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
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- MacroGenics
- Enrollment
- 254
- Locations
- 118
- Primary Endpoint
- 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%.
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 8 Years to 35 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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
Intervention: Teplizumab Herold Regimen (Biological)
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
Intervention: Teplizumab 33.3% Herold Regimen (Biological)
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
Intervention: Teplizumab Curtailed Herold Regimen (Biological)
Placebo
14-day cycle of placebo consisting of daily IV doses. Repeat at Week 26
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
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%.
Time Frame: 52 weeks after randomization
Mean Change From Baseline in HbA1c Between Teplizumab and Placebo
Time Frame: 52 weeks after randomization
Secondary Outcomes
- The Mean HbA1c Change From Baseline(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)
- 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 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)
- 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)