Autoimmunity-Blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes (AbATE)

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Autoimmunity-Blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes (AbATE)

This study is currently recruiting participants.
Verified by National Institute of Allergy and Infectious Diseases (NIAID), December 2008
Sponsors and Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Immune Tolerance Network

Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00129259

Purpose
hOKT3gamma1 (Ala-Ala) is a man-made antibody that is commonly used to prevent organ rejection. The purpose of this study is determine whether hOKT3gamma1 (Ala-Ala) can halt the progression of newly diagnosed type 1 diabetes.

Condition Intervention Phase
Diabetes Mellitus, Type 1
Drug: hOKT3gamma1 (Ala-Ala)
Other: Intensive diabetes management
Phase II

MedlinePlus related topics: Diabetes Diabetes Type 1
Drug Information available for: Insulin Immunoglobulins Globulin, Immune
U.S. FDA Resources
Study Type:Interventional
Study Design:Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:Phase II Multiple-Dose Treatment of New Onset Type 1 Diabetes Mellitus With hOKT3gammal (Ala-Ala)

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

Primary Outcome Measures:
Change from baseline of the mean C-peptide 4-hour area under the curve (AUC) in response to a mixed meal tolerance test (MMTT) [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
Diabetes-related endpoints, including insulin use, time to undetectable C-peptide response, and HbA1C level [ Time Frame: 24 months ] [ Designated as safety issue: No ]

pharmacokinetic measures, including drug levels, adverse events, Epstein-Barr virus (EBV)/cytomegalovirus (CMV) viral loads [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

mechanistic assessments, including T cell depletion/repopulation, alterations to cytokine levels, and T cell activation measures [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment:81
Study Start Date:September 2005
Estimated Study Completion Date:March 2011
Estimated Primary Completion Date:March 2011 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
1: Experimental Drug: hOKT3gamma1 (Ala-Ala)
daily 14-day dose escalation course (from 51 ug/m2 IV on day 1, to 826 ug/m2 on days 5-14) at study entry, with possible second course after 12-month interval
Other: Intensive diabetes management
Dietary counselling, insulin dosing and scheduling, multiple consultations with clinical diabetes management team
2: Active Comparator Other: Intensive diabetes management
Dietary counselling, insulin dosing and scheduling, multiple consultations with clinical diabetes management team

Detailed Description:
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks insulin-producing beta cells in the pancreas. Without these cells, the body cannot maintain proper blood glucose levels in response to daily activities, such as eating or exercise. Generally, at the time of type 1 diabetes diagnosis, 60% to 85% of the diabetic person's beta cells have already been destroyed. However, between 15% and 40% of these cells remain and are able to produce insulin. Treatment that slows the destruction of additional beta cells may be able to decrease a patient's reliance on insulin and improve their quality of life.

hOKT3gamma1 (Ala-Ala) is a genetically engineered monoclonal antibody directed against the CD3 antigen on T cells; this antibody selectively attacks the immune cells responsible for beta cell destruction. In a small exploratory clinical trial, patients with newly diagnosed type 1 diabetes who received a single, 2-week treatment with hOKT3gamma1 (Ala-Ala) had preserved beta cell function and significantly lower insulin requirements than untreated patients for up to two years after therapy. This study will investigate whether a second course of hOKT3gamma1 (Ala-Ala) administered one year after the first administration is able to prolong or improve the effects of the drug in people who have recently diagnosed type 1 diabetes mellitus.

Participants will be randomly assigned to one of two groups. Group 1 will receive hOKT3gamma1 (Ala-Ala) antibody treatment plus standard diabetes management; Group 2 will receive standard diabetes management alone. Group 1 will be treated with the antibody for the first 14 days of the study and again one year later. Group 1 participants will be admitted to the hospital for the first 5 days of a treatment cycle. Participants who live within 1 hour of the hospital may receive the remainder of a treatment cycle as an outpatient, but those who live farther away will be hospitalized for 14 days. For the first treatment cycle, there will be study visits on the 3 consecutive days after the treatment cycle and at Months 1, 2, 3, 6, 9, and 12. For the second treatment cycle, there will be study visits on the 3 consecutive days after the treatment cycle and at Months 13, 16, 19, 21, and 24. Group 2 will have 12 study visits over two years.

At study entry, all participants will receive daily iron supplementation, either as ferrous sulfate or a multivitamin with iron. Participants will be followed for up to 2 years to assess their overall diabetes health and to capture laboratory measures of beta cell and immune system function. Medication history and adverse event assessment will occur at all visits. A physical exam, vital signs measurement, and blood collection will occur at most visits. Medical history and urine collection will occur at selected visits.

Eligibility
Ages Eligible for Study:8 Years to 30 Years
Genders Eligible for Study:Both
Accepts Healthy Volunteers:No
Criteria
Inclusion Criteria:

Diagnosis of type 1 diabetes (according to American Diabetes Association [ADA] criteria) within the 8 weeks prior to study entry
Weigh at least 25 kg (55 lbs)
Insulin autoantibodies assessed within 10 days of any insulin use OR anti-glutamic acid decarboxylase (GAD) autoantibodies OR anti-ICA512/IA-2 autoantibodies
Parent or guardian willing to provide informed consent, if applicable
Exclusion Criteria:

Prior participation in a clinical trial that could potentially affect diabetes condition or immunologic status
Participation in another investigational clinical trial within the 6 weeks prior to study entry
Pregnancy or breastfeeding
Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00129259

Contacts
Contact: Kimberly Kunze 203-785-7407 info@abatetrial.org

Locations
United States, California
The Diabetes Center at UCSF Recruiting
San Francisco, California, United States, 94143
Contact: Christine Torok, RN 415-353-9089 ucsf@abatetrial.org
Contact: Kathleen Fraser (415) 353-9084 kfraser@diabetes.ucsf.edu
Principal Investigator: Stephen Gitelman, MD
Principal Investigator: Umesh Masarani, MD
United States, Colorado
Barbara Davis Center for Childhood Diabetes Recruiting
Denver, Colorado, United States, 80262
Contact: Meyer Belzer 303-724-6758 bdavis@abatetrial.org
Principal Investigator: Peter Gottlieb, MD
United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06520
Contact: Linda Rink 203-737-4510 info@abatetrial.org
Contact: Kimberly Kunze 203-785-7407 Kimberly.Kunze@Yale.edu
Principal Investigator: Kevan Herold, MD
Principal Investigator: Stuart Weinzimer, MD
United States, Georgia
Medical College of Georgia Active, not recruiting
Augusta, Georgia, United States, 30912
United States, Washington
Benaroya Research Institute Recruiting
Seattle, Washington, United States, 98108
Contact: Marli McCulloch-Olson 206-515-5233 benaroya@abatetrial.org
Principal Investigator: Carla Greenbaum, MD
Pacific Northwest Research Institute/University of Washington Recruiting
Seattle, Washington, United States, 98122
Contact: Katrina Dziubkiewicz, RN,BSN,CDE 206-568-1485 pnri@abatetrial.org
Principal Investigator: William Hagopian, MD

Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Immune Tolerance Network
Investigators
Principal Investigator: Kevan Herold, MD Yale University

Publications:
Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D, Rother K, Diamond B, Harlan DM, Bluestone JA. A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes. 2005 Jun;54(6):1763-9.
Herold KC, Hagopian W, Auger JA, Poumian-Ruiz E, Taylor L, Donaldson D, Gitelman SE, Harlan DM, Xu D, Zivin RA, Bluestone JA. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med. 2002 May 30;346(22):1692-8.

Responsible Party:DAIT/NIAID ( Associate Director, Clinical Research Program )
Study ID Numbers:ITN027AI
First Received:August 9, 2005
Last Updated:December 9, 2008
ClinicalTrials.gov Identifier:NCT00129259 [history]
Health Authority:United States: Food and Drug Administration; United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
diabetes
type 1 diabetes
diabetes mellitus
juvenile diabetes
autoimmune diabetes
type 1
juvenile
autoimmune
hOKT3
hOKT3g1
hOKT3g1(Ala-Ala)

Study placed in the following topic categories:
Antibodies
Autoimmune Diseases
Metabolic Diseases
Diabetes Mellitus, Type 1
Diabetes Mellitus
Endocrine System Diseases
Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders
Insulin
Immunoglobulins

Additional relevant MeSH terms:
Immune System Diseases