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

October 7, 2006
August 21, 2012
October 2006
June 2010   (final data collection date for primary outcome measure)
  • 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 ]
Successful versus unsuccessful clinical responses at 12 months. 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.
Complete list of historical versions of study NCT00385697 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Successful versus unsuccessful clinical responses at 24 months. A successful response requires that both components of a composite endpoint are met. The composite endpoint includes both the subjects’s total daily insulin usage and his/her HbA1c levels.
  • C-peptide secretory responses at 24 months, as defined by the total area under the curve of the C-peptide response to a mixed meal.
Not Provided
Not Provided
 
The Protégé Study - Clinical Trial of MGA031 in Children and Adults With Recent-Onset Type 1 Diabetes Mellitus
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

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.

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

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Type 1 Diabetes Mellitus
  • Drug: Teplizumab
    IV dosing daily for 14 days times 2 courses
    Other Name: MGA031
  • Other: Placebo
    IV dosing daily for 14 days times 2 courses
  • Experimental: 1
    Intervention: Drug: Teplizumab
  • Experimental: 2
    Intervention: Drug: Teplizumab
  • Experimental: 3
    Intervention: Drug: Teplizumab
  • Placebo Comparator: 4
    Intervention: Other: Placebo
Sherry N, Hagopian W, Ludvigsson J, Jain SM, Wahlen J, Ferry RJ Jr, Bode B, Aronoff S, Holland C, Carlin D, King KL, Wilder RL, Pillemer S, Bonvini E, Johnson S, Stein KE, Koenig S, Herold KC, Daifotis AG; Protégé Trial Investigators. Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomised, placebo-controlled trial. Lancet. 2011 Aug 6;378(9790):487-97. Epub 2011 Jun 28.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
554
August 2011
June 2010   (final data collection date for primary outcome measure)

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)
Both
8 Years to 35 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   Czech Republic,   Estonia,   Germany,   India,   Israel,   Latvia,   Mexico,   Netherlands,   Poland,   Romania,   Spain,   Sweden,   Ukraine,   United Kingdom
 
NCT00385697
CP-MGA031-01
Yes
MacroGenics
MacroGenics
Eli Lilly and Company
Not Provided
MacroGenics
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP