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
1 other identifier
interventional
554
15 countries
110
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Oct 2006
Longer than P75 for phase_2
110 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2006
CompletedFirst Submitted
Initial submission to the registry
October 7, 2006
CompletedFirst Posted
Study publicly available on registry
October 11, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2011
CompletedResults Posted
Study results publicly available
December 5, 2023
CompletedDecember 5, 2023
November 1, 2023
3.7 years
October 7, 2006
February 23, 2023
November 30, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
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%.
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.
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%.
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%
52 weeks after first dose
Mean HbA1c Change From Baseline in Segment 2
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
52 weeks after randomization
Mean HbA1c Change From Baseline in Segment 1
The average change in HbA1c levels after dosing.
52 weeks after first dose
Secondary Outcomes (8)
Change From Baseline in C-peptide Area Under the Curve (AUC) in Segment 2
104 weeks after randomization
Change From Baseline in C-peptide AUC in Segment 1
104 weeks after first dose
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
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
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
- +3 more secondary outcomes
Study Arms (5)
Double-blind Herold Regimen
EXPERIMENTALFull dose of teplizumab IV for 14 days, repeated at Week 26
Double-blind 33.3% Herold Regimen
EXPERIMENTALOne third full dose of teplizumab IV for 14 days, repeated at Week 26
Double-blind Curtailed Herold Regimen
EXPERIMENTALFull dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26
Double-blind Placebo
PLACEBO COMPARATORPlacebo IV dosing daily for 14 days repeated at Week 26
Open-label Herold Regimen
EXPERIMENTALFull dose of teplizumab IV for 14 days, repeated at Week 26
Interventions
Daily IV dosing for 14 days, repeated at Week 26
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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)
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- MacroGenicslead
- Eli Lilly and Companycollaborator
Study Sites (115)
UAB School of Medicine
Birmingham, Alabama, 35294, United States
NEA Clinic
Jonesboro, Arkansas, 72401, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202, United States
Diabetes Medical Center of California
Northridge, California, 91325, United States
UCSF Medical Center
San Francisco, California, 94143, United States
University of Colorado Health Sciences Center
Aurora, Colorado, 80045, United States
Yale University
New Haven, Connecticut, 06519, United States
Christiana Care Research Institute
Newark, Delaware, 19713, United States
Richard Hays, MD
Wellington, Florida, 33414, United States
Atlanta Diabetes Associates
Atlanta, Georgia, 30309, United States
Humphrey Diabetes Center
Boise, Idaho, 87702, United States
Rocky Mountain Diabetes & Osteoporosis Center
Idaho Falls, Idaho, 83404, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
University of Iowa Children's Hospital
Iowa City, Iowa, 52242-1083, United States
Mid-America Diabetes Associates, PA
Wichita, Kansas, 67211, United States
Commonwealth Biomedical Research, LLC
Madisonville, Kentucky, 42431, United States
St. Agnes Hospital
Baltimore, Maryland, 21229, United States
Maryland Diabetes & Endocrine Associates
Rockville, Maryland, 20852, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Baystate Medical Center
Springfield, Massachusetts, 01199, United States
Alzohaili Medical Consultants
Dearborn, Michigan, 48126, United States
The Children's Mercy Hospital
Kansas City, Missouri, 64108, United States
Creighton Diabetes Center
Omaha, Nebraska, 68131, United States
Saint Barnabas Medical Center
Livingston, New Jersey, 07039, United States
University of Medicine & Dentistry of NJ
New Brunswick, New Jersey, 08901, United States
Albany Medical Center
Albany, New York, 12208, United States
Schneider Children's Hospital
New Hyde Park, New York, 11040, United States
Joslin Diabetes Center
Syracuse, New York, 13214, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
St. Mary Medical Center
Langhorne, Pennsylvania, 19047, United States
Sumter Medical Specialists
Sumter, South Carolina, 29150, United States
University Diabetes & Endocrine Consultants
Chattanooga, Tennessee, 37403, United States
Methodist Healthcare
Memphis, Tennessee, 38104, United States
Research Institute of Dallas
Dallas, Texas, 75231, United States
Spectra Research Center
McAllen, Texas, 78503, United States
Diabetes and Glandular Disease Research
San Antonio, Texas, 78229, United States
Endocrine Research Specialists
Ogden, Utah, 84403, United States
Pacific Northwest Research Institute
Seattle, Washington, 98122, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8, Canada
University of Manitoba
Winnipeg, Manitoba, R3E0Z2, Canada
University Health Sciences Centre
St. John's, Newfoundland and Labrador, A1B3V6, Canada
Capital District Health Authority
Halifax, Nova Scotia, B3H2YN, Canada
Oxford AIM Clinic
London, Ontario, N6A 5R9, Canada
Children's Hospital of Western
London, Ontario, N6A5W9, Canada
FN Brno- Detska nemocnice
Brno, 62500, Czechia
FN Hradec Kralove
Hradec Králové, 50005, Czechia
Nemocnice Jihlava
Jihlava, 58633, Czechia
FN Kralovske Vinohrady
Prague, 10034, Czechia
Fakultni nemocnice v Motole
Prague, 150 06, Czechia
Masarykova nemocnice v Usti nad Labem
Ústí nad Labem, 40113, Czechia
Tartu University Hospital
Puusepa, Tartu, 51014, Estonia
East Tallinn Central Hospital
Tallinn, Estonia
Universitätsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69120, Germany
Medizinische Universitätsklinik Ulm
Ulm, Baden-Wurttemberg, 89070, Germany
Herz-und Diabetszentrum Nordrhein-Westfalen
Bad Oeynhausen, North Rhine-Westphalia, 32545, Germany
Charité-Hochschulmedizin Berlin
Berlin, 12200, Germany
Universitatsklinik Giessen
Giessen, 35392, Germany
Nizam's Institute of Medical Sciences
Hyderabad, Andhra Pradesh, 500082, India
King George Hospital
Visakhapatnam, Andhra Pradesh, 530002, India
Gujarat Endocrine Centre
Ahmedabad, Gujarat, 380006, India
DHL Research Centre
Ahmedabad, Gujarat, 380015, India
Bharti Research Institute of Diabetes & Endocrinology
Karnāl, Haryana, 132001, India
Bangalore Diabetes Centre
Bangalore, Karnataka, 560043, India
Diabetes Thyroid Hormone Research Institute PVT LTD
Indore, Madhya Pradesh, 452001, India
Diabetes Action Centre
Mumbai, Maharashtra, 400067, India
Gandhi Endocrinology and Diabetes Centre
Nagpur, Maharashtra, 440010, India
Endocrine Clinic
Nashik, Maharashtra, 422013, India
Grant Medical Foundation
Pune, Maharashtra, 411001, India
Fortis Escorts Hospital
Jaipur, Rajasthan, 302017, India
B.P.Poddar Hospital and Medical Research Ltd
Kolkata, West Bengal, 700053, India
Medwin Hospitals
Hyderabad, 500001, India
Pushpawati Singhania Research Institute
New Delhi, 110017, India
Soroka Medical Centre
Beersheba, 84101, Israel
Hillel Yaffe Medical Center
Hadera, 38100, Israel
Rambam Medical Centre
Haifa, 31096, Israel
Wolfson Medical Centre
Holon, 58100, Israel
National Centre for Childhood and Diabetes
Petah Tikva, 49202, Israel
Chaim Sheba Medical Center
Ramat Gan, 56261, Israel
P. Stradins Clinical University Hospital
Riga, 1002, Latvia
Hospital CIMA Santa Engracia
San Pedro Garza García, Nuevo León, 66260, Mexico
Hospital Mexico-Americano
Guadalajara, 44620, Mexico
Hospital General de Mexico
Mexico City, 06726, Mexico
Hospital Central
San Luis Potosí City, 78240, Mexico
Diabeter Center for Pediatric and Adolescent Diabetes Care and Research
Rotterdam, 3011TG, Netherlands
Samodzielny Publiczny Szpital Kliniczny Akademi Medycznej w Bialymstoku
Bialystok, 15-276, Poland
Oddzial Diabetologiczny Klinika Pediatrii
Gdansk, 80-952, Poland
Wojewodzki Specjalistyczny Szpital Dzieciecy
Kielce, 25-734, Poland
Uniwersytecki Szpital Kliniczny
Lodz, 91-738, Poland
I. Szpital Miejski im. Dr. E. Sonnenberga w Lodzi
Lodz, 92115, Poland
Powiatowy Zespot Szpitali w Olesnicy, Oddzial Chorob Wewnetrznych
Oleśnica, 56400, Poland
Klinika Endokrynologii i Diabetologii Wieku Rozwojowego
Wroclaw, 51-376, Poland
S.C. Minimed S.R.L.
Bacau, 600164, Romania
Institutul de Diabet
Bucharest, 020045, Romania
Centrul Medical "Sanatatea ta"
Bucharest, 20725, Romania
Spitulul Clinic Judetean de Urgenta Cluj
Cluj-Napoca, 400006, Romania
Spitalul Clinic Judetean de Urgenta
Iași, 700111, Romania
Spitalul Judetean Satu Mare
Satu Mare, 440055, Romania
Hospital Universitari Dr. Josep Trueta de Girona
Girona, Gerona, 17007, Spain
Hospital Universitario Principe de Asturias
Alcalá de Henares, Madrid, 28805, Spain
Hospital Germans Trias i Pujol
Badalona, 8916, Spain
Hospital Clinic I Provincial
Barcelona, 8036, Spain
Fundacion Jimenez Diaz
Madrid, 28040, Spain
Universitetssjukhuset i Linkoping
Linköping, 58185, Sweden
Universitetssjukhuset i Lund
Lund, 22185, Sweden
Sodersjukhuset AB
Stockholm, 11883, Sweden
Donetsk Regional Children Clinical Hospital
Donetsk, 83052, Ukraine
V. Danilevsky Institute of Endocrine Pathology Problems
Kharkiv, 61070, Ukraine
Kharkiv Regional Clinical Children's Hospital
Kharkiv, 61093, Ukraine
Ukrainian Scientific and Practical Center of Endocrine Surgery
Kyiv, 02175, Ukraine
Ukranian Children Specialised Clinical Hospital
Kyiv, 02175, Ukraine
Regional Clinical Endocrinological Dispensary
Vinnitsa, 21010, Ukraine
Zaporizhzhya Regional Pediatric Hospital
Zaporizhzhya, 69035, Ukraine
Addenbrookes Hospital
Cambridge, Cambridgeshire, CB20QQ, United Kingdom
Royal Devon and Exeter Hospital
Exeter, Devon, EX25DW, United Kingdom
Related Publications (2)
Ajmal N, Bogart MC, Khan P, Max-Harry IM, Healy AM, Nunemaker CS. Identifying Promising Immunomodulators for Type 1 Diabetes (T1D) and Islet Transplantation. J Diabetes Res. 2024 Dec 20;2024:5151171. doi: 10.1155/jdr/5151171. eCollection 2024.
PMID: 39735417DERIVEDSherry 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; Protege Trial Investigators. Teplizumab for treatment of type 1 diabetes (Protege study): 1-year results from a randomised, placebo-controlled trial. Lancet. 2011 Aug 6;378(9790):487-97. doi: 10.1016/S0140-6736(11)60931-8. Epub 2011 Jun 28.
PMID: 21719095DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Sharon Rowland
- Organization
- Provention Bio, Inc
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 7, 2006
First Posted
October 11, 2006
Study Start
October 1, 2006
Primary Completion
June 1, 2010
Study Completion
August 1, 2011
Last Updated
December 5, 2023
Results First Posted
December 5, 2023
Record last verified: 2023-11
Data Sharing
- IPD Sharing
- Will not share