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

Phase 3

Terminated

Interventions: Drug: Placebo
Biological: Teplizumab 33.3% Herold Regimen
Biological: Teplizumab Herold Regimen
Biological: Teplizumab Curtailed Herold Regimen

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	14-day cycle of placebo consisting of daily IV doses. Repeat at Week 26
33.3% Herold Regimen	Teplizumab 33.3% Herold Regimen	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
Herold Regimen	Teplizumab Herold Regimen	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
Curtailed Herold Regimen	Teplizumab Curtailed Herold Regimen	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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
The Mean HbA1c Change From Baseline	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
Mean Number of Total, Major, Minor and Nocturnal Hypoglycemia Events	Throughout the study up to 2 years	Number of hypoglycemic events by type per participant
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
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 Change in Beta-cell Function as Measured by C-peptide Secretory Response Following a Mixed Meal	104 weeks after randomization
Mean Number of Daily Insulin Injections	52 weeks after randomization

Locations (118): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
NEA Clinic
🇺🇸
Jonesboro, Arkansas, United States
Arkansas Children's Hospital
🇺🇸
Little Rock, Arkansas, United States
Clinical Innovations Inc. Research Facility
🇺🇸
Costa Mesa, California, United States
Axis Clinical Trials
🇺🇸
Los Angeles, California, United States
Diabetes Associates Medical Group, Inc
🇺🇸
Orange, California, United States
Clinical Innovations, Inc.
🇺🇸
Riverside, California, United States
San Diego Clinical Trials
🇺🇸
San Diego, California, United States
Ronald Chochinov Md Inc
🇺🇸
Ventura, California, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States