Treatment With hOKT3gamma1(Ala-Ala) in T1DM
- Registration Number
- NCT00806572
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 10
- 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).
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment hOKT3gamma1(Ala-Ala) -
- Primary Outcome Measures
Name Time Method 4-hour C-peptide AUC 24 months
- Secondary Outcome Measures
Name Time Method Insulin usage throughout study
Trial Locations
- Locations (3)
University of California San Francisco
🇺🇸San Francisco, California, United States
Benaroya Research Institute
🇺🇸Seattle, Washington, United States
Naomie Berrie Diabetes Center, Columbia University
🇺🇸New York, New York, United States