Clinical trial NCT00806572: Treatment With hOKT3gamma1(Ala-Ala) in T1DM
Official title: Phase II Multiple Dose Treatment of Type 1 Diabetes Mellitus With hOKT3gamma1(Ala-Ala)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 1
Keywords: Diabetes, juvenile diabetes, teplizumab
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Immune Tolerance Network (ITN)
First posted: 2008-12-11
Enrollment: 10
Sex: ALL
Minimum age (years): 7
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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 tests listed and as defined by the protocol.

Primary outcomes:
measure: 4-hour C-peptide AUC
timeFrame: 24 months
Secondary outcomes:
measure: Insulin usage
timeFrame: throughout study
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: New York
country: United States
facility: Naomie Berrie Diabetes Center, Columbia University
state: New York
city: Seattle
country: United States
facility: Benaroya Research Institute
state: Washington
Study officials:
affiliation: Yale University
name: Kevan C Herold, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Herold KC, Gitelman S, Greenbaum C, Puck J, Hagopian W, Gottlieb P, Sayre P, Bianchine P, Wong E, Seyfert-Margolis V, Bourcier K, Bluestone JA; Immune Tolerance Network ITN007AI Study Group. Treatment of patients with new onset Type 1 diabetes with a single course of anti-CD3 mAb Teplizumab preserves insulin production for up to 5 years. Clin Immunol. 2009 Aug;132(2):166-73. doi: 10.1016/j.clim.2009.04.007. Epub 2009 May 14.