Protege Encore Study- Clinical Trial of Teplizumab (MGA031) in Children and Adults With Recent-Onset Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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The primary purpose of this study is to determine whether teplizumab (MGA031) infusions lead to greater reductions in insulin requirements in conjunction with near normal blood sugar control compared to placebo in patients recently diagnosed with type 1 diabetes.

Official Title
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A Phase 3, Randomized, Double-Blind, Multinational, Placebo-Controlled Study to Evaluate Efficacy and Safety of Teplizumab (MGA031), a Humanized, FcR Non-Binding, Anti-CD3 Monoclonal Antibody, in Children and Adults With Recent-Onset Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Biological: Teplizumab Herold Regimen
* Drug: Placebo
* Biological: Teplizumab 33.3% Herold Regimen
* Biological: Teplizumab Curtailed Herold Regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects 8-35 years old Body weight > 36 Kg Diagnosis of diabetes mellitus according to the American Diabetes Association (ADA) criteria Randomization on Study Day 0 within 12 weeks of first visit to any physician for symptoms or signs of diabetes Requires insulin for T1DM or has required insulin at some time between diagnosis and administration of study drug Detectable fasting or stimulated C-peptide level (above the lower limit of the reportable range of the assay) at screening Diagnosis of T1DM as evidenced by one positive result on testing for any of the following antibodies at screening: Islet-cell autoantibodies 512 (ICA512)/islet antigen-2 (IA-2), Glutamic acid decarboxylase (GAD) autoantibodies, or Insulin autoantibodies (in subjects on insulin for more than 2 weeks, ICA512/IA-2 or GAD must be positive). Exclusion Criteria: Prior administration of a monoclonal antibody-within the 1 year before randomization Participation in any type of therapeutic drug or vaccine clinical trial within the last 12 weeks before randomization at Study Day 0 Any medical condition that, in the opinion of the investigator, would interfere with safe completion of the trial Pregnant females or lactating females who intend to provide their own breast milk to the baby during the study Current therapy with GLP-1 receptor agonists (e.g., exenatide or pramlintide), or any other agents that might stimulate pancreatic beta cell regeneration or insulin secretion Current treatment with oral antidiabetic agents Evidence of active or latent tuberculosis Vaccination with a live virus or organism within the 8 weeks before randomization continuing through Week 52 of the study. Influenza vaccination with a killed virus, including booster vaccinations, within 4 weeks before or after each dosing cycle. Vaccination with other antigens or killed organisms within 8 weeks before or after each dosing cycle Any infectious mononucleosis-like illness within the 6 months before randomization

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 35 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: Herold Regimen<br>14-day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-14. Repeat at Week 26 | Biological: Teplizumab Herold Regimen<br>* Full dose of teplizumab IV for 14 days, repeated at Week 26<br>* Other names: MGA031;|
| Experimental: 33.3% Herold Regimen<br>Subjects received a 14-day cycle of teplizumab consisting of daily IV doses of 17 µg/m2, 34 µg/m2, 68 µg/m2, and 136 µg/m2 on Study Days 1-4, respectively, and one dose of 273 µg/m2 on each of Study Days 5-14. Repeat at Week 26 | Biological: Teplizumab 33.3% Herold Regimen<br>* One third full dose of teplizumab IV for 14 days, repeated at Week 26<br>* Other names: MGA031;|
| Experimental: Curtailed Herold Regimen<br>Subjects received a 6 day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-6, followed by 8 days of IV placebo (Study Days 7-14). Repeat at Week 26 | Biological: Teplizumab Curtailed Herold Regimen<br>* Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26<br>|
| Placebo Comparator: Placebo<br>14-day cycle of placebo consisting of daily IV doses. Repeat at Week 26 | Drug: Placebo<br>* IV dosing daily for 14 days repeated at Week 26<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects 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%. |  | 52 weeks after randomization | 
| Mean Change From Baseline in HbA1c Between Teplizumab and Placebo |  | 52 weeks after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change in Beta-cell Function as Measured by C-peptide Secretory Response Following a Mixed Meal |  | 52 weeks after randomization | 
| The Change in Beta-cell Function as Measured by C-peptide Secretory Response Following a Mixed Meal |  | 104 weeks after randomization | 
| Mean Number of Total, Major, Minor and Nocturnal Hypoglycemia Events | Number of hypoglycemic events by type per participant | Throughout the study up to 2 years | 
| Mean Number of Daily Insulin Injections |  | 52 weeks after randomization | 
| Number of Subjects 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%. |  | 104 weeks after randomization | 
| The Proportion of Subjects Who Have Both a Total Daily Insulin Dose < 0.5 U/Kg/Day and Hemoglobin A1c (HbA1c) Level < 7.0% |  | 52 weeks after randomization | 
| The Mean HbA1c Change From Baseline |  | 104 weeks after randomization | 
| Number of Participants With Adverse Events |  | throughout the study, up to 104 weeks | 
| Number of Participants With Serious Adverse Events |  | throughout the study, up to 104 weeks |