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

Sponsor
MacroGenics (Industry)
Overall Status
Completed
CT.gov ID
NCT00385697
Collaborator
Eli Lilly and Company (Industry)
554
Enrollment
115
Locations
4
Arms
58
Duration (Months)
4.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

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
Actual Enrollment :
554 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Care Provider)
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
Study Start Date :
Oct 1, 2006
Actual Primary Completion Date :
Jun 1, 2010
Actual Study Completion Date :
Aug 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1

Drug: Teplizumab
IV dosing daily for 14 days times 2 courses
Other Names:
  • MGA031

    		•
    Experimental: 2

    Drug: Teplizumab
    IV dosing daily for 14 days times 2 courses
    Other Names:
  • MGA031

    		•
    Experimental: 3

    Drug: Teplizumab
    IV dosing daily for 14 days times 2 courses
    Other Names:
  • MGA031

    		•
    Placebo Comparator: 4

    Other: Placebo
    IV dosing daily for 14 days times 2 courses

    Outcome Measures

    Primary Outcome Measures

    1. 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%. [at 12 months]

    2. The second primary endpoint is the mean HbA1c change from baseline at 52 weeks after randomization. [at 12 months]

    Secondary Outcome Measures

    1. Change from baseline in C-peptide AUC at 52 Weeks and 104 weeks after randomization. [at 24 months]

    2. 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% [at 24 months]

    3. 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%. [at 12 months]

    4. Mean HbA1c change from baseline at 104 weeks after randomization. [at 24 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    8 Years to 35 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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:

    6. islet-cell autoantibodies (ICA512/IA-2),

    7. glutamic acid decarboxylase autoantibodies, or

    8. insulin autoantibodies (if present during first 2 weeks, but not beyond 2 weeks, of insulin treatment)

    9. Male or female

    10. 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

    1. 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

    Locations

    Site City State Country Postal Code
    1 UAB School of Medicine Birmingham Alabama United States 35294
    2 NEA Clinic Jonesboro Arkansas United States 72401
    3 Arkansas Children's Hospital Little Rock Arkansas United States 72202
    4 Diabetes Medical Center of California Northridge California United States 91325
    5 UCSF Medical Center San Francisco California United States 94143
    6 University of Colorado Health Sciences Center Aurora Colorado United States 80045
    7 Yale University New Haven Connecticut United States 06519
    8 Christiana Care Research Institute Newark Delaware United States 19713
    9 Richard Hays, MD Wellington Florida United States 33414
    10 Atlanta Diabetes Associates Atlanta Georgia United States 30309
    11 Humphrey Diabetes Center Boise Idaho United States 87702
    12 Rocky Mountain Diabetes & Osteoporosis Center Idaho Falls Idaho United States 83404
    13 Riley Hospital for Children Indianapolis Indiana United States 46202
    14 University of Iowa Children's Hospital Iowa City Iowa United States 52242-1083
    15 Mid-America Diabetes Associates, PA Wichita Kansas United States 67211
    16 Commonwealth Biomedical Research, LLC Madisonville Kentucky United States 42431
    17 St. Agnes Hospital Baltimore Maryland United States 21229
    18 Maryland Diabetes & Endocrine Associates Rockville Maryland United States 20852
    19 Massachusetts General Hospital Boston Massachusetts United States 02114
    20 Baystate Medical Center Springfield Massachusetts United States 01199
    21 Alzohaili Medical Consultants Dearborn Michigan United States 48126
    22 The Children's Mercy Hospital Kansas City Missouri United States 64108
    23 Creighton Diabetes Center Omaha Nebraska United States 68131
    24 Saint Barnabas Medical Center Livingston New Jersey United States 07039
    25 University of Medicine & Dentistry of NJ New Brunswick New Jersey United States 08901
    26 Albany Medical Center Albany New York United States 12208
    27 Schneider Children's Hospital New Hyde Park New York United States 11040
    28 Joslin Diabetes Center Syracuse New York United States 13214
    29 Cleveland Clinic Cleveland Ohio United States 44195
    30 St. Mary Medical Center Langhorne Pennsylvania United States 19047
    31 Sumter Medical Specialists Sumter South Carolina United States 29150
    32 University Diabetes & Endocrine Consultants Chattanooga Tennessee United States 37403
    33 Methodist Healthcare Memphis Tennessee United States 38104
    34 Research Institute of Dallas Dallas Texas United States 75231
    35 Spectra Research Center McAllen Texas United States 78503
    36 Diabetes and Glandular Disease Research San Antonio Texas United States 78229
    37 Endocrine Research Specialists Ogden Utah United States 84403
    38 Pacific Northwest Research Institute Seattle Washington United States 98122
    39 Medical College of Wisconsin Milwaukee Wisconsin United States 53226
    40 Alberta Children's Hospital Calgary Alberta Canada T3B 6A8
    41 University of Manitoba Winnipeg Manitoba Canada R3E0Z2
    42 University Health Sciences Centre St. John's Newfoundland and Labrador Canada A1B3V6
    43 Capital District Health Authority Halifax Nova Scotia Canada B3H2YN
    44 Oxford AIM Clinic London Ontario Canada N6A 5R9
    45 Children's Hospital of Western London Ontario Canada N6A5W9
    46 FN Brno- Detska nemocnice Brno Czechia 62500
    47 FN Hradec Kralove Hradec Kralove Czechia 50005
    48 Nemocnice Jihlava Jihlava Czechia 58633
    49 FN Kralovske Vinohrady Praha 10 Czechia 10034
    50 Fakultni nemocnice v Motole Praha Czechia 150 06
    51 Masarykova nemocnice v Usti nad Labem Usti nad Labem Czechia 40113
    52 East Tallinn Central Hospital Ravi Tallinn Estonia 10138
    53 Tartu University Hospital Puusepa Tartu Estonia 51014
    54 Universitätsklinikum Heidelberg Heidelberg Baden-Wurttemberg Germany 69120
    55 Medizinische Universitätsklinik Ulm Ulm Baden-Wurttemberg Germany 89070
    56 Herz-und Diabetszentrum Nordrhein-Westfalen Bad Oeynhausen North Rhine-Westphalia Germany 32545
    57 Charité-Hochschulmedizin Berlin Berlin Germany 12200
    58 Universitatsklinik Giessen Giessen Germany 35392
    59 Nizam's Institute of Medical Sciences Hyderabad Andhra Pradesh India 500082
    60 King George Hospital Visakhapatnam Andhra Pradesh India 530002
    61 Gujarat Endocrine Centre Ahmedabad Gujarat India 380006
    62 DHL Research Centre Ahmedabad Gujarat India 380015
    63 Bharti Research Institute of Diabetes & Endocrinology Karnal Haryana India 132001
    64 Bangalore Diabetes Centre Bangalore Karnataka India 560043
    65 Diabetes Thyroid Hormone Research Institute PVT LTD Indore Madhya Pradesh India 452001
    66 Diabetes Action Centre Mumbai Maharashtra India 400067
    67 Gandhi Endocrinology and Diabetes Centre Nagpur Maharashtra India 440010
    68 Endocrine Clinic Nasik Maharashtra India 422013
    69 Grant Medical Foundation Pune Maharashtra India 411001
    70 Fortis Escorts Hospital Jaipur Rajasthan India 302017
    71 B.P.Poddar Hospital and Medical Research Ltd Kolkata West Bengal India 700053
    72 Medwin Hospitals Hyderabad India 500001
    73 Pushpawati Singhania Research Institute New Delhi India 110017
    74 Soroka Medical Centre Beer Sheba Israel 84101
    75 Hillel Yaffe Medical Center Hadera Israel 38100
    76 Rambam Medical Centre Haifa Israel 31096
    77 Wolfson Medical Centre Holon Israel 58100
    78 National Centre for Childhood and Diabetes Petach Tikva Israel 49202
    79 Chaim Sheba Medical Center Ramat-Gan Israel 56261
    80 P. Stradins Clinical University Hospital Riga Latvia 1002
    81 Hospital CIMA Santa Engracia San Pedro Garza García Nuevo Leon Mexico 66260
    82 Hospital Mexico-Americano Guadalajara Mexico 44620
    83 Hospital General de Mexico Mexico City Mexico 06726
    84 Hospital Central San Luis Potosí Mexico 78240
    85 Diabeter Center for Pediatric and Adolescent Diabetes Care and Research Rotterdam Netherlands 3011TG
    86 Samodzielny Publiczny Szpital Kliniczny Akademi Medycznej w Bialymstoku Bialystok Poland 15-276
    87 Oddzial Diabetologiczny Klinika Pediatrii Gdansk Poland 80-952
    88 Wojewodzki Specjalistyczny Szpital Dzieciecy Kielce Poland 25-734
    89 I. Szpital Miejski im. Dr. E. Sonnenberga w Lodzi Kodz Poland 92115
    90 Uniwersytecki Szpital Kliniczny Lodz Poland 91-738
    91 Powiatowy Zespot Szpitali w Olesnicy, Oddzial Chorob Wewnetrznych Olesnica Poland 56400
    92 Klinika Endokrynologii i Diabetologii Wieku Rozwojowego Wroclaw Poland 51-376
    93 S.C. Minimed S.R.L. Bacau Romania 600164
    94 Institutul de Diabet Bucharest Romania 020045
    95 Centrul Medical "Sanatatea ta" Bucuresti Romania 20725
    96 Spitulul Clinic Judetean de Urgenta Cluj Cluj-Napoca Romania 400006
    97 Spitalul Clinic Judetean de Urgenta Iasi Romania 700111
    98 Spitalul Judetean Satu Mare Satu Mare Romania 440055
    99 Hospital Universitari Dr. Josep Trueta de Girona Girona Gerona Spain 17007
    100 Hospital Universitario Principe de Asturias Alcala de Henares Madrid Spain 28805
    101 Hospital Germans Trias i Pujol Badalona Spain 8916
    102 Hospital Clinic I Provincial Barcelona Spain 8036
    103 Fundacion Jimenez Diaz Madrid Spain 28040
    104 Universitetssjukhuset i Linkoping Linkoping Sweden 58185
    105 Universitetssjukhuset i Lund Lund Sweden 22185
    106 Sodersjukhuset AB Stockholm Sweden 11883
    107 Donetsk Regional Children Clinical Hospital Donetsk Ukraine 83052
    108 V. Danilevsky Institute of Endocrine Pathology Problems Kharkiv Ukraine 61070
    109 Kharkiv Regional Clinical Children's Hospital Kharkiv Ukraine 61093
    110 Ukrainian Scientific and Practical Center of Endocrine Surgery Kyiv Ukraine 02175
    111 Ukranian Children Specialised Clinical Hospital Kyiv Ukraine 02175
    112 Regional Clinical Endocrinological Dispensary Vinnitsa Ukraine 21010
    113 Zaporizhzhya Regional Pediatric Hospital Zaporizhzhya Ukraine 69035
    114 Addenbrookes Hospital Cambridge Cambridgeshire United Kingdom CB20QQ
    115 Royal Devon and Exeter Hospital Exeter Devon United Kingdom EX25DW

    Sponsors and Collaborators

    • MacroGenics
    • Eli Lilly and Company

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    MacroGenics
    ClinicalTrials.gov Identifier:
    NCT00385697
    Other Study ID Numbers:
    • CP-MGA031-01
    First Posted:
    Oct 11, 2006
    Last Update Posted:
    Feb 8, 2022
    Last Verified:
    Jan 1, 2022
    Keywords provided by MacroGenics
    Randomized
    Double Blind
    Parallel Group
    Controlled Clinical Trial
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Diabetes Mellitus, Type 1

    Study Results

    No Results Posted as of Feb 8, 2022