The Protégé Study - Clinical Trial of MGA031 in Children and Adults With Recent-Onset Type 1 Diabetes Mellitus
- Conditions
- Type 1 Diabetes Mellitus
- Interventions
- Drug: PlaceboBiological: Teplizumab
- Registration Number
- NCT00385697
- Lead Sponsor
- MacroGenics
- 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.
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 554
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:
- islet-cell autoantibodies (ICA512/IA-2),
- glutamic acid decarboxylase autoantibodies, or
- 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
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 8 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 8 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Double-blind Placebo Placebo Placebo IV dosing daily for 14 days repeated at Week 26 Double-blind Curtailed Herold Regimen Teplizumab Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26 Double-blind Herold Regimen Teplizumab Full dose of teplizumab IV for 14 days, repeated at Week 26 Double-blind 33.3% Herold Regimen Teplizumab One third full dose of teplizumab IV for 14 days, repeated at Week 26 Open-label Herold Regimen Teplizumab Full dose of teplizumab IV for 14 days, repeated at Week 26
- Primary Outcome Measures
Name Time Method Number of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%. 52 weeks after randomization This is a composite endpoint is based on the proportion of subjects who have both a total daily insulin dose \<0.5 U/Kg/day and an HbAlc level 6.5% at 52 weeks after randomization.
Number of Subjects in Segment 1 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%. 52 weeks after first dose This is a composite endpoint based on the proportion of subjects who have both a total daily insulin dose \<0.5 U/Kg/day and an HbAlc level 6.5%
Mean HbA1c Change From Baseline in Segment 2 52 weeks after randomization Comparison among study treatments of average change from baseline HbA1C. This endpoint will be assessed in a hierarchical manner only if the composite primary endpoint shows a statistically significant difference between arms
Mean HbA1c Change From Baseline in Segment 1 52 weeks after first dose The average change in HbA1c levels after dosing.
- Secondary Outcome Measures
Name Time Method Change From Baseline in C-peptide Area Under the Curve (AUC) in Segment 2 104 weeks after randomization Comparison among study treatments on the AUC of C-peptide secretory responses following a mixed meal eaten by the subject
Change From Baseline in C-peptide AUC in Segment 1 104 weeks after first dose AUC of C-peptide secretory responses following a mixed meal eaten by the subject
Number of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and HbA1c Level of Less Than 6.5% 104 weeks after randomization Comparison among study treatments of a composite endpoint based on the proportion of subjects who have both a total daily insulin dose \<0.5 U/Kg/day and an HbAlc level 6.5%.
Number of Subjects in Segment 1 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and HbA1c Level of Less Than 6.5% 104 weeks after first dose Comparison among study treatments of a composite endpoint based on the proportion of subjects who have both a total daily insulin dose \<0.5 U/Kg/day and an HbAlc level 6.5%.
Number of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and HbA1c Level of Less Than 7.0%. at 52 weeks after randomization Comparison among study treatments of a composite endpoint based on the proportion of subjects who have both a total daily insulin dose \<0.5 U/Kg/day and an HbAlc level 7.0%.
Number of Subjects in Segment 1 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and HbA1c Level of Less Than 7.0%. 52 weeks after first dose Composite endpoint based on the proportion of subjects who have both a total daily insulin dose \<0.5 U/Kg/day and an HbAlc level 7.0%.
Mean HbA1c Change From Baseline in Segment 2 at 104 weeks after randomization Comparison among study treatments of the average change from baseline in HbA1c.
Mean HbA1c Change From Baseline in Segment 1 104 weeks after first dose Comparison among study treatments of the average change from baseline in HbA1c.
Trial Locations
- Locations (115)
Humphrey Diabetes Center
🇺🇸Boise, Idaho, United States
Research Institute of Dallas
🇺🇸Dallas, Texas, United States
Diabetes Medical Center of California
🇺🇸Northridge, California, United States
Richard Hays, MD
🇺🇸Wellington, Florida, United States
NEA Clinic
🇺🇸Jonesboro, Arkansas, United States
Children's Hospital of Western
🇨🇦London, Ontario, Canada
Oxford AIM Clinic
🇨🇦London, Ontario, Canada
Pushpawati Singhania Research Institute
🇮🇳New Delhi, India
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Regional Clinical Endocrinological Dispensary
🇺🇦Vinnitsa, Ukraine
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Saint Barnabas Medical Center
🇺🇸Livingston, New Jersey, United States
Baystate Medical Center
🇺🇸Springfield, Massachusetts, United States
Diabetes and Glandular Disease Research
🇺🇸San Antonio, Texas, United States
Nizam's Institute of Medical Sciences
🇮🇳Hyderabad, Andhra Pradesh, India
Bangalore Diabetes Centre
🇮🇳Bangalore, Karnataka, India
P. Stradins Clinical University Hospital
🇱🇻Riga, Latvia
University Health Sciences Centre
🇨🇦St. John's, Newfoundland and Labrador, Canada
East Tallinn Central Hospital
🇪🇪Tallinn, Estonia
Royal Devon and Exeter Hospital
🇬🇧Exeter, Devon, United Kingdom
Gandhi Endocrinology and Diabetes Centre
🇮🇳Nagpur, Maharashtra, India
The Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Gujarat Endocrine Centre
🇮🇳Ahmedabad, Gujarat, India
Medwin Hospitals
🇮🇳Hyderabad, India
Hospital Mexico-Americano
🇲🇽Guadalajara, Mexico
King George Hospital
🇮🇳Visakhapatnam, Andhra Pradesh, India
Endocrine Clinic
🇮🇳Nashik, Maharashtra, India
Alberta Children's Hospital
🇨🇦Calgary, Alberta, Canada
UAB School of Medicine
🇺🇸Birmingham, Alabama, United States
University of Colorado Health Sciences Center
🇺🇸Aurora, Colorado, United States
Creighton Diabetes Center
🇺🇸Omaha, Nebraska, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
UCSF Medical Center
🇺🇸San Francisco, California, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Christiana Care Research Institute
🇺🇸Newark, Delaware, United States
Atlanta Diabetes Associates
🇺🇸Atlanta, Georgia, United States
Commonwealth Biomedical Research, LLC
🇺🇸Madisonville, Kentucky, United States
University of Iowa Children's Hospital
🇺🇸Iowa City, Iowa, United States
Rocky Mountain Diabetes & Osteoporosis Center
🇺🇸Idaho Falls, Idaho, United States
St. Agnes Hospital
🇺🇸Baltimore, Maryland, United States
Mid-America Diabetes Associates, PA
🇺🇸Wichita, Kansas, United States
Maryland Diabetes & Endocrine Associates
🇺🇸Rockville, Maryland, United States
Alzohaili Medical Consultants
🇺🇸Dearborn, Michigan, United States
University of Medicine & Dentistry of NJ
🇺🇸New Brunswick, New Jersey, United States
Albany Medical Center
🇺🇸Albany, New York, United States
Schneider Children's Hospital
🇺🇸New Hyde Park, New York, United States
Joslin Diabetes Center
🇺🇸Syracuse, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
St. Mary Medical Center
🇺🇸Langhorne, Pennsylvania, United States
Sumter Medical Specialists
🇺🇸Sumter, South Carolina, United States
Methodist Healthcare
🇺🇸Memphis, Tennessee, United States
University Diabetes & Endocrine Consultants
🇺🇸Chattanooga, Tennessee, United States
Spectra Research Center
🇺🇸McAllen, Texas, United States
Pacific Northwest Research Institute
🇺🇸Seattle, Washington, United States
Endocrine Research Specialists
🇺🇸Ogden, Utah, United States
FN Hradec Kralove
🇨🇿Hradec Kralove, Czechia
University of Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Capital District Health Authority
🇨🇦Halifax, Nova Scotia, Canada
FN Brno- Detska nemocnice
🇨🇿Brno, Czechia
Nemocnice Jihlava
🇨🇿Jihlava, Czechia
Fakultni nemocnice v Motole
🇨🇿Praha, Czechia
FN Kralovske Vinohrady
🇨🇿Praha 10, Czechia
Masarykova nemocnice v Usti nad Labem
🇨🇿Usti nad Labem, Czechia
Tartu University Hospital
🇪🇪Puusepa, Tartu, Estonia
Medizinische Universitätsklinik Ulm
🇩🇪Ulm, Baden-Wurttemberg, Germany
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Baden-Wurttemberg, Germany
Charité-Hochschulmedizin Berlin
🇩🇪Berlin, Germany
Universitatsklinik Giessen
🇩🇪Giessen, Germany
Bharti Research Institute of Diabetes & Endocrinology
🇮🇳Karnal, Haryana, India
Diabetes Action Centre
🇮🇳Mumbai, Maharashtra, India
Diabetes Thyroid Hormone Research Institute PVT LTD
🇮🇳Indore, Madhya Pradesh, India
Fortis Escorts Hospital
🇮🇳Jaipur, Rajasthan, India
B.P.Poddar Hospital and Medical Research Ltd
🇮🇳Kolkata, West Bengal, India
Soroka Medical Centre
🇮🇱Beer Sheba, Israel
Hillel Yaffe Medical Center
🇮🇱Hadera, Israel
Rambam Medical Centre
🇮🇱Haifa, Israel
Wolfson Medical Centre
🇮🇱Holon, Israel
National Centre for Childhood and Diabetes
🇮🇱Petach Tikva, Israel
Hospital General de Mexico
🇲🇽Mexico City, Mexico
Chaim Sheba Medical Center
🇮🇱Ramat-Gan, Israel
Hospital CIMA Santa Engracia
🇲🇽San Pedro Garza García, Nuevo Leon, Mexico
Diabeter Center for Pediatric and Adolescent Diabetes Care and Research
🇳🇱Rotterdam, Netherlands
Hospital Central
🇲🇽San Luis Potosí, Mexico
Oddzial Diabetologiczny Klinika Pediatrii
🇵🇱Gdansk, Poland
Samodzielny Publiczny Szpital Kliniczny Akademi Medycznej w Bialymstoku
🇵🇱Bialystok, Poland
Uniwersytecki Szpital Kliniczny
🇵🇱Lodz, Poland
Wojewodzki Specjalistyczny Szpital Dzieciecy
🇵🇱Kielce, Poland
I. Szpital Miejski im. Dr. E. Sonnenberga w Lodzi
🇵🇱Łódź, Poland
Klinika Endokrynologii i Diabetologii Wieku Rozwojowego
🇵🇱Wroclaw, Poland
S.C. Minimed S.R.L.
🇷🇴Bacau, Romania
Institutul de Diabet
🇷🇴Bucharest, Romania
Centrul Medical "Sanatatea ta"
🇷🇴Bucuresti, Romania
Spitulul Clinic Judetean de Urgenta Cluj
🇷🇴Cluj-Napoca, Romania
Spitalul Clinic Judetean de Urgenta
🇷🇴Iasi, Romania
Spitalul Judetean Satu Mare
🇷🇴Satu Mare, Romania
Hospital Universitari Dr. Josep Trueta de Girona
🇪🇸Girona, Gerona, Spain
Hospital Universitario Principe de Asturias
🇪🇸Alcala de Henares, Madrid, Spain
Hospital Germans Trias i Pujol
🇪🇸Badalona, Spain
Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Universitetssjukhuset i Lund
🇸🇪Lund, Sweden
Hospital Clinic I Provincial
🇪🇸Barcelona, Spain
Universitetssjukhuset i Linkoping
🇸🇪Linkoping, Sweden
Sodersjukhuset AB
🇸🇪Stockholm, Sweden
Donetsk Regional Children Clinical Hospital
🇺🇦Donetsk, Ukraine
V. Danilevsky Institute of Endocrine Pathology Problems
🇺🇦Kharkiv, Ukraine
Kharkiv Regional Clinical Children's Hospital
🇺🇦Kharkiv, Ukraine
Ukrainian Scientific and Practical Center of Endocrine Surgery
🇺🇦Kyiv, Ukraine
Ukranian Children Specialised Clinical Hospital
🇺🇦Kyiv, Ukraine
Zaporizhzhya Regional Pediatric Hospital
🇺🇦Zaporizhzhya, Ukraine
Addenbrookes Hospital
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Herz-und Diabetszentrum Nordrhein-Westfalen
🇩🇪Bad Oeynhausen, North Rhine-Westphalia, Germany
Powiatowy Zespot Szpitali w Olesnicy, Oddzial Chorob Wewnetrznych
🇵🇱Olesnica, Poland
DHL Research Centre
🇮🇳Ahmedabad, Gujarat, India
Grant Medical Foundation
🇮🇳Pune, Maharashtra, India