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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Withdrawn

CT.gov ID

NCT01183455

Collaborator

Immune Tolerance Network (ITN) (Other), Juvenile Diabetes Research Foundation (Other)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: Aralast NP Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Effect of Intravenous Alpha-1 Antitrypsin on Preserving Beta-cell Function in New-onset Type 1 Diabetes Mellitus (ITN041AI)- Part II

Study Start Date :

Oct 1, 2010

Actual Primary Completion Date :

Aug 1, 2014

Actual Study Completion Date :

Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aralast NP Participants will receive Aralast NP (90mg/kg) intravenously once a week for 12 weeks.	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
Placebo Comparator: Placebo Participants will receive placebo intravenously once a week for 12 weeks.	Drug: Placebo Participants will receive IV infusions of placebo once a week for 12 weeks. Other Names: Placebo for Aralast NP

Arm

Intervention/Treatment

Experimental: Aralast NP

Participants will receive Aralast NP (90mg/kg) intravenously once a week for 12 weeks.

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

Placebo Comparator: Placebo

Participants will receive placebo intravenously once a week for 12 weeks.

Drug: Placebo

Participants will receive IV infusions of placebo once a week for 12 weeks.

Other Names:

Placebo for Aralast NP

Outcome Measures

Primary Outcome Measures

Mixed-Meal Tolerance Test (MMTT)-Stimulated 2-hour C-peptide Area Under the Curve (AUC) [Week 52]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years to 35 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Diego	La Jolla	California	United States	92093
2	Barbara Davis Center	Aurora	Colorado	United States	80045
3	Yale University	New Haven	Connecticut	United States	06511
4	Atlanta Diabetes Associates	Atlanta	Georgia	United States	30309
5	Emory University	Atlanta	Georgia	United States	30322
6	University of Iowa	Iowa City	Iowa	United States	52242
7	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
8	Calvert Memorial Hospital	Prince Frederick	Maryland	United States	20678
9	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
10	Joslin Diabetes Center	Boston	Massachusetts	United States	02215
11	University of Massachusetts Medical School	Worchester	Massachusetts	United States	01655
12	Columbia University	New York	New York	United States	10027
13	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
14	The Children's Hospital of Philadelphia	Philadephia	Pennsylvania	United States	19104
15	Cetero Research San Antonio	San Antonio	Texas	United States	78229