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

Phase 2

Terminated

Conditions: Type 1 Diabetes Mellitus

Interventions: Biological: Placebo
Biological: 90 mg/kg Alpha1-PI
Biological: 180 mg/kg Alpha1-PI

Registration Number: NCT02093221

Lead Sponsor: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 76

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo, 26 weeks	Placebo	Weekly infusions of placebo for 26 weeks.
90 mg/kg/wk Alpha1-PI, 26 weeks	90 mg/kg Alpha1-PI	90 mg/kg weekly infusions of Alpha1-PI for 26 weeks.
Placebo, 13 weeks	Placebo	Weekly infusions of placebo for 13 weeks.
Alpha1-PI 180 mg/kg/wk, 26 weeks	180 mg/kg Alpha1-PI	180 mg/kg weekly infusions of Alpha1-PI for 26 weeks.
90 mg/kg/wk Alpha1-PI, 13 weeks	90 mg/kg Alpha1-PI	90 mg/kg weekly infusions of Alpha1-PI for 13 weeks
180 mg/kg/wk Alpha1-PI, 13 weeks	180 mg/kg Alpha1-PI	180 mg/kg weekly infusions of Alpha1-PI for 13 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mixed Meal Tolerance Test (MMTMT) Stimulated C-peptide 2 Hour Area Under the Concentration-time Curve (AUC)	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

Name	Time	Method
Change From Baseline for MMTT Stimulated C-peptide 2h AUC	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	Baseline, Weeks 14, 27, 39, 52, 69, 87, and 104
Number of Subjects With Overall Severe Hypoglycemic Episodes	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	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	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.

Trial Locations

Locations (36): University of Texas Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
Children's Hospital of Pittsburgh
🇺🇸
Pittsburgh, Pennsylvania, United States
Endocrinology Associates Inc
🇺🇸
Columbus, Ohio, United States
Ohio State University
🇺🇸
Columbus, Ohio, United States
Advanced Pharma CR LLC
🇺🇸
Miami, Florida, United States
Methodist Research Institute
🇺🇸
Indianapolis, Indiana, United States
Clinica Medica San Miguel
🇺🇸
Los Angeles, California, United States
Diabetes Associates Medical Group
🇺🇸
Orange, California, United States
Rady Children's Hospital San Diego
🇺🇸
San Diego, California, United States
Metabolic Institute of America
🇺🇸
Tarzana, California, United States
Ronald H Chochinov MD
🇺🇸
Ventura, California, United States
Solutions Through Advanced Research Inc.
🇺🇸
Jacksonville, Florida, United States
Atlanta Diabetes Associates
🇺🇸
Atlanta, Georgia, United States
University of Iowa Hospitals and Clinics
🇺🇸
Iowa City, Iowa, United States
Cook County Hospital
🇺🇸
Chicago, Illinois, United States
WakeMed Children's Hospital
🇺🇸
Raleigh, North Carolina, United States
University of New Mexico, Health Sciences Center
🇺🇸
Albuquerque, New Mexico, United States
Women and Children's Hospital
🇺🇸
Buffalo, New York, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Research Institute of Dallas
🇺🇸
Dallas, Texas, United States
Children's Hospitals and Clinics of Minnesota
🇺🇸
Saint Paul, Minnesota, United States
Wayne State University
🇺🇸
Detroit, Michigan, United States
Pediatric Endocrinology, Genetics & Metabolism
🇺🇸
Oklahoma City, Oklahoma, United States
Northeast Clinical Research of San Antonio LLC
🇺🇸
San Antonio, Texas, United States
University of Texas Health Science Center
🇺🇸
San Antonio, Texas, United States
Consano Clinical Research
🇺🇸
San Antonio, Texas, United States
University of Louisville
🇺🇸
Louisville, Kentucky, United States
CCM Clinical Research
🇺🇸
Miami, Florida, United States
Rocky Mountain Diabetes and Osteoporosis Center
🇺🇸
Idaho Falls, Idaho, United States
Christiana Care Health Services
🇺🇸
Newark, Delaware, United States
Rapid City Regional Hospital/Health Clinical Research
🇺🇸
Rapid City, South Dakota, United States
UMass Memorial Medical Center
🇺🇸
Worcester, Massachusetts, United States
University of Arizona
🇺🇸
Tucson, Arizona, United States
Barry J. Reiner MD, LLC.
🇺🇸
Baltimore, Maryland, United States
Yale New Haven Hospital
🇺🇸
New Haven, Connecticut, United States
Morristown Medical Center
🇺🇸
Morristown, New Jersey, United States