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

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
MacroGenics
ClinicalTrials.gov Identifier:
NCT00385697
First received: October 7, 2006
Last updated: August 21, 2012
Last verified: August 2012
  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 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by MacroGenics:

Primary Outcome Measures:
  • The first primary endpoint is a composite endpoint at 52 weeks: the proportion of subjects with both a total daily insulin dose of less than 0.5 U/kg/day and HbA1c level of less than 6.5%. [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]
  • The second primary endpoint is the mean HbA1c change from baseline at 52 weeks after randomization. [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change from baseline in C-peptide AUC at 52 Weeks and 104 weeks after randomization. [ Time Frame: at 24 months ] [ Designated as safety issue: Yes ]
  • The proportion of subjects at 104 weeks after randomization, that have both a total daily insulin dose of less than 0.5 U/kg/day and HbA1c level of less than 6.5% [ Time Frame: at 24 months ] [ Designated as safety issue: Yes ]
  • The proportion of subjects at 52 weeks after randomization, that have both a total daily insulin dose of less than 0.5 U/kg/day and HbA1c level of less than 7.0%. [ Time Frame: at 12 months ] [ Designated as safety issue: Yes ]
  • Mean HbA1c change from baseline at 104 weeks after randomization. [ Time Frame: at 24 months ] [ Designated as safety issue: Yes ]

Enrollment: 554
Study Start Date: October 2006
Study Completion Date: August 2011
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Teplizumab
IV dosing daily for 14 days times 2 courses
Other Name: MGA031
Experimental: 2 Drug: Teplizumab
IV dosing daily for 14 days times 2 courses
Other Name: MGA031
Experimental: 3 Drug: Teplizumab
IV dosing daily for 14 days times 2 courses
Other Name: MGA031
Placebo Comparator: 4 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:

  1. 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.
  2. Diagnosis of type 1 diabetes mellitus, according to the American Diabetes Association (ADA) criteria
  3. Requirement for injected insulin therapy
  4. Have a detectable fasting or stimulated C-peptide level (above the lower limit of detection of the assay)
  5. 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)
  6. Male or female
  7. 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
  8. Body weight ≥ 36 kg

Exclusion Criteria:

Subjects must have none of the following:

  1. 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
  2. Participation in any type of therapeutic drug or vaccine clinical trial within the 12 weeks before enrollment or randomization
  3. Any medical condition that, in the opinion of the investigator, would interfere with safe completion of the trial
  4. Pregnant or lactating females
  5. Prior murine OKT®3 treatment at any time before enrollment or randomization
  6. Current or planned therapy with exenatide or any other agents that stimulate pancreatic beta cell regeneration or insulin secretion
  7. Current or planned therapy with inhaled insulin
  8. 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
  9. History of epilepsy, cancer, cystic fibrosis, sickle cell anemia, neuropathy, peripheral vascular disease or cerebrovascular disease
  10. Newly diagnosed hypothyroidism (not currently being treated but which, in the opinion of the investigator, should be treated) or active Graves' disease
  11. Eczema, asthma or severe atopic disease requiring treatment within the 12 weeks before enrollment or randomization
  12. Evidence of active infection, such as fever ≥ 38.0 degrees Celsius (100.5 degrees Fahrenheit)
  13. Known or suspected infection with human immunodeficiency virus (HIV)
  14. Evidence of active hepatitis B (HBV) or hepatitis C virus (HCV)
  15. Evidence of active or latent tuberculosis
  16. 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.
  17. Any infectious mononucleosis-like illness within the 6 months before enrollment or randomization
  18. Serologic and clinical evidence of acute infection with Epstein-Barr virus (EBV)
  19. Serologic evidence of acute infection with cytomegalovirus (CMV)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00385697

  Show 115 Study Locations
Sponsors and Collaborators
MacroGenics
Eli Lilly and Company
  More Information

No publications provided by MacroGenics

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT00385697     History of Changes
Other Study ID Numbers: CP-MGA031-01
Study First Received: October 7, 2006
Last Updated: August 21, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by MacroGenics:
Randomized
Double Blind
Parallel Group
Controlled Clinical Trial

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 14, 2014