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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE March 11, 2014
First Posted Date  ICMJE March 20, 2014
Results First Submitted Date  ICMJE March 23, 2018
Results First Posted Date  ICMJE April 19, 2018
Last Update Posted Date September 5, 2018
Study Start Date  ICMJE March 2014
Actual Primary Completion Date January 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 6, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 18, 2014)
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 ]
C-peptide concentration during mixed meal tolerance test with high protein energy drink. "Dose" for timeframe referes to intake of high protein energy drink.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 6, 2018)
  • 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) ]
  • Change From Baseline for HbA1c Levels [ Time Frame: Baseline, Weeks 14, 27, 39, 52, 69, 87, and 104 ]
  • 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.
  • Change From Baseline for Mean Daily Insulin Dose Requirements [ Time Frame: Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104 ]
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2014)
  • Number of subjects who discontinue due to Adverse Events (AEs) [ Time Frame: 52 weeks ]
  • Change from baseline for HbA1c levels [ Time Frame: Weeks 1 (Baseline), 14, 27, 39, 52, 69, 87, and 104 ]
  • Number of 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.
  • 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 ]
  • Mean trough serum alpha1-PI [ Time Frame: Immediately prior to the Week 12 and 13 or Week 25 and 26 investigational product infusions ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Human Plasma-Derived Alpha1-Proteinase Inhibitor in Subjects With New-Onset Type 1 Diabetes Mellitus
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Type 1 Diabetes Mellitus
Intervention  ICMJE
  • Biological: 180 mg/kg Alpha1-PI
    Other Names:
    • Alpha1-antitrypsin
    • Prolastin-C
    • Alpha1-Proteinase Inhibitor (human), Modified Process
    • Alpha-1 MP
  • Biological: 90 mg/kg Alpha1-PI
    Other Names:
    • Alpha1-antitrypsin
    • Prolastin-C
    • Alpha1-Proteinase Inhibitor (human), Modified Process
    • Alpha-1 MP
  • Biological: Placebo
Study Arms  ICMJE
  • Experimental: Alpha1-PI 180 mg/kg/wk, 26 weeks
    180 mg/kg weekly infusions of Alpha1-PI for 26 weeks.
    Intervention: Biological: 180 mg/kg Alpha1-PI
  • Experimental: 90 mg/kg/wk Alpha1-PI, 26 weeks
    90 mg/kg weekly infusions of Alpha1-PI for 26 weeks.
    Intervention: Biological: 90 mg/kg Alpha1-PI
  • Placebo Comparator: Placebo, 26 weeks
    Weekly infusions of placebo for 26 weeks.
    Intervention: Biological: Placebo
  • Experimental: 180 mg/kg/wk Alpha1-PI, 13 weeks
    180 mg/kg weekly infusions of Alpha1-PI for 13 weeks.
    Intervention: Biological: 180 mg/kg Alpha1-PI
  • Experimental: 90 mg/kg/wk Alpha1-PI, 13 weeks
    90 mg/kg weekly infusions of Alpha1-PI for 13 weeks
    Intervention: Biological: 90 mg/kg Alpha1-PI
  • Placebo Comparator: Placebo, 13 weeks
    Weekly infusions of placebo for 13 weeks.
    Intervention: Biological: Placebo
Publications * Lagarde WH, Courtney KL, Reiner B, Steinmann K, Tsalikian E, Willi SM. Human plasma-derived alpha(1) -proteinase inhibitor in patients with new-onset type 1 diabetes mellitus: A randomized, placebo-controlled proof-of-concept study. Pediatr Diabetes. 2021 Mar;22(2):192-201. doi: 10.1111/pedi.13162. Epub 2020 Dec 13.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 10, 2016)
76
Original Estimated Enrollment  ICMJE
 (submitted: March 18, 2014)
75
Actual Study Completion Date  ICMJE June 2017
Actual Primary Completion Date January 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 35 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02093221
Other Study ID Numbers  ICMJE GTI1302
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Grifols Therapeutics LLC
Study Sponsor  ICMJE Grifols Therapeutics LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Grifols Therapeutics LLC
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP