A Phase 2/3, Randomized, Double-Blind, Multicenter, Multinational, 4-Arm, Controlled, Dose-Ranging Study to Evaluate Efficacy and Safety of MGA031, a Humanized, FcR Non-Binding, Anti-CD3 Monoclonal Antibody, in Children and Adults With Recent-Onset Type 1 Diabetes Mellitus
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- MacroGenics
- Enrollment
- 554
- Locations
- 115
- Primary Endpoint
- Number 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%.
Overview
Brief Summary
The primary purpose of this protocol is to assess the efficacy, tolerability, and safety of MGA031 when administered according to 3 different MGA031 dosing regimens in children and adults with recent-onset (diagnosis within past 12 weeks) type 1 diabetes mellitus. All regimens will be administered as an addition to insulin and other standard of care treatments. Efficacy will be defined primarily by the capacity of MGA031 to markedly reduce typical insulin requirements while maintaining relatively normal blood sugar levels.
Other studies involving the study drug use the name hOKT3γ1 (Ala-Ala). MGA031, a humanized monoclonal antibody, is the name used for hOKT3γ1 (Ala-Ala) that is produced by MacroGenics, Inc. The United States Adopted Name (USAN) for MGA031 is teplizumab.
Detailed Description
The Protégé Study - A Multinational Clinical Trial of MGA031 for Preserving the Capability to Produce Insulin, Reducing Insulin Usage and Improving Blood Sugar Levels in Children and Adults With Recent-Onset Type 1 Diabetes Mellitus
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- 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 must meet all of the following criteria:
- •Enrollment (Segment #1) or randomization (Segment #2) on Study Day 0 within 12 weeks of first visit to any physician for symptoms or signs of diabetes. Study Day 0 is the first day of study drug dosing.
- •Diagnosis of type 1 diabetes mellitus, according to the American Diabetes Association (ADA) criteria
- •Requirement for injected insulin therapy
- •Have a detectable fasting or stimulated C-peptide level (above the lower limit of detection of the assay)
- •One positive result on testing for any of the following antibodies:
- •islet-cell autoantibodies (ICA512/IA-2),
- •glutamic acid decarboxylase autoantibodies, or
- •insulin autoantibodies (if present during first 2 weeks, but not beyond 2 weeks, of insulin treatment)
- •Male or female
Exclusion Criteria
- •Subjects must have none of the following:
- •Prior administration of a monoclonal antibody -- within the 1 year before enrollment or randomization at Study Day 0 -- that could potentially prevent or confound a therapeutic response to MGA031
- •Participation in any type of therapeutic drug or vaccine clinical trial within the 12 weeks before enrollment or randomization
- •Any medical condition that, in the opinion of the investigator, would interfere with safe completion of the trial
- •Pregnant or lactating females
- •Prior murine OKT®3 treatment at any time before enrollment or randomization
- •Current or planned therapy with exenatide or any other agents that stimulate pancreatic beta cell regeneration or insulin secretion
- •Current or planned therapy with inhaled insulin
- •Uncompensated heart failure, fluid overload, myocardial infarction or evidence of ischemic heart disease, or other serious cardiac disease within the 12 weeks before enrollment or randomization
- •History of epilepsy, cancer, cystic fibrosis, sickle cell anemia, neuropathy, peripheral vascular disease or cerebrovascular disease
Arms & Interventions
Double-blind Curtailed Herold Regimen
Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26
Intervention: Teplizumab (Biological)
Double-blind Herold Regimen
Full dose of teplizumab IV for 14 days, repeated at Week 26
Intervention: Teplizumab (Biological)
Double-blind 33.3% Herold Regimen
One third full dose of teplizumab IV for 14 days, repeated at Week 26
Intervention: Teplizumab (Biological)
Double-blind Placebo
Placebo IV dosing daily for 14 days repeated at Week 26
Intervention: Placebo (Drug)
Open-label Herold Regimen
Full dose of teplizumab IV for 14 days, repeated at Week 26
Intervention: Teplizumab (Biological)
Outcomes
Primary Outcomes
Number 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%.
Time Frame: 52 weeks after randomization
This is a composite endpoint is based on the proportion of subjects who have both a total daily insulin dose \<0.5 U/Kg/day and an HbAlc level 6.5% at 52 weeks after randomization.
Number of Subjects in Segment 1 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 first dose
This is a composite endpoint based on the proportion of subjects who have both a total daily insulin dose \<0.5 U/Kg/day and an HbAlc level 6.5%
Mean HbA1c Change From Baseline in Segment 2
Time Frame: 52 weeks after randomization
Comparison among study treatments of average change from baseline HbA1C. This endpoint will be assessed in a hierarchical manner only if the composite primary endpoint shows a statistically significant difference between arms
Mean HbA1c Change From Baseline in Segment 1
Time Frame: 52 weeks after first dose
The average change in HbA1c levels after dosing.
Secondary Outcomes
- Change From Baseline in C-peptide Area Under the Curve (AUC) in Segment 2(104 weeks after randomization)
- Change From Baseline in C-peptide AUC in Segment 1(104 weeks after first dose)
- Number of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and HbA1c Level of Less Than 6.5%(104 weeks after randomization)
- Number of Subjects in Segment 1 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and HbA1c Level of Less Than 6.5%(104 weeks after first dose)
- Number of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and HbA1c Level of Less Than 7.0%.(at 52 weeks after randomization)
- Number of Subjects in Segment 1 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and HbA1c Level of Less Than 7.0%.(52 weeks after first dose)
- Mean HbA1c Change From Baseline in Segment 2(at 104 weeks after randomization)
- Mean HbA1c Change From Baseline in Segment 1(104 weeks after first dose)