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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Grifols Therapeutics Inc.
Sponsor:
Information provided by (Responsible Party):
Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier:
NCT02093221
First received: March 11, 2014
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

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). 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 Intervention Phase
Type 1 Diabetes Mellitus
Biological: 180 mg/kg Alpha1-PI
Biological: 90 mg/kg Alpha1-PI
Biological: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Grifols Therapeutics Inc.:

Primary Outcome Measures:
  • C-peptide Area Under the concentration-time Curve (AUC) [ Time Frame: 10 min pre-dose, immediately pre-dose, 15, 30, 60, 90, and 120 minutes post-dose ] [ Designated as safety issue: No ]
    C-peptide concentration during mixed meal tolerance test with high protein energy drink. "Dose" for timeframe referes to intake of high protein energy drink.


Secondary Outcome Measures:
  • Number of subjects who discontinue due to Adverse Events (AEs) [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline for HbA1c levels [ Time Frame: Weeks 1 (Baseline), 14, 27, 39, 52, 69, 87, and 104 ] [ Designated as safety issue: No ]
  • Number of severe hypoglycemic episodes [ Time Frame: 104 weeks ] [ Designated as safety issue: No ]
    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.

  • Serum alpha1-PI AUC [ Time Frame: Immediately prior to last infusion, immediately after, 15 and 30 minutes after, and 1, 3, 8, 24, 48, 120, 168, 240, 336, 408, and 504 hours after last investigation product infusion ] [ Designated as safety issue: No ]
  • Mean trough serum alpha1-PI [ Time Frame: Immediately prior to the Week 12 and 13 or Week 25 and 26 investigational product infusions ] [ Designated as safety issue: No ]
    Blood samples for determination of trough total serum alpha1-PI concentration will be drawn prior to the Week 12 and 13 infusions or the Week 25 and 26 infusions depending on the randomized treatment group.


Estimated Enrollment: 75
Study Start Date: March 2014
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   6 Years to 35 Years
Genders Eligible for Study:   Both
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) ≤ 25 kg/m2 for adults (≥ 20 years of age) OR < 85th 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 three months 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.
  • Use of systemic steroids above a stable dose equivalent to 5 mg/day prednisone (e.g., 10 mg every 2 days) within the 4 weeks prior to randomization. It is recommended to maintain the same dose throughout the study.
  • Treatment with immunosuppressants or cytostatic agents within 6 months of randomization.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02093221

Contacts
Contact: Ed Corsi Ed.Corsi@grifols.com

  Show 27 Study Locations
Sponsors and Collaborators
Grifols Therapeutics Inc.
  More Information

No publications provided

Responsible Party: Grifols Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT02093221     History of Changes
Other Study ID Numbers: GTI1302
Study First Received: March 11, 2014
Last Updated: July 10, 2014
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on July 22, 2014