Protege Extension Trial - Long Term Follow Up Trial for Subjects Who Completed the Protege Study (CP-MGA031-01)

Study Overview
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Brief Summary
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The purpose of this study is to assess the long term safety and efficacy in subjects with Type 1 Diabetes Mellitus who completed the Protege Study (CP-MGA031-01).

Detailed Description
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The primary objective of the extension study is to assess long-term safety, with particular focus on the development of serious adverse events (SAEs), adverse events of special interest (AESIs) including opportunistic infections and lymphoproliferative disease, and other immediately reportable events (IREs), in subjects with recent-onset T1DM who complete CP-MGA031-01. The secondary objectives of the extension study are to: 1) assess long-term efficacy; 2) evaluate immunological effects(North America only); 3) measure anti-teplizumab antibody levels;4) assess Health Related Quality of Life Questionnaires.

Official Title
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An Extension of Study CP-MGA031-01 to Evaluate the Long-Term Efficacy and Safety of Teplizumab (MGA031), a Humanized, FcR Non-Binding, Anti-CD3 Monoclonal Antibody, in Patients With Recent-Onset Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Diagnostic Test: Blood samples for safety
* Behavioral: Patient reported outcome questionnaires
* Diagnostic Test: Analysis of T-cell subsets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Complete Protocol CP-MGA031-01 (i.e., all subjects who complete Study Day 728, regardless of how many doses of study drug are received). Provide written informed consent. Exclusion Criteria: None

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 37 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: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Double-blind Herold Regimen<br>Patients who had been assigned to Herold Regimen in Segment 2 of Study CP-MGA031-01 were enrolled to gather additional safety and efficacy data. | Diagnostic Test: Blood samples for safety<br>* serum chemistry, hematology, infection screen, thyroid function, Insulin, hemoglobin A1c,and autoantibodies<br>Behavioral: Patient reported outcome questionnaires<br>* EQ-5D, Peds QL, Low blood sugar survey, and hospitalization information.<br>Diagnostic Test: Analysis of T-cell subsets<br>* CD3, CD4, CD8, CD19, CD3+ CD16+ CD56+ subsets; CD3-CD16+ CD56+ subsets; CD4+CD25+, CD8+CD25+, CD4+CD69+, CD8+CD69+, CD4+CD40+ subsets CD4+ and CD8+CD25+FoxP3+Treg Subsets<br>|
| Experimental: Double-blind 33.3% Herold Regimen<br>Patients who had been assigned to 33.3% Herold Regimen in Segment 2 of Study CP-MGA031-01 were enrolled to gather additional safety and efficacy data. | Diagnostic Test: Blood samples for safety<br>* serum chemistry, hematology, infection screen, thyroid function, Insulin, hemoglobin A1c,and autoantibodies<br>Behavioral: Patient reported outcome questionnaires<br>* EQ-5D, Peds QL, Low blood sugar survey, and hospitalization information.<br>Diagnostic Test: Analysis of T-cell subsets<br>* CD3, CD4, CD8, CD19, CD3+ CD16+ CD56+ subsets; CD3-CD16+ CD56+ subsets; CD4+CD25+, CD8+CD25+, CD4+CD69+, CD8+CD69+, CD4+CD40+ subsets CD4+ and CD8+CD25+FoxP3+Treg Subsets<br>|
| Experimental: Double-blind Curtailed Herold Regimen<br>Patients who had been assigned to Curtailed Herold Regimen in Segment 2 of Study CP-MGA031-01 were enrolled to gather additional safety and efficacy data. | Diagnostic Test: Blood samples for safety<br>* serum chemistry, hematology, infection screen, thyroid function, Insulin, hemoglobin A1c,and autoantibodies<br>Behavioral: Patient reported outcome questionnaires<br>* EQ-5D, Peds QL, Low blood sugar survey, and hospitalization information.<br>Diagnostic Test: Analysis of T-cell subsets<br>* CD3, CD4, CD8, CD19, CD3+ CD16+ CD56+ subsets; CD3-CD16+ CD56+ subsets; CD4+CD25+, CD8+CD25+, CD4+CD69+, CD8+CD69+, CD4+CD40+ subsets CD4+ and CD8+CD25+FoxP3+Treg Subsets<br>|
| Placebo Comparator: Double-blind Placebo<br>Patients who had been assigned to Placebo in Segment 2 of Study CP-MGA031-01 were enrolled to gather additional safety and efficacy data. | Diagnostic Test: Blood samples for safety<br>* serum chemistry, hematology, infection screen, thyroid function, Insulin, hemoglobin A1c,and autoantibodies<br>Behavioral: Patient reported outcome questionnaires<br>* EQ-5D, Peds QL, Low blood sugar survey, and hospitalization information.<br>Diagnostic Test: Analysis of T-cell subsets<br>* CD3, CD4, CD8, CD19, CD3+ CD16+ CD56+ subsets; CD3-CD16+ CD56+ subsets; CD4+CD25+, CD8+CD25+, CD4+CD69+, CD8+CD69+, CD4+CD40+ subsets CD4+ and CD8+CD25+FoxP3+Treg Subsets<br>|
| Experimental: Open-label Herold Regimen<br>Patients who had been assigned to Herold Regimen in Segment 1 of Study CP-MGA031-01 were enrolled to gather additional safety and efficacy data. | Diagnostic Test: Blood samples for safety<br>* serum chemistry, hematology, infection screen, thyroid function, Insulin, hemoglobin A1c,and autoantibodies<br>Behavioral: Patient reported outcome questionnaires<br>* EQ-5D, Peds QL, Low blood sugar survey, and hospitalization information.<br>Diagnostic Test: Analysis of T-cell subsets<br>* CD3, CD4, CD8, CD19, CD3+ CD16+ CD56+ subsets; CD3-CD16+ CD56+ subsets; CD4+CD25+, CD8+CD25+, CD4+CD69+, CD8+CD69+, CD4+CD40+ subsets CD4+ and CD8+CD25+FoxP3+Treg Subsets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants Who Experience an Adverse Event, Serious Adverse Event or Adverse Event of Special Interest. |  | Duration of study participation up to 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%. |  | Month 6 | 
| Proportion of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%. |  | Month 12 | 
| Proportion of Subjects With HbA1c <6.5% |  | Month 6 | 
| Mean HbA1c at 6 Months |  | 6 months | 
| Mean HbA1c at 12 Months |  | Month 12 | 
| C-peptide Area Under the Curve (AUC) at 6 Months | This outcome measure summarizes the mean and standard deviation of the observed value. | Month 6 | 
| C-peptide AUC at 12 Months | This outcome measure summarizes the mean and standard deviation of the observed value. | Month 12 | 
| Total Daily Insulin Usage at 6 Months |  | Month 6 | 
| Total Daily Insulin Usage at 12 Months |  | Month 12 | 
| Mean Values for Participant-reported Outcomes on the 5-dimension European Quality of Life Questionnaire. (EQ-5D) | The EQ-5D is a self-reported survey that measures quality of life across 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on a 3-level severity ranking that ranges from no problems, some problems, and extreme problems. The lowest possible score is 5 and the highest possible score is 15. Lower scores indicate better quality of life. | Month 6 | 
| Mean Values for Participant-reported Outcomes on the EQ-5D | The EQ-5D is a self-reported survey that measures quality of life across 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on a 3-level severity ranking that ranges from no problems, some problems, and extreme problems. The lowest possible score is 5 and the highest possible score is 15. Lower scores indicate better quality of life. | Month 12 | 
| Pediatric Quality of Life Questionnaire Total Score | The 23-item PEDs QL generic core scales were designed to measure the core dimensions of health (physical, emotional, social and school functioning). Answers are scored from 0 meaning never to 4 meaning almost always. Lower scores indicated higher quality of life. Items on the questionnaire were reversely scored and linearly transformed to a 0-100 scale, so that higher scores indicated better patient reported outcome. The mean was computed as the sum of the items over the number of items answered (to account for missing data). If more than 50% of the items in the scale were missing, the score was not computed. | Month 6 | 
| Pediatric Quality of Life Questionnaire Total Score | The 23-item PEDs QL generic core scales were designed to measure the core dimensions of health (physical, emotional, social and school functioning). Answers are scored from 0 meaning never to 4 meaning almost always. Lower scores indicated higher quality of life. Items on the questionnaire were reversely scored and linearly transformed to a 0-100 scale, so that higher scores indicated better patient reported outcome. The mean was computed as the sum of the items over the number of items answered (to account for missing data). If more than 50% of the items in the scale were missing, the score was not computed. | Month 12 | 
| Percentage of Cells by Immunophenotype |  | Month 6 | 
| Human Anti-human Antibody (HAHA) Levels | Patients with HAHA levels > 0. | Month 6 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MGA031, T1DM, Teplizumab, Protege, Monoclonal antibody, Type 1 Diabetes Mellitus, MacroGenics