Protege Encore Study- Clinical Trial of Teplizumab (MGA031) in Children and Adults With Recent-Onset Type 1 Diabetes Mellitus

November 30, 2023 updated by: MacroGenics

A Phase 3, Randomized, Double-Blind, Multinational, Placebo-Controlled Study to Evaluate Efficacy and Safety of Teplizumab (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 study is to determine whether teplizumab (MGA031) infusions lead to greater reductions in insulin requirements in conjunction with near normal blood sugar control compared to placebo in patients recently diagnosed with type 1 diabetes.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

254

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Arlon, Belgium, 6700
        • Cliniques du Sud Luxembourg - Vivalia
    • Antwerp
      • Edegem, Antwerp, Belgium, 2650
        • Universitair Ziekenhuis Antwerpen
  • Czechia
      • Brno, Czechia, 62500
        • I. Detska interni klinika,Fakultni nemocnice Brno Detska nemocnice
      • Praha, Czechia, 10034
        • Klinika deti a dorostu FN Kralovske Vinohrady
      • Praha, Czechia, 14021
        • Centrum diabetologie, Institut klinicke a experimentalni mediciny
      • Praha, Czechia, 15006
        • Pediatricka klinika UK 2.LF a FN Motol, Fakultni nemocnice v Motole
      • Usti nad Labem, Czechia, 40113
        • Detska klinika, Masarykova nemocnice v Usti nad Labem, o.z.
  • Finland
      • Kuopio, Finland, 70210
        • Kuopio University Hospital
      • Mikkeli, Finland, 50100
        • Central Hospital of Mikkeli
      • Oulu, Finland, 90029
        • Oulu University Hospital
  • France
      • Besançon, France, 25030
        • CHU de Besancon
      • Brest, France, 29609
        • CHU de Brest Hôpital de la Cavale Blanche
      • Corbeil-Essonnes, France, 91106
        • Centre Hospitalier Sud Francilien
      • Pessac, France, 33604
        • CHU de Bordeaux
      • Reims, France, 51092
        • CHU de Reims
      • Strasbourg, France, 67091
        • Hôpitaux Universitaires de Strasbourg Hôpital Civil
  • Germany
      • Bad Nauheim, Germany, 61231
        • Diabetes-Klinik Bad Nauheim GmbH
      • Bad Oeynhausen, Germany, 32545
        • Herz und Diabeteszentrum Nordrhein-Westfallen
      • Berlin, Germany, 12200
        • Charite, Campus Benjamin Franklin
      • Düsseldorf, Germany, 20225
        • Universitatsklinikum Dusseldorf
      • Giessen, Germany, 35392
        • Universitatsklinik Giessen
      • Hamburg, Germany, 22559
        • Asklepios Westklinikum Hamburg
      • Hannover, Germany, 30173
        • Kinderkrankenhaus auf der Bult
      • Heidelberg, Germany, 69120
        • Universitätsklinikum Heidelberg
  • India
    • Andhra Pradesh
      • Hyderabad, Andhra Pradesh, India, 500001
        • Medwin Hospitals
      • Visakhapatnam, Andhra Pradesh, India, 530002
        • King George Hospital
    • Delhi
      • New Delhi, Delhi, India, 110002
        • Maulana Azad Medical College and Associated Hospitals
    • Gujarat
      • Ahmedabad, Gujarat, India, 380015
        • DHL Research Centre
    • Karnataka
      • Bangalore, Karnataka, India, 560043
        • Bangalore Diabetes Centre
    • Kerala
      • Trivandrum, Kerala, India, 695011
        • Health & Research Centre
    • Maharashtra
      • Nagpur, Maharashtra, India, 440010
        • Gandhi's Research Institute
      • Pune, Maharashtra, India, 411001
        • Grant Medical Foundation
      • Pune, Maharashtra, India, 411011
        • KEM Hospital Research Center
    • Orissa
      • Bhubaneswar, Orissa, India, 751023
        • Kalinga Hospital Limited
    • Pradesh
      • Madhya, Pradesh, India, 452001
        • Diabetes-Thyroid-Hormone Research Institute Pvt. Ltd.
    • Punjab
      • Ludhiana, Punjab, India, 141001
        • Dayanand Medical College and Hospital
    • Rajasthan
      • Jaipur, Rajasthan, India, 302017
        • Fortis Escorts Hospital
    • Uttar Pradesh
      • Ghaziabad, Uttar Pradesh, India, 201002
        • Hormone Care & Research Center
    • West Bengal
      • Kolkata, West Bengal, India, 700053
        • B. P. Poddar Hospital & Medical Research Limited
      • Kolkata, West Bengal, India, 700054
        • Apollo Glenagles Hospital
  • Israel
      • Hadera, Israel, 38100
        • Hillel Yaffe Medical Center
      • Haifa, Israel, 31096
        • Mayer Children's Hospital of Haifa
      • Holon, Israel, 58100
        • The E. Wolfson Medical Center
      • Petach-Tikva, Israel, 49202
        • Schneider Children's Medical
      • Ramat-Gan, Israel, 52621
        • The Safra Children's Hospital, The Chaim Sheba Medical Center
  • Italy
      • Modena, Italy, 41124
        • Struttura Complessa di Pediatria, Azienda Ospedaliero-Universitaria di Modena,
      • Pisa, Italy, 56124
        • U.O. di Malattie Metaboliche e Diabetologia
      • Pisa, Italy, 16132
        • U.O. di Malattie del Metabolismo
  • Mexico
      • Mexico, Distrito Federal, Mexico, 11650
        • Centro Especializado en Diabetes, Obesidad y Prevención de Enfermedades Cardiovasculares, S.C.
    • Nuevo León
      • Monterrey, Nuevo León, Mexico, 64000
        • Hospital y Clinica OCA / Monterrey International Research Center
    • Yucatan
      • Merida, Yucatan, Mexico, 97070
        • Medical Care & Research
  • Netherlands
      • Rotterdam, Netherlands, 3011 TG
        • Stichting Diabeter
  • Poland
      • Bialystok, Poland, 15-276
        • Uniwersytecki Szpital Kliniczny w Bialymstoku
      • Gdansk, Poland, 80-952
        • Uniwersyteckie Centrum Kliniczne
      • Kielce, Poland, 25-734
        • Wojewodzki Specjalistyczny Szpital Dzieciecy
      • Warszawa, Poland, 01-184
        • Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie-Filia
      • Wroclaw, Poland, 50-376
        • Samodzielny Publiczny Szpital Kliniczny Nr1 we Wroclawiu
      • Łódź, Poland, 91-738
        • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Uniwersytecki Szpital Kliniczny Nr 4
  • Romania
      • Bacau, Romania, 600164
        • S.C. Minimed S.R.L.
      • Bucuresti, Romania, 020045
        • Institutul National De Diabet, Nutritie si Boli Metabolice
      • Satu-Mare, Romania, 440055
        • Spitalul Judetean de Urgenta Satu Mare
  • Spain
      • Alcala de Henares, Spain, 28805
        • Hospital Universitario Príncipe de Asturias
      • Girona, Spain, 17007
        • Hospital Dr. Josep Trueta
  • Ukraine
      • Donetsk, Ukraine, 83052
        • Donetsk Regional Children Clinical Hospital
      • Ivano-Frankivsk, Ukraine, 76008
        • Ivano-Frankivsk Regional Clinical Hospital
      • Ivano-Frankivsk, Ukraine, 76014
        • Ivano-Frankivsk State Regional Pediatric Clinical Hospital
      • Kharkiv, Ukraine, 61093
        • Kharkiv Regional Clinical Children Hospital, Department of Endocrinology
      • Kyiv, Ukraine, 01135
        • Ukrainian Children Specialized Clinical Hospital
      • Kyiv, Ukraine, 04114
        • Institute of Endocrinology and Metabolism named after V.Komisarenko of AMS Ukraine
      • Vinnitsa, Ukraine, 21010
        • Regional Clinical Endocrinology Dispensary of MoH Ukraine
  • United Kingdom
      • Bristol, United Kingdom, BS1 3NY
        • University of Bristol Henery Wellcome laboratories for Integrative Neuroscience and Endocrinology,
      • Liverpool, United Kingdom, L9 7AL
        • Aintree University Hospitals NHS Foundation Trust
      • London, United Kingdom, SE1 9RT
        • Kings College, Clinical Research Unit, Department of Diabetes and Endocrinology
      • Nottingham, United Kingdom, NG7 2UH
        • Queens Medical Centre, Diabetes and Endocrinology Unit
      • Sheffield, United Kingdom, S10 2IH
        • Sheffield Children's Hospital NHS Foundation Trust
    • Warwickshire
      • Nuneaton, Warwickshire, United Kingdom, CV10 7DJ
        • George Eliot Hospital NHS Trust
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham
    • Arkansas
      • Jonesboro, Arkansas, United States, 72401
        • NEA Clinic
      • Little Rock, Arkansas, United States, 72272
        • Arkansas Children's Hospital
    • California
      • Costa Mesa, California, United States, 92626
        • Clinical Innovations Inc. Research Facility
      • Los Angeles, California, United States, 90036
        • Axis Clinical Trials
      • Orange, California, United States, 92868
        • Diabetes Associates Medical Group, Inc
      • Riverside, California, United States, 92506
        • Clinical Innovations, Inc.
      • San Diego, California, United States, 92120
        • San Diego Clinical Trials
      • Ventura, California, United States, 93003
        • Ronald Chochinov Md Inc
    • 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
    • Illinois
      • Chicago, Illinois, United States, 60612
        • John H Stoger Jr. Hospital of Cook County, Cook County Hospital
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University School of Medicine
    • Iowa
      • Iowa City, Iowa, United States, 52242-1083
        • University of Iowa Children's Hospital
    • Kansas
      • Wichita, Kansas, United States, 67211
        • Mid-America Diabetes Associates
    • 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
    • Michigan
      • Dearborn, Michigan, United States, 48126
        • Alzohaili Medical Consultants
    • Minnesota
      • Saint Paul, Minnesota, United States, 55102
        • Children's Hospitals and Clinics of Minnesota
    • Missouri
      • Columbia, Missouri, United States, 65212
        • University of Missouri - Columbia, Cosmopolitan Diabetes and Endocrinology
      • Kansas City, Missouri, United States, 64108
        • The Children's Mercy Hospital
    • New Jersey
      • Livingston, New Jersey, United States, 07039
        • Saint Barnabas Medical Center
    • New York
      • Albany, New York, United States, 12208
        • Albany Medical College
      • Cooperstown, New York, United States, 13326
        • Bassett Healthcare
    • North Carolina
      • Greenville, North Carolina, United States, 27834
        • East Carolina University, Brody School of Medicine
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
    • South Carolina
      • Greenville, South Carolina, United States, 29615
        • GHS Pediatric Endocrinology
    • Tennessee
      • Bartlett, Tennessee, United States, 38133
        • AM Diabetes & Endocrinology Center
      • Chattanooga, Tennessee, United States, 37403
        • University Diabetes & Endocrine Consultants
      • Memphis, Tennessee, United States, 38103
        • LeBonheur Children's Medical Center
    • Texas
      • Dallas, Texas, United States, 75231
        • Research Institute Of Dallas
      • Houston, Texas, United States, 77074
        • Southwest Clinical Trials
      • Houston, Texas, United States, 77081
        • Houston Center for Clinical Research
      • Irving, Texas, United States, 75061
        • Medical & Surgical Clinic of Irving
      • San Antonio, Texas, United States, 78217
        • InVisions Consultants, LLC
      • San Antonio, Texas, United States, 78229
        • Diabetes and Glandular Disease Research Associates, PA
    • Utah
      • Ogden, Utah, United States, 84403
        • Endocrine Research Specialists
    • Virginia
      • Richmond, Virginia, United States, 23219
        • Virginia Commonwealth University-Division of Pediatric Endocrinology & Metabolism
    • Washington
      • Seattle, Washington, United States, 98122
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

8 years to 35 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Subjects 8-35 years old
  2. Body weight > 36 Kg
  3. Diagnosis of diabetes mellitus according to the American Diabetes Association (ADA) criteria
  4. Randomization on Study Day 0 within 12 weeks of first visit to any physician for symptoms or signs of diabetes
  5. Requires insulin for T1DM or has required insulin at some time between diagnosis and administration of study drug
  6. Detectable fasting or stimulated C-peptide level (above the lower limit of the reportable range of the assay) at screening

  7. Diagnosis of T1DM as evidenced by one positive result on testing for any of the following antibodies at screening:

    • Islet-cell autoantibodies 512 (ICA512)/islet antigen-2 (IA-2),
    • Glutamic acid decarboxylase (GAD) autoantibodies, or
    • Insulin autoantibodies (in subjects on insulin for more than 2 weeks, ICA512/IA-2 or GAD must be positive).

Exclusion Criteria:

  1. Prior administration of a monoclonal antibody-within the 1 year before randomization
  2. Participation in any type of therapeutic drug or vaccine clinical trial within the last 12 weeks before randomization at Study Day 0
  3. Any medical condition that, in the opinion of the investigator, would interfere with safe completion of the trial
  4. Pregnant females or lactating females who intend to provide their own breast milk to the baby during the study
  5. Current therapy with GLP-1 receptor agonists (e.g., exenatide or pramlintide), or any other agents that might stimulate pancreatic beta cell regeneration or insulin secretion
  6. Current treatment with oral antidiabetic agents
  7. Evidence of active or latent tuberculosis

  8. Vaccination with a live virus or organism within the 8 weeks before randomization continuing through Week 52 of the study.

    • Influenza vaccination with a killed virus, including booster vaccinations, within 4 weeks before or after each dosing cycle.
    • Vaccination with other antigens or killed organisms within 8 weeks before or after each dosing cycle
  9. Any infectious mononucleosis-like illness within the 6 months before randomization

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Herold Regimen
14-day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-14. Repeat at Week 26
Biological: Teplizumab Herold Regimen
Full dose of teplizumab IV for 14 days, repeated at Week 26
Other Names:
  • MGA031
Experimental: 33.3% Herold Regimen
Subjects received a 14-day cycle of teplizumab consisting of daily IV doses of 17 µg/m2, 34 µg/m2, 68 µg/m2, and 136 µg/m2 on Study Days 1-4, respectively, and one dose of 273 µg/m2 on each of Study Days 5-14. Repeat at Week 26
Biological: Teplizumab 33.3% Herold Regimen
One third full dose of teplizumab IV for 14 days, repeated at Week 26
Other Names:
  • MGA031
Experimental: Curtailed Herold Regimen
Subjects received a 6 day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-6, followed by 8 days of IV placebo (Study Days 7-14). Repeat at Week 26
Biological: Teplizumab Curtailed Herold Regimen
Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26
Placebo Comparator: Placebo
14-day cycle of placebo consisting of daily IV doses. Repeat at Week 26
Drug: Placebo
IV dosing daily for 14 days repeated at Week 26

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proportion of Subjects 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%.
Time Frame: 52 weeks after randomization
52 weeks after randomization
Mean Change From Baseline in HbA1c Between Teplizumab and Placebo
Time Frame: 52 weeks after randomization
52 weeks after randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Change in Beta-cell Function as Measured by C-peptide Secretory Response Following a Mixed Meal
Time Frame: 52 weeks after randomization
52 weeks after randomization
The Change in Beta-cell Function as Measured by C-peptide Secretory Response Following a Mixed Meal
Time Frame: 104 weeks after randomization
104 weeks after randomization
Mean Number of Total, Major, Minor and Nocturnal Hypoglycemia Events
Time Frame: Throughout the study up to 2 years
Number of hypoglycemic events by type per participant
Throughout the study up to 2 years
Mean Number of Daily Insulin Injections
Time Frame: 52 weeks after randomization
52 weeks after randomization
Number of Subjects 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%.
Time Frame: 104 weeks after randomization
104 weeks after randomization
The Proportion of Subjects Who Have Both a Total Daily Insulin Dose < 0.5 U/Kg/Day and Hemoglobin A1c (HbA1c) Level < 7.0%
Time Frame: 52 weeks after randomization
52 weeks after randomization
The Mean HbA1c Change From Baseline
Time Frame: 104 weeks after randomization
104 weeks after randomization
Number of Participants With Adverse Events
Time Frame: throughout the study, up to 104 weeks
throughout the study, up to 104 weeks
Number of Participants With Serious Adverse Events
Time Frame: throughout the study, up to 104 weeks
throughout the study, up to 104 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MacroGenics

Collaborators

Eli Lilly and Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (Actual)

April 1, 2012

Study Completion (Actual)

July 1, 2012

Study Registration Dates

First Submitted

June 12, 2009

First Submitted That Met QC Criteria

June 12, 2009

First Posted (Estimated)

June 15, 2009

Study Record Updates

Last Update Posted (Estimated)

December 20, 2023

Last Update Submitted That Met QC Criteria

November 30, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CP-MGA031-03

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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