Study Stopped
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.
Study of Human Plasma-Derived Alpha1-Proteinase Inhibitor in Subjects With New-Onset Type 1 Diabetes Mellitus
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
1 other identifier
interventional
76
1 country
36
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Mar 2014
Typical duration for phase_2
36 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2014
CompletedFirst Submitted
Initial submission to the registry
March 11, 2014
CompletedFirst Posted
Study publicly available on registry
March 20, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2017
CompletedResults Posted
Study results publicly available
April 19, 2018
CompletedSeptember 5, 2018
August 1, 2018
2.8 years
March 11, 2014
March 23, 2018
August 6, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline in Mixed Meal Tolerance Test (MMTMT) Stimulated C-peptide 2 Hour Area Under the Concentration-time Curve (AUC)
C-peptide concentration during MMTT with high protein energy drink. "Dose" for time frame refers to intake of high protein energy drink.
Baseline, Week 52 (pre-high protein drink and 15, 30, 60, 90, 120 minutes post-drink)
Secondary Outcomes (5)
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
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
Study Arms (6)
Alpha1-PI 180 mg/kg/wk, 26 weeks
EXPERIMENTAL180 mg/kg weekly infusions of Alpha1-PI for 26 weeks.
90 mg/kg/wk Alpha1-PI, 26 weeks
EXPERIMENTAL90 mg/kg weekly infusions of Alpha1-PI for 26 weeks.
Placebo, 26 weeks
PLACEBO COMPARATORWeekly infusions of placebo for 26 weeks.
180 mg/kg/wk Alpha1-PI, 13 weeks
EXPERIMENTAL180 mg/kg weekly infusions of Alpha1-PI for 13 weeks.
90 mg/kg/wk Alpha1-PI, 13 weeks
EXPERIMENTAL90 mg/kg weekly infusions of Alpha1-PI for 13 weeks
Placebo, 13 weeks
PLACEBO COMPARATORWeekly infusions of placebo for 13 weeks.
Interventions
Eligibility Criteria
You may qualify if:
- 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).
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (36)
University of Arizona
Tucson, Arizona, 85724, United States
Clinica Medica San Miguel
Los Angeles, California, 90015, United States
Diabetes Associates Medical Group
Orange, California, 92868, United States
Rady Children's Hospital San Diego
San Diego, California, 92123, United States
Metabolic Institute of America
Tarzana, California, 91356, United States
Ronald H Chochinov MD
Ventura, California, 93003, United States
Yale New Haven Hospital
New Haven, Connecticut, 06511, United States
Christiana Care Health Services
Newark, Delaware, 19713, United States
Solutions Through Advanced Research Inc.
Jacksonville, Florida, 32258, United States
CCM Clinical Research
Miami, Florida, 33133, United States
Advanced Pharma CR LLC
Miami, Florida, 33136, United States
Atlanta Diabetes Associates
Atlanta, Georgia, 30309, United States
Rocky Mountain Diabetes and Osteoporosis Center
Idaho Falls, Idaho, 83404, United States
Cook County Hospital
Chicago, Illinois, 60612, United States
Methodist Research Institute
Indianapolis, Indiana, 46202, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242, United States
University of Louisville
Louisville, Kentucky, 40202, United States
Barry J. Reiner MD, LLC.
Baltimore, Maryland, 21229, United States
UMass Memorial Medical Center
Worcester, Massachusetts, 01655, United States
Wayne State University
Detroit, Michigan, 48201, United States
Children's Hospitals and Clinics of Minnesota
Saint Paul, Minnesota, 55102, United States
Morristown Medical Center
Morristown, New Jersey, 07962, United States
University of New Mexico, Health Sciences Center
Albuquerque, New Mexico, 87131-0001, United States
Women and Children's Hospital
Buffalo, New York, 14222, United States
WakeMed Children's Hospital
Raleigh, North Carolina, 27610, United States
Endocrinology Associates Inc
Columbus, Ohio, 43201, United States
Ohio State University
Columbus, Ohio, 43210, United States
Pediatric Endocrinology, Genetics & Metabolism
Oklahoma City, Oklahoma, 73112, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19106, United States
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224, United States
Rapid City Regional Hospital/Health Clinical Research
Rapid City, South Dakota, 57701, United States
Research Institute of Dallas
Dallas, Texas, 75231, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
Northeast Clinical Research of San Antonio LLC
San Antonio, Texas, 78154, United States
University of Texas Health Science Center
San Antonio, Texas, 78229, United States
Consano Clinical Research
San Antonio, Texas, 78232, United States
Related Publications (1)
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.
PMID: 33244872DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Kimberly Steinmann, MD
- Organization
- Grifols Therapeutics LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 11, 2014
First Posted
March 20, 2014
Study Start
March 1, 2014
Primary Completion
January 1, 2017
Study Completion
June 1, 2017
Last Updated
September 5, 2018
Results First Posted
April 19, 2018
Record last verified: 2018-08