Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

August 16, 2010
January 14, 2015
October 2010
July 2013   (final data collection date for primary outcome measure)
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.
Mixed-Meal Tolerance Test (MMTT)-stimulated 2-hour C-peptide Area under the curve (AUC) [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01183468 on ClinicalTrials.gov Archive Site
Not Provided
  • 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)
Effect of Intravenous Alpha-1 Antitrypsin on Preserving Beta-cell Function in New-onset Type 1 Diabetes Mellitus (ITN041AI)

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.

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).

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Diabetes Mellitus, Type 1
  • 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
  • Biological: Aralast NP 180 mg dose
    - 180 mg/kg/week
    Other Names:
    • Alpha-1 Antitrypsin
    • AAT
  • 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.
    Interventions:
    • Biological: Aralast NP 45 mg dose
    • Biological: Aralast NP 90 mg dose
  • 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.
    Interventions:
    • Biological: Aralast NP 45 mg dose
    • Biological: Aralast NP 90 mg dose
  • 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.
    Interventions:
    • Biological: Aralast NP 90 mg dose
    • Biological: Aralast NP 180 mg dose
  • 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.
    Interventions:
    • Biological: Aralast NP 90 mg dose
    • Biological: Aralast NP 180 mg dose
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.
 
Terminated
17
July 2013
July 2013   (final data collection date for primary outcome measure)

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.
Both
8 Years to 35 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01183468
DAIT ITN041AI Part 1
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)
January 2015

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