The Protégé Study - Clinical Trial of MGA031 in Children and Adults With Recent-Onset Type 1 Diabetes Mellitus - Full Text View

Sponsors and Collaborators:	MacroGenics Juvenile Diabetes Research Foundation
Information provided by:	MacroGenics
ClinicalTrials.gov Identifier:	NCT00385697

Purpose

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.

Condition	Intervention	Phase
Type 1 Diabetes Mellitus	Drug: Teplizumab Other: Placebo	Phase II Phase III

MedlinePlus related topics: Diabetes Diabetes Type 1

Drug Information available for: Immunoglobulins Globulin, Immune Visilizumab

U.S. FDA Resources

Study Type:

Interventional

Study Design:

Treatment, Randomized, Double Blind (Subject, Caregiver), Active Control, Parallel Assignment, Efficacy Study

Official Title:

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

Further study details as provided by MacroGenics:

Primary Outcome Measures:

Successful versus unsuccessful clinical responses. A successful response requires that both components of a composite endpoint are met. The composite endpoint includes both the subject's total daily insulin usage and his/her HbA1c levels. [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Successful versus unsuccessful clinical responses. A successful response requires that both components of a composite endpoint are met. The composite endpoint includes both the subject's total daily insulin usage and his/her HbA1c levels. [ Time Frame: at 24 months ] [ Designated as safety issue: Yes ]
C-peptide secretory responses, as defined by the total area under the curve of the C-peptide response to a mixed meal [ Time Frame: at 24 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:

530

Study Start Date:

October 2006

Estimated Study Completion Date:

March 2011

Estimated Primary Completion Date:

March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: Teplizumab IV dosing daily for 14 days times 2 courses
2: Experimental	Drug: Teplizumab IV dosing daily for 14 days times 2 courses
3: Experimental	Drug: Teplizumab IV dosing daily for 14 days times 2 courses
4: Placebo Comparator	Other: Placebo IV dosing daily for 14 days times 2 courses

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

Eligibility

Ages Eligible for Study:

8 Years to 35 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

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:
1. islet-cell autoantibodies (ICA512/IA-2),
2. glutamic acid decarboxylase autoantibodies, or
3. insulin autoantibodies (if present during first 2 weeks, but not beyond 2 weeks, of insulin treatment)
Male or female
Subject must be in one of the following age groups:
- Age 18-35 years
- Age 12-17 years pending approval by Data Monitoring Committee
- Age 8-11 years pending approval by Data Monitoring Committee
Body weight ≥ 36 kg

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
Newly diagnosed hypothyroidism (not currently being treated but which, in the opinion of the investigator, should be treated) or active Graves' disease
Eczema, asthma or severe atopic disease requiring treatment within the 12 weeks before enrollment or randomization
Evidence of active infection, such as fever ≥ 38.0 degrees Celsius (100.5 degrees Fahrenheit)
Known or suspected infection with human immunodeficiency virus (HIV)
Evidence of active hepatitis B (HBV) or hepatitis C virus (HCV)
Evidence of active or latent tuberculosis
Vaccination with a live virus within the 12 weeks before enrollment or randomization or planned live virus vaccination continuing through week 52 of the study. Vaccination with an antigen or killed organism must not be given within 12 weeks before or planned within 8 weeks after each dosing cycle.
Any infectious mononucleosis-like illness within the 6 months before enrollment or randomization
Serologic and clinical evidence of acute infection with Epstein-Barr virus (EBV)
Serologic evidence of acute infection with cytomegalovirus (CMV)