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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Biological: Teplizumab; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 554
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 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.
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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Double-blind Herold Regimen; Full dose of teplizumab IV for 14 days, repeated at Week 26	Biological: Teplizumab; Daily IV dosing for 14 days, repeated at Week 26; Other Names: MGA031
Experimental: Double-blind 33.3% Herold Regimen; One third full dose of teplizumab IV for 14 days, repeated at Week 26	Biological: Teplizumab; Daily IV dosing for 14 days, repeated at Week 26; Other Names: MGA031
Experimental: Double-blind Curtailed Herold Regimen; Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26	Biological: Teplizumab; Daily IV dosing for 14 days, repeated at Week 26; Other Names: MGA031
Placebo Comparator: Double-blind Placebo; Placebo IV dosing daily for 14 days repeated at Week 26	Drug: Placebo; Daily IV dosing for 14 days, repeated at Week 26
Experimental: Open-label Herold Regimen; Full dose of teplizumab IV for 14 days, repeated at Week 26	Biological: Teplizumab; Daily IV dosing for 14 days, repeated at Week 26; Other Names: MGA031

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in C-peptide Area Under the Curve (AUC) in Segment 2	Comparison among study treatments on the AUC of C-peptide secretory responses following a mixed meal eaten by the subject	104 weeks after randomization
Change From Baseline in C-peptide AUC in Segment 1	AUC of C-peptide secretory responses following a mixed meal eaten by the subject	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%	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%.	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%	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%.	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%.	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%.	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 HbA1c Level of Less Than 7.0%.	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%.	52 weeks after first dose
Mean HbA1c Change From Baseline in Segment 2	Comparison among study treatments of the average change from baseline in HbA1c.	at 104 weeks after randomization
Mean HbA1c Change From Baseline in Segment 1	Comparison among study treatments of the average change from baseline in HbA1c.	104 weeks after first dose

Collaborators and Investigators

• Sponsor: MacroGenics
• Collaborators: Eli Lilly and Company

Publications and helpful links

General Publications

• 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; 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: October 7, 2006
• First Submitted That Met QC Criteria: October 10, 2006
• First Posted (Estimated): October 11, 2006

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Randomized; Double Blind; Controlled Clinical Trial; Parallel Group
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: CP-MGA031-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No