Diabetes Mellitus, Type 1
Conditions
Keywords
Diabetes, juvenile diabetes, teplizumab
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.
Interventions
3 cycles, six months apart, each consisting of 12 daily infusions with 455-1818ug/m2 hOKT3g1(Ala-Ala)
Sponsors
Immune Tolerance Network (ITN)
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 30 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 4-hour C-peptide AUC | 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Insulin usage | throughout study |
Countries
United States
Outcome results
None listed