Treatment With hOKT3gamma1(Ala-Ala) in T1DM

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Multiple Dose Treatment of Type 1 Diabetes Mellitus With hOKT3gamma1(Ala-Ala)

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: hOKT3gamma1(Ala-Ala)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br> | Drug: hOKT3gamma1(Ala-Ala)<br>* 3 cycles, six months apart, each consisting of 12 daily infusions with 455-1818ug/m2 hOKT3g1(Ala-Ala)<br>* Other names: teplizumab;|
| No Intervention: Control<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 4-hour C-peptide AUC |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin usage |  | throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, juvenile diabetes, teplizumab