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

MacroGenics

Status and phase: Terminated; Phase 3

Conditions: Type 1 Diabetes Mellitus

Treatments: Biological: Teplizumab Curtailed Herold Regimen; Biological: Teplizumab 33.3% Herold Regimen; Drug: Placebo; Biological: Teplizumab Herold Regimen

Study type: Interventional

Funder types: Industry

Identifiers

NCT00920582

CP-MGA031-03

Details and patient eligibility

About

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.

Enrollment: 254 patients

Sex: All

Ages: 8 to 35 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Subjects 8-35 years old

2. Body weight > 36 Kg

3. Diagnosis of diabetes mellitus according to the American Diabetes Association (ADA) criteria

4. Randomization on Study Day 0 within 12 weeks of first visit to any physician for symptoms or signs of diabetes

5. Requires insulin for T1DM or has required insulin at some time between diagnosis and administration of study drug

6. Detectable fasting or stimulated C-peptide level (above the lower limit of the reportable range of the assay) at screening

7. 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

1. Prior administration of a monoclonal antibody-within the 1 year before randomization

2. Participation in any type of therapeutic drug or vaccine clinical trial within the last 12 weeks before randomization at Study Day 0

3. Any medical condition that, in the opinion of the investigator, would interfere with safe completion of the trial

4. Pregnant females or lactating females who intend to provide their own breast milk to the baby during the study

5. 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

6. Current treatment with oral antidiabetic agents

7. Evidence of active or latent tuberculosis

8. 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

9. Any infectious mononucleosis-like illness within the 6 months before randomization

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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254 participants in 4 patient groups, including a placebo group

Herold Regimen

Experimental group

Description:

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

Treatment:

Biological: Teplizumab Herold Regimen

33.3% Herold Regimen

Experimental group

Description:

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

Treatment:

Biological: Teplizumab 33.3% Herold Regimen

Curtailed Herold Regimen

Experimental group

Description:

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

Treatment:

Biological: Teplizumab Curtailed Herold Regimen

Placebo

Placebo Comparator group

Description:

14-day cycle of placebo consisting of daily IV doses. Repeat at Week 26

Treatment:

Drug: Placebo