Anti-CD3 mAb Treatment of Recent Onset Type 1 Diabetes

Study Overview
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Brief Summary
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This is a randomized placebo controlled study to test whether a single 14 course of treatment with the anti-CD3 monoclonal antibody, hOKT3gamma1(Ala-Ala),Teplizumab will prevent the loss of insulin secretory capacity in individuals with Type 1 diabetes of 4 - 12 months duration since diagnosis.

Detailed Description
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The study design is a double blind placebo controlled trial that will enroll subjects between the ages of 8 - 30 who have had the diagnosis of Type 1 diabetes made 4 - 12 months prior to enrollment. A single 14 course of treatment with mAb hOKT3gamma1(Ala-Ala), Teplizumab will be given. The primary endpoint is the C-peptide response to a mixed meal at 12 months. A total of 60 subjects will be enrolled (30 in the drug treatment and 30 in the placebo groups) at 4 study sites: Yale University,the University of California at San Francisco, Children's Hospital of Philadelphia, and the Barbara Davis Diabetes Center.

Official Title
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Phase II Trial of hOKT3gamma1(Ala-Ala) Teplizumab for Treatment of Patients With Recent Onset Type 1 Diabetes

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: mAb hOKT3gamma1(Ala-Ala), Teplizumab
* Drug: Placebo Arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 8 - 30, duration of diabetes 4 - 12 months, weight greater than 27.5 kg, stimulated C-peptide >= 0.2 pmol/ml Exclusion Criteria: asthma, history of hepatitis C, hepatitis B, HIV

Ages Eligible for Study
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Minimum Age: 8 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>The course of Teplizumab comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period. | Drug: mAb hOKT3gamma1(Ala-Ala), Teplizumab<br>* This is a randomized, two-arm, double blind placebo controlled phase II trial in which 60 participants with recent-onset T1DM are randomized at a 1:1 ratio to receive Teplizumab or placebo over a 14 day treatment period. The course of Teplizumab comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2.<br>* Other names: mAb hOKT3gamma1(Ala-Ala), MGA031, Teplizumab;|
| Placebo Comparator: 2<br>Normal saline infusion | Drug: Placebo Arm<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months | C-peptide secretory response was calculated as ln[(Area Under the Curve of the C-peptide from the 240 minute MMTT/240 +1] For presentation, the C-peptide data were converted to the AUC as pmol/ml. This is adjusted for baseline. | At month 12 post-treatment | 
| C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline | C-peptide secretory response was calculated as ln[(Area Under the Curve of the C-peptide from the 240 minute MMTT/240 +1] For presentation, the C-peptide data were converted to the AUC as pmol/ml. This baseline data was used to adjust for the C-peptide AUC primary endpoint measure at 12 months. | At Baseline (before treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin A1c |  | At 12 months post-treatment | 
| Average Insulin Use Over 12 Months |  | After 12 months post-treatment | 
| Baseline Insulin Use |  | At baseline (before treatment) | 
| Baseline Hemoglobin A1c |  | At baseline (before treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immune therapy, autoimmunity, insulin secretion, diabetes mellitus