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A Research Trial of Aralast in New Onset Diabetes (RETAIN)

This study has been terminated.
(Due to lack of mechanistic signal and competing industry studies)
Sponsor:
Collaborators:
Immune Tolerance Network (ITN)
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01183468
First received: August 16, 2010
Last updated: January 14, 2015
Last verified: January 2015
  Purpose

The drug Alpha-1 Antitrypsin (AAT, Aralast NP) is being tested in this study as an anti-inflammatory drug (a medication that decreases inflammation, which is part of the body's normal ability to fight infection and respond to injuries) that affects the cells thought to be involved in the development of type 1 diabetes mellitus (T1DM, T1D).

All subjects enrolled in this study have new-onset T1DM (diagnosis of T1DM within 100 days of Visit 0; T1DM diagnosis fulfilling American Diabetes Association standard T1DM criteria). The focus of Part I of this trial (NCT01183468) is pharmacokinetics (PK), pharmacodynamics (PD) and safety. Upon completion of Part I, including a satisfactory safety review, enrollment in Part II (NCT01183455, Phase II Clinical Trial) will begin.


Condition Intervention Phase
Diabetes Mellitus, Type 1
Biological: Aralast NP 45 mg dose
Biological: Aralast NP 90 mg dose
Biological: Aralast NP 180 mg dose
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Intravenous Alpha-1 Antitrypsin on Preserving Beta-cell Function in New-onset Type 1 Diabetes Mellitus (ITN041AI)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • C-peptide 2-hour AUC in Response to a Mixed-meal Tolerance Test at Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    No results for the primary outcome measure are available since the study was terminated prior to reaching the outcome measure time frame of 52 weeks.


Enrollment: 17
Study Start Date: October 2010
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1a(Aralast NP)-Subjects Aged 16-35 Yrs
Subjects aged 16-35 years at enrollment with new-onset type 1 diabetes mellitus (T1DM) received Aralast NP 45 mg/kg by intravenous (IV) infusion once a week for 6 weeks. Following the Week 6 infusion, participants underwent a minimum 3-week washout period. After the washout period, each participant proceeded to a high dose of Aralast NP 90 mg/kg by IV infusion for the next 6 weeks, for a total of 12 infusions.
Biological: Aralast NP 45 mg dose
- 45 mg/kg/week
Other Names:
  • Alpha 1-Antitrypsin
  • AAT
Biological: Aralast NP 90 mg dose
- 90 mg/kg/week
Other Names:
  • Alpha 1-Antitrypsin
  • AAT
Experimental: Part 1a (Aralast NP)-Subjects 8-15 Yrs
Subjects aged 8-15 years at enrollment with new-onset type 1 diabetes mellitus (T1DM) received Aralast NP 45 mg/kg by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants underwent a minimum 3-week washout period. After the washout period, each participant proceeded to a high dose of Aralast NP 90 mg/kg by IV infusion for the next 6 weeks, for a total of 12 infusions.
Biological: Aralast NP 45 mg dose
- 45 mg/kg/week
Other Names:
  • Alpha 1-Antitrypsin
  • AAT
Biological: Aralast NP 90 mg dose
- 90 mg/kg/week
Other Names:
  • Alpha 1-Antitrypsin
  • AAT
Experimental: Part 1b (Aralast NP)--Subjects Aged 18-35 Yrs
Aralast NP 90 mg/kg/wk by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants undergo a minimum 3-wk washout period than then, each participant proceeds to high dose Aralast NP 180 mg/kg/wk by IV infusion for the next 6 weeks, for a total of 12 infusions.
Biological: Aralast NP 90 mg dose
- 90 mg/kg/week
Other Names:
  • Alpha 1-Antitrypsin
  • AAT
Biological: Aralast NP 180 mg dose
- 180 mg/kg/week
Other Names:
  • Alpha-1 Antitrypsin
  • AAT
Experimental: Part 1b (Aralast NP)-Subjects 8-17 Yrs
Aralast NP 90 mg/kg/wk by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants undergo a minimum 3-wk washout period than then, each participant proceeds to high dose Aralast NP 180 mg/kg/wk by IV infusion for the next 6 weeks, for a total of 12 infusions.
Biological: Aralast NP 90 mg dose
- 90 mg/kg/week
Other Names:
  • Alpha 1-Antitrypsin
  • AAT
Biological: Aralast NP 180 mg dose
- 180 mg/kg/week
Other Names:
  • Alpha-1 Antitrypsin
  • AAT

Detailed Description:

Researchers are interested in conducting this study to assess whether Aralast NP (AAT, Alpha-1 Antitrypsin ) will help slow the progression of T1DM.

Part I of this study has two parts:-1a and -1b:

Part 1a (Complete): An open-label, dose-escalation, PK, PD and safety study. Participants receive 12 intravenous (IV) infusions of Aralast NP. Infusions 1 through 6 are administered at 45 mg/kg/wk and infusions 7 through 12 are administered at 90 mg/kg/wk.

Part Ia consists of two groups:

  • Subjects aged 16 - 35 years at enrollment with new-onset T1DM
  • Subjects aged 8 -15 years at enrollment with new-onset T1DM.

Part 1b (study terminated prior to subject enrollment): An open-label, dose-escalation PK, PD and safety study in which participants receive 12 infusions of Aralast NP. Infusions 1 through 6 are administered at 90 mg/kg/wk and infusions 7 through 12 are administered at 180 mg/kg/wk. Part Ib consists of two groups:

  • Subjects aged 16 - 35 years at enrollment with new-onset T1DM
  • Subjects 8 - 15 years at enrollment with new-onset T1DM.

Participants in Part Ib do not roll over into Part II (Refer to NCT01183455).

  Eligibility

Ages Eligible for Study:   8 Years to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosed with T1DM within the past 100 days (of enrollment)
  • Positive for at least one diabetes-related autoantibody (Anti-GAD; Anti-insulin, if obtained within 10 days of the onset of insulin therapy; IA-2 antibody and/or ICA, or ZnT8.)
  • Peak stimulated C-peptide level > 0.2 pmol/mL following a mixed meal tolerance test (MMTT)

Exclusion Criteria:

  • Severe active disease (chronic active hepatitis; cardiac, pulmonary disease, hepatic, renal or immunodeficiency)
  • History of any bleeding or clotting factor deficiencies, or stroke
  • History of vascular disease or significant vascular abnormalities
  • Positive serology of exposure to (hepatitis B virus) HBV, HCV (hepatitis C virus), HIV (human immunodeficiency virus) or toxoplasmosis
  • Clinically active infection with EBV (Epstein-Barr virus), CMV (cytomegalovirus), or tuberculosis(TB)
  • Prior or current use of oral, inhaled or intranasal glucocorticoids, or any medication known to cause a significant, ongoing change in the course of T1DM or immunologic status
  • Prior treatment with Alpha 1-Antitrypsin (Aralast NP, AAT) or hypersensitivity to alpha 1-antitrypsin or human plasma-derived products
  • Current or prior (within the last 30 days) use of metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors or amylin
  • Current use of any medication known to influence glucose tolerance (e.g., beta-blockers, angiotensin-converting enzyme inhibitors, interferons, quinidine anti-malarial drugs, lithium, niacin)
  • Females who are pregnant or lactating, or are unwilling to defer pregnancy during study participation
  • IgA (immunoglobulin A) deficiency
  • Uncontrolled hypertension
  • Current life-threatening malignancy
  • Any condition that in the investigator's opinion may compromise study participation or may confound the interpretation of the study results.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01183468

Locations
United States, California
RADY Children's Hospital (University of California, San Diego)
San Diego, California, United States, 92093
United States, Colorado
Barbara Davis Center (University of Colorado)
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
United States, Georgia
Atlanta Diabetes Associates
Atlanta, Georgia, United States, 30309
Children's Hospital of Atlanta (Emory University)
Atlanta, Georgia, United States, 30322
United States, Iowa
University of Iowa Children's Hospital
Iowa City, Iowa, United States, 52242
United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Joslin Diabetes Center
Boston, Massachusetts, United States, 02215
University of Massachusetts Memorial Medical Center
Worchester, Massachusetts, United States, 01655
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
United States, New York
Naomi Berrie Diabetes Center (Columbia University)
New York, New York, United States, 10032
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Washington
Pacific Northwest Research Institute-University of Washington
Seattle, Washington, United States, 98122
Sponsors and Collaborators
Immune Tolerance Network (ITN)
Juvenile Diabetes Research Foundation
Investigators
Study Chair: Gordon Weir, MD Joslin Diabetes Center
  More Information

Additional Information:
No publications provided by National Institute of Allergy and Infectious Diseases (NIAID)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01183468     History of Changes
Other Study ID Numbers: DAIT ITN041AI Part 1
Study First Received: August 16, 2010
Results First Received: January 6, 2015
Last Updated: January 14, 2015
Health Authority: United States: Data and Safety Monitoring Board
United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Diabetes Mellitus, Type 1 (new-onset)
Diabetes Mellitus, Insulin-Dependent (new-onset)
new-onset T1DM
new-onset T1D
Diabetes Mellitus, Juvenile-Onset
Diabetes, Autoimmune
Aralast NP
Alpha-1 Antitrypsin
AAT

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Alpha 1-Antitrypsin
Protein C Inhibitor
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Serine Proteinase Inhibitors
Trypsin Inhibitors

ClinicalTrials.gov processed this record on February 25, 2015