Clinical trial NCT02093221: Study of Human Plasma-Derived Alpha1-Proteinase Inhibitor in Subjects With New-Onset Type 1 Diabetes Mellitus
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Type 1 Diabetes Mellitus
Keywords: Type 1 Diabetes Mellitus
Alpha1-Proteinase Inhibitor
Beta Cell
Alpha1-Antitrypsin
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2014-03-20
Enrollment: 76
Sex: ALL
Minimum age (years): 6
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change From Baseline in Mixed Meal Tolerance Test (MMTMT) Stimulated C-peptide 2 Hour Area Under the Concentration-time Curve (AUC)
timeFrame: Baseline, Week 52 (pre-high protein drink and 15, 30, 60, 90, 120 minutes post-drink)
Secondary outcomes:
measure: Change From Baseline for MMTT Stimulated C-peptide 2h AUC
timeFrame: Baseline, Weeks 14, 27, 39, 69, 87, and 104 (pre-high protein drink and 15, 30, 60, 90, 120 minutes post-drink)
measure: Change From Baseline for HbA1c Levels
timeFrame: Baseline, Weeks 14, 27, 39, 52, 69, 87, and 104
measure: Number of Subjects With Overall Severe Hypoglycemic Episodes
timeFrame: 104 weeks
measure: Change From Baseline for Mean Daily Insulin Dose Requirements
timeFrame: Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104
measure: Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime
timeFrame: Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Los Angeles
country: United States
facility: Clinica Medica San Miguel
state: California
city: Orange
country: United States
facility: Diabetes Associates Medical Group
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital San Diego
state: California
city: Tarzana
country: United States
facility: Metabolic Institute of America
state: California
city: Ventura
country: United States
facility: Ronald H Chochinov MD
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Newark
country: United States
facility: Christiana Care Health Services
state: Delaware
city: Jacksonville
country: United States
facility: Solutions Through Advanced Research Inc.
state: Florida
city: Miami
country: United States
facility: CCM Clinical Research
state: Florida
city: Miami
country: United States
facility: Advanced Pharma CR LLC
state: Florida
city: Atlanta
country: United States
facility: Atlanta Diabetes Associates
state: Georgia
city: Idaho Falls
country: United States
facility: Rocky Mountain Diabetes and Osteoporosis Center
state: Idaho
city: Chicago
country: United States
facility: Cook County Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Methodist Research Institute
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Baltimore
country: United States
facility: Barry J. Reiner MD, LLC.
state: Maryland
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Saint Paul
country: United States
facility: Children's Hospitals and Clinics of Minnesota
state: Minnesota
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico, Health Sciences Center
state: New Mexico
city: Buffalo
country: United States
facility: Women and Children's Hospital
state: New York
city: Raleigh
country: United States
facility: WakeMed Children's Hospital
state: North Carolina
city: Columbus
country: United States
facility: Endocrinology Associates Inc
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: Pediatric Endocrinology, Genetics & Metabolism
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Rapid City
country: United States
facility: Rapid City Regional Hospital/Health Clinical Research
state: South Dakota
city: Dallas
country: United States
facility: Research Institute of Dallas
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: San Antonio
country: United States
facility: Northeast Clinical Research of San Antonio LLC
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center
state: Texas
city: San Antonio
country: United States
facility: Consano Clinical Research
state: Texas
Study officials:
References:
citation: Lagarde WH, Courtney KL, Reiner B, Steinmann K, Tsalikian E, Willi SM. Human plasma-derived alpha1 -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.