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

Type 1 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02093221
• Other study ID #: GTI1302
• Status: Terminated
• Phase: Phase 2
• Start date: March 2014
• Est. completion date: June 2017

Study information

• Verified date: August 2018
• Source: Grifols Therapeutics LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 76
• Est. completion date: June 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 35 Years

Eligibility

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 ß 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.

Related Conditions & MeSH terms

• Alpha 1-Antitrypsin Deficiency
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Biological:
• 180 mg/kg Alpha1-PI

• 90 mg/kg Alpha1-PI

• Placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Grifols Therapeutics LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	Change From Baseline for HbA1c Levels		Baseline, Weeks 14, 27, 39, 52, 69, 87, and 104
Secondary	Number of Subjects With Overall Severe Hypoglycemic Episodes	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.	104 weeks
Secondary	Change From Baseline for Mean Daily Insulin Dose Requirements		Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104
Secondary	Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime	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.	Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104