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

• ClinicalTrials.gov Identifier: NCT01183455
• Recruitment Status: Withdrawn
• First Posted: August 17, 2010
• Last Update Posted: December 31, 2014
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Immune Tolerance Network (ITN); Juvenile Diabetes Research Foundation
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information

• First Submitted Date: August 16, 2010
• First Posted Date: August 17, 2010
• Last Update Posted Date: December 31, 2014
• Study Start Date: October 2010
• Actual Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 20, 2014): Mixed-Meal Tolerance Test (MMTT)-Stimulated 2-hour C-peptide Area Under the Curve (AUC) [ Time Frame: Week 52 ]
• Original Primary Outcome Measures (submitted: August 16, 2010): Mixed-Meal Tolerance Test (MMTT)-stimulated 2-hour C-peptide Area under the curve (AUC) [ Time Frame: Week 52 ]

Current Secondary Outcome Measures (submitted: October 20, 2014)

• MMTT-Stimulated Peak and 4-hour C-peptide AUC [ Time Frame: Weeks 52 and 104 ]
• MMTT-Stimulated 2-hour C-Peptide AUC Assessed Over Time [ Time Frame: Weeks 0, 14, 26, 52, and 104 ]
• Insulin Use in Units Per Kilogram Body Weight Per Day [ Time Frame: Weeks 52 and 104 ]
• Hypoglycemic Events Occurring from Randomization to End of Trial [ Time Frame: Throughout the Study ]
• Glycosylated Hemoglobin (HbA1c) Levels [ Time Frame: Weeks 52 and 104 ]
• Emergence of Anti-Alpha 1-Antitrypsin (AAT) Antibodies [ Time Frame: Throughout the Study ]
• Frequency and Severity of All Adverse Events (AEs) [ Time Frame: Throughout the study ]
• Changes in D-dimer Levels Indicating Alteration in Coagulant/Anticoagulant Balance [ Time Frame: Throughout the study ]
• Pharmacokinetic Parameters of Aralast NP [ Time Frame: Throughout the study ]

Original Secondary Outcome Measures (submitted: August 16, 2010)

• MMTT-stimulated peak and 4-hour C-peptide AUC [ Time Frame: Weeks 52 and 104 ]
• MMTT-stimulated 2-hour C-peptide AUC assessed longitudinally [ Time Frame: Weeks 0, 14, 26, 52, and 104 ]
• Insulin use in units per kilogram body weight per day [ Time Frame: Weeks 52 and 104 ]
• Hypoglycemic events occurring from randomization [ Time Frame: Throughout the trial ]
• Glycosylated hemoglobin (HbA1C) levels [ Time Frame: Weeks 52 and 104 ]
• Emergence of anti-AAT antibodies [ Time Frame: Throughout the study ]
• Frequency and severity of all AEs (including infusion reactions, hypersensitivity reactions, and viral infections) [ Time Frame: Throughout the trial ]
• Changes in D-dimer levels indicating alteration in coagulant/anticoagulant balance [ Time Frame: Throughout the trial ]
• Pharmacokinetic parameters of Aralast NP [ Time Frame: Throughout the trial ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Research Trial of Aralast NP in New Onset Diabetes (RETAIN) - Part II
• Official Title: Effect of Intravenous Alpha-1 Antitrypsin on Preserving Beta-cell Function in New-onset Type 1 Diabetes Mellitus (ITN041AI)- Part II

Brief Summary

Aralast NP (alpha-1 antitrypsin, AAT), an alpha-1 proteinase inhibitor (human), was the drug to be tested in this clinical trial. Aralast NP is an anti-inflammatory drug that affects the cells that are thought to be involved in the development of type 1 diabetes mellitus (T1DM, T1D). This study, known as RETAIN, was planned as a two-part trial to investigate the effect of Aralast NP on preserving beta cell function and to determine if the intervention would slow the progression of type 1 diabetes.

Part I of this trial (NCT 01183468) was an open-label, safety and dose level study consisting of two groups. After completion of Part I, including a satisfactory safety review, enrollment in Part II was to begin. Part II was designed as a two-arm, double-blind, placebo-controlled clinical trial, and participants were to be randomly assigned to either the Aralast NP treatment or placebo group.

Detailed Description

T1D is an autoimmune disease. This means that your immune system (the part of your body that helps fight infections) mistakenly attacks the cells that produce insulin (beta cells in the pancreas). As beta cells are destroyed by your immune cells, your ability to produce insulin is decreased. Insulin helps keep blood glucose levels normal.

Individuals with T1D who have the ability to produce some of their own insulin (even though they still need to take insulin) may be able to achieve better glucose control than people who produce no insulin at all. Better glucose control has been shown to reduce the long-term complications of diabetes. Previous research has shown that giving medicines to affect the immune system soon after type 1 diabetes is diagnosed may stop, delay or decrease the destruction of beta cells, resulting in better glucose control.

In mouse models of disease, alpha-1 proteinase inhibitors have been shown to reverse new-onset diabetes and induce a state of self-tolerance. The RETAIN clinical trial was intended to investigate the effect of Aralast NP on preserving beta cell function and slowing the progression of T1D.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Diabetes Mellitus, Type 1

Intervention

• Drug: Aralast NP
  Participants will receive IV infusions of Aralast NP (90mg/kg) once a week for 12 weeks.
  Other Names:

  • Alpha 1-Proteinase Inhibitor Human
  • Alpha,-antitrypsin
  • AAT
• Drug: Placebo
  Participants will receive IV infusions of placebo once a week for 12 weeks.
  Other Name: Placebo for Aralast NP

Study Arms

• Experimental: Aralast NP
  Participants will receive Aralast NP (90mg/kg) intravenously once a week for 12 weeks.
  Intervention: Drug: Aralast NP
• Placebo Comparator: Placebo
  Participants will receive placebo intravenously once a week for 12 weeks.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: October 20, 2014): 0
• Original Estimated Enrollment (submitted: August 16, 2010): 66
• Actual Study Completion Date: August 2014
• Actual Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosed with type 1 diabetes (T1D) 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 greater than (>) 0.2 pmol/mL following a mixed meal tolerance test (MMTT)

Exclusion Criteria:

• Severe 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 hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or toxoplasmosis
• Clinically active infection with Epstein-Barr virus (EBV), cytomegalovirus (CMV), 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 T1D or immunologic status
• Prior treatment with alpha1-antitrypsin (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
• Immunoglobulin A (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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 8 Years to 35 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01183455
• Other Study ID Numbers: DAIT ITN041AI Part II
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• Original Responsible Party: Associate Director, Clinical Research and Operations Program, DAIT, NIAID, NIH
• Current Study Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Original Study Sponsor: Same as current

Collaborators

• Immune Tolerance Network (ITN)
• Juvenile Diabetes Research Foundation

Investigators

• Study Chair: Gordon Weir, MD; Joslin Diabetes Center

• PRS Account: National Institute of Allergy and Infectious Diseases (NIAID)
• Verification Date: December 2014