MP

Placebo Comparator: Placebo, 13 weeks
Weekly infusions of placebo for 13 weeks.
Biological: Placebo



Primary Outcome Measures :
  1. Change From Baseline in Mixed Meal Tolerance Test (MMTMT) Stimulated C-peptide 2 Hour Area Under the Concentration-time Curve (AUC) [ Time Frame: Baseline, Week 52 (pre-high protein drink and 15, 30, 60, 90, 120 minutes post-drink) ]
    C-peptide concentration during MMTT with high protein energy drink. "Dose" for time frame refers to intake of high protein energy drink.


Secondary Outcome Measures :
  1. Change From Baseline for MMTT Stimulated C-peptide 2h AUC [ Time Frame: Baseline, Weeks 14, 27, 39, 69, 87, and 104 (pre-high protein drink and 15, 30, 60, 90, 120 minutes post-drink) ]
  2. Change From Baseline for HbA1c Levels [ Time Frame: Baseline, Weeks 14, 27, 39, 52, 69, 87, and 104 ]
  3. Number of Subjects With Overall Severe Hypoglycemic Episodes [ Time Frame: 104 weeks ]
    Severe hypoglycemia defined according the ADA Workgroup on Hypoglycemia definition, as follows: An event requiring assistance of another person to actively administer carbohydrate, glucagons, or other resuscitative actions.

  4. Change From Baseline for Mean Daily Insulin Dose Requirements [ Time Frame: Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104 ]
  5. Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime [ Time Frame: Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104 ]
    For each visit, the mean daily glucose levels were calculated over the previous 3-7 days prior to the study visit from blood glucose levels recorded daily prior to meals and bedtime.



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Ages Eligible for Study:   6 Years to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02093221


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Sponsors and Collaborators
Grifols Therapeutics LLC

Responsible Party: Grifols Therapeutics LLC
ClinicalTrials.gov Identifier: NCT02093221     History of Changes
Other Study ID Numbers: GTI1302
First Posted: March 20, 2014    Key Record Dates
Results First Posted: April 19, 2018
Last Update Posted: September 5, 2018
Last Verified: August 2018

Keywords provided by Grifols Therapeutics LLC:
Type 1 Diabetes Mellitus
Alpha1-Proteinase Inhibitor
Beta Cell
Alpha1-Antitrypsin

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Alpha 1-Antitrypsin Deficiency
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Liver Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema
Emphysema
Pathologic Processes
Alpha 1-Antitrypsin
Protein C Inhibitor
Protease Inhibitors
Trypsin Inhibitors
Serine Proteinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action