Trial record 2 of 1530 for:    retain

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

This study has suspended participant recruitment.
(Pending an efficacy review)
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: February 25, 2014
Last verified: February 2014

August 16, 2010
February 25, 2014
October 2010
November 2016   (final data collection date for primary outcome measure)
Mixed-Meal Tolerance Test (MMTT)-stimulated 2-hour C-peptide Area under the curve (AUC) [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01183468 on ClinicalTrials.gov Archive Site
  • MMTT-stimulated peak and 4-hour C-peptide AUC [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
  • MMTT-stimulated 2-hour C-peptide AUC assessed longitudinally [ Time Frame: Weeks 0, 14, 26, 52, and 104 ] [ Designated as safety issue: No ]
  • Insulin use in units per kilogram body weight per day [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
    Insulin use in units per kilogram body weight per day
  • Hypoglycemic Events [ Time Frame: Enrollment to Week 104 ] [ Designated as safety issue: Yes ]
  • Glycosylated Hemoglobin (HbA1C) Levels [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: Yes ]
  • Emergence of anti-AAT antibodies [ Time Frame: Enrollment to Week 104 ] [ Designated as safety issue: Yes ]
  • Frequency and severity of all AEs (including infusion reactions, hypersensitivity reactions, and viral infections) [ Time Frame: Enrollment to Week 104 ] [ Designated as safety issue: Yes ]
  • Changes in D-dimer levels indicating alteration in coagulant/anticoagulant balance [ Time Frame: Enrollment to Week 104 ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic parameters of Aralast NP [ Time Frame: Enrollment to Week 104 ] [ Designated as safety issue: No ]
  • MMTT-stimulated peak and 4-hour C-peptide AUC [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
  • MMTT-stimulated 2-hour C-peptide AUC assessed longitudinally [ Time Frame: Weeks 0, 14, 26, 52, and 104 ] [ Designated as safety issue: No ]
  • Insulin use in units per kilogram body weight per day [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
    Insulin use in units per kilogram body weight per day
  • Hypoglycemic events occurring from randomization [ Time Frame: Throughout the trial ] [ Designated as safety issue: Yes ]
  • Glycosylated hemoglobin (HbA1C) levels [ Time Frame: Weeks 52 and 104 ] [ Designated as safety issue: No ]
  • Emergence of anti-AAT antibodies [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
  • Frequency and severity of all AEs (including infusion reactions, hypersensitivity reactions, and viral infections) [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
  • Changes in D-dimer levels indicating alteration in coagulant/anticoagulant balance [ Time Frame: Throughout the trial ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic parameters of Aralast NP [ Time Frame: Throughout the trial ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Research Trial of Aralast in New Onset Diabetes (RETAIN) - Part I
Effect of Intravenous Alpha-1 Antitrypsin on Preserving Beta-cell Function in New-onset Type 1 Diabetes Mellitus - Part I (ITN041AI)

The drug Alpha-1 Antitrypsin (AAT) which is being tested in this research study is 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 that are thought to be involved in the development of type 1 diabetes. Researchers are doing this study to see whether AAT will help slow the progression of type 1 diabetes.

Currently, Part I.b. is open and enrolling. Please see the detailed description for more information on this portion of the study.

This study has two parts, Part I.a. and Part I.b.:

  • Part I.a. (Complete): The first portion of Part I was an open-label, dose-escalation, pharmacokinetic (PK) and safety study in which participants received 12 infusions of Aralast NP. Infusions 1 through 6 were administered at 45 mg/kg/wk and infusions 7 through 12 were administered at 90 mg/kg/wk. Participants enrolled in Part Ia will not roll over to Part Ib. Part Ia consisted of two cohorts:

    • Adult cohort: The first cohort had 8 participants, age 16-35 years, with new-onset T1DM. These participants received Aralast NP 45 mg/kg via IV infusion once a week for 6 weeks. One participant discontinued before the low dose infusion was complete. After completing the week-6 infusion, the remaining 7 participants underwent a 3-week washout period during which his or her safety data was reviewed by the protocol chair, the NIAID medical monitor, and the ITN clinical trial physician. No individual stopping rule had been met as defined in Section 5.2. Subsequently, each participant proceeded to the higher dose of 90 mg/kg/wk for the next 6 weeks, for a total of 12 infusions. When all participants completed 12 weeks of infusions, a second safety review was performed.
    • Pediatric cohort: After 6 participants in the adult cohort underwent the safety review and proceeded to the high dose, the pediatric cohort began to enroll. This cohort was comprised of 8 pediatric participants, age 8-15 years, with new-onset T1DM. These participants received Aralast NP 45 mg/kg via IV infusion once a week for 6 weeks. One participant did not receive the 4th low-dose infusion (elevated D-dimer level) but completed all other infusions. After completing the week-6 infusion, each participant underwent a minimum 3-week washout period during which his or her safety data were reviewed by the protocol chair, the NIAID medical monitor, and the ITN clinical trial physician. No individual stopping rule had been met as defined in Section 5.2. When at least 6 participants from the pediatric cohort safely completed the low dose and at least 6 participants from the adult cohort safely completed the high dose, dose escalation to 90 mg/kg/wk in the pediatric cohort proceeded for the next 6 weeks. A total of 12 infusions were given as outlined for the adult cohort. When all participants completed 12 weeks of infusions, a second safety review was performed.
  • Part I.b.: This part of the trial is an open-label, dose-escalation, pharmacokinetic (PK) and safety study in which participants will receive 12 infusions of Aralast NP. Infusions 1 through 6 will be administered at 90 mg/kg/wk and, infusions 7 through 12 will be administered at 180 mg/kg/wk. Participants in Part Ib will not roll over into Part II. Part Ib consists of two cohorts:

    • Adult cohort: The first cohort will be comprised of 8 participants, age 18-35 years, with new-onset T1DM. Part Ib participants will receive Aralast NP 90 mg/kg via IV infusion once a week for 6 weeks. After completing the week-6 infusion, each participant will undergo a 3-week washout period. Subsequently, each participant will proceed to the higher dose of 180 mg/kg/wk for the next 6 weeks, for a total of 12 infusions. When all participants have completed 12 weeks of infusions, a safety review will be performed.
    • Pediatric cohort: After 6 participants in the adult cohort have proceeded to the high dose, the pediatric cohort may begin to enroll. This cohort will be comprised of 8 pediatric participants, age 8-17 years, with new-onset T1DM. These participants will receive Aralast NP 90 mg/kg via IV infusion once a week for 6 weeks. After completing the week-6 infusion, each participant will undergo a minimum 3-week washout period. When at least 6 participants from the pediatric cohort have safely completed the low dose and at least 6 participants from the adult cohort have safely completed the high dose, dose escalation to 180 mg/kg/wk in the pediatric cohort may proceed for the next 6 weeks. A total of 12 infusions will be given as outlined for the adult cohort. When all participants have completed 12 weeks of infusions, a second safety review will be performed.
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Diabetes Mellitus, Type 1
  • Biological: Alpha 1-Antitrypsin
    - 45 mg/kg/week
    Other Names:
    • AAT
    • Aralast NP
  • Biological: Alpha-1 Antitrypsin
    - 90 mg/kg/week
  • Biological: Alpha-1 Antitrypsin
    - 180 mg/kg/week
  • Experimental: Part 1.a. - Adult
    Interventions:
    • Biological: Alpha 1-Antitrypsin
    • Biological: Alpha-1 Antitrypsin
  • Experimental: Part 1.a. - Pediatric
    Interventions:
    • Biological: Alpha 1-Antitrypsin
    • Biological: Alpha-1 Antitrypsin
  • Experimental: Part 1.b. - Adult
    Interventions:
    • Biological: Alpha-1 Antitrypsin
    • Biological: Alpha-1 Antitrypsin
  • Experimental: Part 1.b. - Pediatric
    Interventions:
    • Biological: Alpha-1 Antitrypsin
    • Biological: Alpha-1 Antitrypsin
Ozeri E, Mizrahi M, Shahaf G, Lewis EC. α-1 antitrypsin promotes semimature, IL-10-producing and readily migrating tolerogenic dendritic cells. J Immunol. 2012 Jul 1;189(1):146-53. doi: 10.4049/jimmunol.1101340. Epub 2012 May 25.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Suspended
32
November 2017
November 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosed with type 1 diabetes within the past 100 days
  • 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:

  • Serve active disease (hepatitis, cardiac or pulmonary disease, hypertension, immunodeficiency)
  • History of any bleeding or clotting factor deficiencies, or stroke
  • History of vascular disease or significant vascular abnormalities
  • Positive serology exposure to HBV, HCV, HIV or toxoplasmosis
  • Clinically active infection with EBV, CMV, or tuberculosis
  • 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 AAT or hypersensitivity to AAT 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 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.
Both
8 Years to 35 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01183468
DAIT ITN041AI
Yes
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
  • Immune Tolerance Network (ITN)
  • Juvenile Diabetes Research Foundation
Study Chair: Gordon Weir, MD Joslin Diabetes Center
National Institute of Allergy and Infectious Diseases (NIAID)
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP