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

NCT ID: NCT02093221

Last Updated: 2018-09-05

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

76 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-31

Study Completion Date

2017-06-30

Brief Summary

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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

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Conditions

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Type 1 Diabetes Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Alpha1-PI 180 mg/kg/wk, 26 weeks

180 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

Group Type EXPERIMENTAL

180 mg/kg Alpha1-PI

Intervention Type BIOLOGICAL

90 mg/kg/wk Alpha1-PI, 26 weeks

90 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

Group Type EXPERIMENTAL

90 mg/kg Alpha1-PI

Intervention Type BIOLOGICAL

Placebo, 26 weeks

Weekly infusions of placebo for 26 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

180 mg/kg/wk Alpha1-PI, 13 weeks

180 mg/kg weekly infusions of Alpha1-PI for 13 weeks.

Group Type EXPERIMENTAL

180 mg/kg Alpha1-PI

Intervention Type BIOLOGICAL

90 mg/kg/wk Alpha1-PI, 13 weeks

90 mg/kg weekly infusions of Alpha1-PI for 13 weeks

Group Type EXPERIMENTAL

90 mg/kg Alpha1-PI

Intervention Type BIOLOGICAL

Placebo, 13 weeks

Weekly infusions of placebo for 13 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

Interventions

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180 mg/kg Alpha1-PI

Intervention Type BIOLOGICAL

90 mg/kg Alpha1-PI

Intervention Type BIOLOGICAL

Placebo

Intervention Type BIOLOGICAL

Other Intervention Names

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Alpha1-antitrypsin Prolastin-C Alpha1-Proteinase Inhibitor (human), Modified Process Alpha-1 MP Alpha1-antitrypsin Prolastin-C Alpha1-Proteinase Inhibitor (human), Modified Process Alpha-1 MP

Eligibility Criteria

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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.
Minimum Eligible Age

6 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Grifols Therapeutics LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Arizona

Tucson, Arizona, United States

Site Status

Clinica Medica San Miguel

Los Angeles, California, United States

Site Status

Diabetes Associates Medical Group

Orange, California, United States

Site Status

Rady Children's Hospital San Diego

San Diego, California, United States

Site Status

Metabolic Institute of America

Tarzana, California, United States

Site Status

Ronald H Chochinov MD

Ventura, California, United States

Site Status

Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

Christiana Care Health Services

Newark, Delaware, United States

Site Status

Solutions Through Advanced Research Inc.

Jacksonville, Florida, United States

Site Status

CCM Clinical Research

Miami, Florida, United States

Site Status

Advanced Pharma CR LLC

Miami, Florida, United States

Site Status

Atlanta Diabetes Associates

Atlanta, Georgia, United States

Site Status

Rocky Mountain Diabetes and Osteoporosis Center

Idaho Falls, Idaho, United States

Site Status

Cook County Hospital

Chicago, Illinois, United States

Site Status

Methodist Research Institute

Indianapolis, Indiana, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

Barry J. Reiner MD, LLC.

Baltimore, Maryland, United States

Site Status

UMass Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

Wayne State University

Detroit, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota

Saint Paul, Minnesota, United States

Site Status

Morristown Medical Center

Morristown, New Jersey, United States

Site Status

University of New Mexico, Health Sciences Center

Albuquerque, New Mexico, United States

Site Status

Women and Children's Hospital

Buffalo, New York, United States

Site Status

WakeMed Children's Hospital

Raleigh, North Carolina, United States

Site Status

Endocrinology Associates Inc

Columbus, Ohio, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

Pediatric Endocrinology, Genetics & Metabolism

Oklahoma City, Oklahoma, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Rapid City Regional Hospital/Health Clinical Research

Rapid City, South Dakota, United States

Site Status

Research Institute of Dallas

Dallas, Texas, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Northeast Clinical Research of San Antonio LLC

San Antonio, Texas, United States

Site Status

University of Texas Health Science Center

San Antonio, Texas, United States

Site Status

Consano Clinical Research

San Antonio, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 33244872 (View on PubMed)

Other Identifiers

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GTI1302

Identifier Type: -

Identifier Source: org_study_id

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