Treatment With hOKT3gamma1(Ala-Ala) in T1DM - Full Text View

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:	NCT00806572

Purpose

This is a phase II study to examine the clinical and immunological effects of humanized FcR non-binding anti-CD3 mAb in participants with Type 1 diabetes mellitus (T1DM), and to develop this therapy to prevent the immune destruction leading to β cell loss.

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

MedlinePlus related topics: Diabetes Diabetes Type 1

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Efficacy Study
Official Title:	Phase II Multiple Dose Treatment of Type 1 Diabetes Mellitus With hOKT3gamma1(Ala-Ala)

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

Primary Outcome Measures:

4-hour C-peptide AUC [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Insulin usage [ Time Frame: throughout study ] [ Designated as safety issue: No ]

Enrollment:	10
Study Start Date:	May 2002
Study Completion Date:	August 2007
Primary Completion Date:	July 2004 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Treatment: Experimental	Drug: hOKT3gamma1(Ala-Ala) 3 cycles, six months apart, each consisting of 12 daily infusions with 455-1818ug/m2 hOKT3g1(Ala-Ala)
Control: No Intervention

Detailed Description:

This is a 2-arm, open-label phase II trial involving 0 or 3 cycles of treatment 6 months apart with hOKT3γ1 (Ala-Ala), over the first year of disease in participants with new onset T1DM. Each cycle consists of 12 daily doses of hOKT3γ1 (Ala-Ala).

Participants will be randomized in a ratio of 2:1 to either the experimental arm or the control arm and will be stratified by study site.

To be eligible, participants must be: male or female between 7-30 years of age, diagnosed with T1DM within the past 6 weeks, have a body weight ≥26 kg at the time of enrollment and have detectable anti-GAD, anti-ICA512/IA-2, or insulin autoantibodies (if the participant has been on insulin ≤10 days). Participants randomized to the experimental group will start the first cycle of hOKT3γ1 (Ala-Ala) within 4-8 weeks of T1DM diagnosis. Each participant randomized to the experimental group will receive 3 cycles of drug treatment, separated by 6 months each. Each cycle consists of 12 days of drug treatment. Both groups will undergo the Mixed Meal Stimulated C-Peptide Test and receive blood draws for mechanistic studies on the same schedule.

Eligibility

Ages Eligible for Study:	7 Years to 30 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

diagnosed with T1DM within the past 6 weeks
have a body weight ≥26 kg at the time of enrollment
have detectable anti-GAD, anti-ICA512/IA-2, or insulin autoantibodies (if the participant has been on insulin ≤10 days).

Exclusion Criteria:

Pregnant or lactating females;
Prior OKT3 treatment;
Known hypersensitivity to murine products;
Uncompensated heart failure or fluid overload, recent myocardial infarction;
History of epilepsy, cancer, active infection, atopic disease, active Grave's disease, cystic fibrosis, sickle cell anemia, neuropathy, peripheral vascular disease, cerebrovascular disease, any concurrent autoimmune diseases, asthma;
Any medical condition that in the opinion of the investigator will interfere with safe completion of the trial;
Inability to give informed consent;
Prior participation in a clinical trial that could potentially affect diabetes or immunologic status;
Participation in a clinical trial within the last 6 weeks;
HIV positive;
Positive for Hepatitis B surface antigen or Anti-Hepatitis C antibody;
Seropositivity for Toxoplasmosis (IgG);
Lymphopenia (<1000 lymphocytes/microliter);
Thrombocytopenia (<150,000/mm3 platelets);
Anemia (Hgb < 10g/dL);
Vaccination with a live virus within the past 6 weeks;
Positive PPD skin test;
Any infectious mononucleosis-like illness within the 3 months prior to enrollment;
Serologic evidence of acute infection with EBV or CMV based on studies listed; below in 5.1.1 and 5.1.4.3 (f).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00806572

Locations

United States, California
University of California San Francisco
San Francisco, California, United States, 94143
United States, New York
Naomie Berrie Diabetes Center, Columbia University
New York, New York, United States, 10032
United States, Washington
Benaroya Research Institute
Seattle, Washington, United States, 98101

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Immune Tolerance Network

Investigators

Principal Investigator:

Kevan C Herold, MD

Yale University

More Information

Additional Information:

Immune Tolerance Network This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	DAIT/NIAID ( Associate Director, Clinical Research Program )
Study ID Numbers:	ITN007AI, NDB01
Study First Received:	December 9, 2008
Last Updated:	December 9, 2008
ClinicalTrials.gov Identifier:	NCT00806572 History of Changes
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, juvenile diabetes, teplizumab

Study placed in the following topic categories:

Autoimmune Diseases
Metabolic Diseases
Diabetes Mellitus, Type 1
Diabetes Mellitus
Endocrine System Diseases

Diabetes Mellitus Type 1
Endocrinopathy
Glucose Metabolism Disorders
Metabolic Disorder

Additional relevant MeSH terms:

Autoimmune Diseases
Metabolic Diseases
Immune System Diseases
Diabetes Mellitus, Type 1

Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders

ClinicalTrials.gov processed this record on May 06, 2009