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

  Hide Study Locations
Locations
United States, Alabama
UAB School of Medicine
Birmingham, Alabama, United States, 35294
United States, Arkansas
NEA Clinic
Jonesboro, Arkansas, United States, 72401
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202
United States, California
Diabetes Medical Center of California
Northridge, California, United States, 91325
UCSF Medical Center
San Francisco, California, United States, 94143
United States, Colorado
University of Colorado Health Sciences Center
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06519
United States, Delaware
Christiana Care Research Institute
Newark, Delaware, United States, 19713
United States, Florida
Richard Hays, MD
Wellington, Florida, United States, 33414
United States, Georgia
Atlanta Diabetes Associates
Atlanta, Georgia, United States, 30309
United States, Idaho
Humphrey Diabetes Center
Boise, Idaho, United States, 87702
Rocky Mountain Diabetes & Osteoporosis Center
Idaho Falls, Idaho, United States, 83404
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa Children's Hospital
Iowa City, Iowa, United States, 52242-1083
United States, Kansas
Mid-America Diabetes Associates, PA
Wichita, Kansas, United States, 67211
United States, Kentucky
Commonwealth Biomedical Research, LLC
Madisonville, Kentucky, United States, 42431
United States, Maryland
St. Agnes Hospital
Baltimore, Maryland, United States, 21229
Maryland Diabetes & Endocrine Associates
Rockville, Maryland, United States, 20852
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Baystate Medical Center
Springfield, Massachusetts, United States, 01199
United States, Michigan
Alzohaili Medical Consultants
Dearborne, Michigan, United States, 48126
United States, Missouri
The Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
United States, Nebraska
Creighton Diabetes Center
Omaha, Nebraska, United States, 68131
United States, New Jersey
Saint Barnabas Medical Center
Livingston, New Jersey, United States, 07039
University of Medicine & Dentistry of NJ
New Brunswick, New Jersey, United States, 08901
United States, New York
Albany Medical Center
Albany, New York, United States, 12208
Schneider Children's Hospital
New Hyde Park, New York, United States, 11040
Joslin Diabetes Center
Syracuse, New York, United States, 13214
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
St. Mary Medical Center
Langhorne, Pennsylvania, United States, 19047
United States, South Carolina
Sumter Medical Specialists
Sumter, South Carolina, United States, 29150
United States, Tennessee
University Diabetes & Endocrine Consultants
Chattanooga, Tennessee, United States, 37403
Methodist Healthcare
Memphis, Tennessee, United States, 38104
United States, Texas
Research Institute of Dallas
Dallas, Texas, United States, 75231
Spectra Research Center
McAllen, Texas, United States, 78503
Diabetes and Glandular Disease Research
San Antonio, Texas, United States, 78229
United States, Utah
Endocrine Research Specialists
Ogden, Utah, United States, 84403
United States, Washington
Pacific Northwest Research Institute
Seattle, Washington, United States, 98122
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada, T3B 6A8
Canada, Manitoba
University of Manitoba
Winnipeg, Manitoba, Canada, R3E0Z2
Canada, Newfoundland and Labrador
University Health Sciences Centre
St. John's, Newfoundland and Labrador, Canada, A1B3V6
Canada, Nova Scotia
Capital District Health Authority
Halifax, Nova Scotia, Canada, B3H2YN
Canada, Ontario
Oxford AIM Clinic
London, Ontario, Canada, N6A 5R9
Children's Hospital of Western
London, Ontario, Canada, N6A5W9
Czech Republic
FN Brno- Detska nemocnice
Brno, Czech Republic, 62500
FN Hradec Kralove
Hradec Kralove, Czech Republic, 50005
Nemocnice Jihlava
Jihlava, Czech Republic, 58633
Fakultni nemocnice v Motole
Praha, Czech Republic, 150 06
FN Kralovske Vinohrady
Praha 10, Czech Republic, 10034
Masarykova nemocnice v Usti nad Labem
Usti nad Labem, Czech Republic, 40113
Estonia
East Tallinn Central Hospital
Ravi, Tallinn, Estonia, 10138
Tartu University Hospital
Puusepa, Tartu, Estonia, 51014
Germany
Universitätsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, Germany, 69120
Medizinische Universitätsklinik Ulm
Ulm, Baden-Wurttemberg, Germany, 89070
Herz-und Diabetszentrum Nordrhein-Westfalen
Bad Oeynhausen, North Rhine-Westphalia, Germany, 32545
Charité-Hochschulmedizin Berlin
Berlin, Germany, 12200
Universitatsklinik Giessen
Giessen, Germany, 35392
India
Nizam's Institute of Medical Sciences
Hyderabad, Andhra Pradesh, India, 500082
King George Hospital
Visakhapatnam, Andhra Pradesh, India, 530002
DHL Research Centre
Ahmedabad, Gujarat, India, 380015
Gujarat Endocrine Centre
Ahmedabad, Gujarat, India, 380006
Bharti Research Institute of Diabetes & Endocrinology
Karnal, Haryana, India, 132001
Bangalore Diabetes Centre
Bangalore, Karnataka, India, 560043
Diabetes Thyroid Hormone Research Institute PVT LTD
Indore, Madhya Pradesh, India, 452001
Diabetes Action Centre
Mumbai, Maharashtra, India, 400067
Gandhi Endocrinology and Diabetes Centre
Nagpur, Maharashtra, India, 440010
Endocrine Clinic
Nasik, Maharashtra, India, 422013
Grant Medical Foundation
Pune, Maharashtra, India, 411001
Fortis Escorts Hospital
Jaipur, Rajasthan, India, 302017
B.P.Poddar Hospital and Medical Research Ltd
Kolkata, West Bengal, India, 700053
Medwin Hospitals
Hyderabad, India, 500001
Pushpawati Singhania Research Institute
New Delhi, India, 110017
Israel
Soroka Medical Centre
Beer Sheba, Israel, 84101
Hillel Yaffe Medical Center
Hadera, Israel, 38100
Rambam Medical Centre
Haifa, Israel, 31096
Wolfson Medical Centre
Holon, Israel, 58100
National Centre for Childhood and Diabetes
Petach Tikva, Israel, 49202
Chaim Sheba Medical Center
Ramat-Gan, Israel, 56261
Latvia
P. Stradins Clinical University Hospital
Riga, Latvia, 1002
Mexico
Hospital CIMA Santa Engracia
San Pedro Garza García, Nuevo Leon, Mexico, 66260
Hospital Mexico-Americano
Guadalajara, Mexico, 44620
Hospital General de Mexico
Mexico City, Mexico, 06726
Hospital Central
San Luis Potosí, Mexico, 78240
Netherlands
Diabeter Center for Pediatric and Adolescent Diabetes Care and Research
Rotterdam, Netherlands, 3011TG
Poland
Samodzielny Publiczny Szpital Kliniczny Akademi Medycznej w Bialymstoku
Bialystok, Poland, 15-276
Oddzial Diabetologiczny Klinika Pediatrii
Gdansk, Poland, 80-952
Wojewodzki Specjalistyczny Szpital Dzieciecy
Kielce, Poland, 25-734
I. Szpital Miejski im. Dr. E. Sonnenberga w Lodzi
Kodz, Poland, 92115
Uniwersytecki Szpital Kliniczny
Lodz, Poland, 91-738
Powiatowy Zespot Szpitali w Olesnicy, Oddzial Chorob Wewnetrznych
Olesnica, Poland, 56400
Klinika Endokrynologii i Diabetologii Wieku Rozwojowego
Wroclaw, Poland, 51-376
Romania
S.C. Minimed S.R.L.
Bacau, Romania, 600164
Institutul de Diabet
Bucharest, Romania, 020045
Centrul Medical "Sanatatea ta"
Bucuresti, Romania, 20725
Spitulul Clinic Judetean de Urgenta Cluj
Cluj-Napoca, Romania, 400006
Spitalul Clinic Judetean de Urgenta
Iasi, Romania, 700111
Spitalul Judetean Satu Mare
Satu Mare, Romania, 440055
Spain
Hospital Universitari Dr. Josep Trueta de Girona
Girona, Gerona, Spain, 17007
Hospital Universitario Principe de Asturias
Alcala de Henares, Madrid, Spain, 28805
Hospital Germans Trias i Pujol
Badalona, Spain, 8916
Hospital Clinic I Provincial
Barcelona, Spain, 8036
Fundacion Jimenez Diaz
Madrid, Spain, 28040
Sweden
Universitetssjukhuset i Linkoping
Linkoping, Sweden, 58185
Universitetssjukhuset i Lund
Lund, Sweden, 22185
Sodersjukhuset AB
Stockholm, Sweden, 11883
Ukraine
Donetsk Regional Children Clinical Hospital
Donetsk, Ukraine, 83052
Kharkiv Regional Clinical Children's Hospital
Kharkiv, Ukraine, 61093
V. Danilevsky Institute of Endocrine Pathology Problems
Kharkiv, Ukraine, 61070
Ukranian Children Specialised Clinical Hospital
Kyiv, Ukraine, 02175
Ukrainian Scientific and Practical Center of Endocrine Surgery
Kyiv, Ukraine, 02175
Regional Clinical Endocrinological Dispensary
Vinnitsa, Ukraine, 21010
Zaporizhzhya Regional Pediatric Hospital
Zaporizhzhya, Ukraine, 69035
United Kingdom
Addenbrookes Hospital
Cambridge, Cambridgeshire, United Kingdom, CB20QQ
Royal Devon and Exeter Hospital
Exeter, Devon, United Kingdom, EX25DW
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 July 20, 2014