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

Phase 3

Terminated

Conditions: Type 1 Diabetes Mellitus

Interventions: Drug: Placebo
Biological: Teplizumab 33.3% Herold Regimen
Biological: Teplizumab Herold Regimen
Biological: Teplizumab Curtailed Herold Regimen

Registration Number: NCT00920582

Lead Sponsor: MacroGenics

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 254

Inclusion Criteria

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

Prior administration of a monoclonal antibody-within the 1 year before randomization
Participation in any type of therapeutic drug or vaccine clinical trial within the last 12 weeks before randomization at Study Day 0
Any medical condition that, in the opinion of the investigator, would interfere with safe completion of the trial
Pregnant females or lactating females who intend to provide their own breast milk to the baby during the study
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
Current treatment with oral antidiabetic agents
Evidence of active or latent tuberculosis
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
Any infectious mononucleosis-like illness within the 6 months before randomization

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	14-day cycle of placebo consisting of daily IV doses. Repeat at Week 26
33.3% Herold Regimen	Teplizumab 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
Herold Regimen	Teplizumab 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
Curtailed Herold Regimen	Teplizumab 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

Primary Outcome Measures

Name	Time	Method
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%.	52 weeks after randomization
Mean Change From Baseline in HbA1c Between Teplizumab and Placebo	52 weeks after randomization

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Serious Adverse Events	throughout the study, up to 104 weeks
The Mean HbA1c Change From Baseline	104 weeks after randomization
The Change in Beta-cell Function as Measured by C-peptide Secretory Response Following a Mixed Meal	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%	52 weeks after randomization
Number of Participants With Adverse Events	throughout the study, up to 104 weeks
Mean Number of Total, Major, Minor and Nocturnal Hypoglycemia Events	Throughout the study up to 2 years	Number of hypoglycemic events by type per participant
Mean Number of Daily Insulin Injections	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%.	104 weeks after randomization

Trial Locations

Locations (118): University of Missouri - Columbia, Cosmopolitan Diabetes and Endocrinology
🇺🇸
Columbia, Missouri, United States
University Diabetes & Endocrine Consultants
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Chattanooga, Tennessee, United States
Research Institute of Dallas
🇺🇸
Dallas, Texas, United States
KEM Hospital Research Center
🇮🇳
Pune, Maharashtra, India
Cliniques du Sud Luxembourg - Vivalia
🇧🇪
Arlon, Belgium
Stichting Diabeter
🇳🇱
Rotterdam, Netherlands
Uniwersytecki Szpital Kliniczny w Bialymstoku
🇵🇱
Bialystok, Poland
Wojewódzki Specjalistyczny Szpital Dzieciecy
🇵🇱
Kielce, Poland
Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie-Filia
🇵🇱
Warszawa, Poland
Donetsk Regional Children Clinical Hospital
🇺🇦
Donetsk, Ukraine
Ivano-Frankivsk Regional Clinical Hospital
🇺🇦
Ivano-Frankivsk, Ukraine
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Houston Center for Clinical Research
🇺🇸
Houston, Texas, United States
University of Washington
🇺🇸
Seattle, Washington, United States
Indiana University School of Medicine
🇺🇸
Indianapolis, Indiana, United States
San Diego Clinical Trials
🇺🇸
San Diego, California, United States
InVisions Consultants, LLC
🇺🇸
San Antonio, Texas, United States
Diabetes and Glandular Disease Research Associates, PA
🇺🇸
San Antonio, Texas, United States
Struttura Complessa di Pediatria, Azienda Ospedaliero-Universitaria di Modena,
🇮🇹
Modena, Italy
U.O. di Malattie del Metabolismo
🇮🇹
Pisa, Italy
U.O. di Malattie Metaboliche e Diabetologia
🇮🇹
Pisa, Italy
Axis Clinical Trials
🇺🇸
Los Angeles, California, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Christiana Care Research Institute
🇺🇸
Newark, Delaware, United States
Ronald Chochinov Md Inc
🇺🇸
Ventura, California, United States
NEA Clinic
🇺🇸
Jonesboro, Arkansas, United States
Clinical Innovations Inc. Research Facility
🇺🇸
Costa Mesa, California, United States
Atlanta Diabetes Associates
🇺🇸
Atlanta, Georgia, United States
Richard Hays, MD
🇺🇸
Wellington, Florida, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
Diabetes Associates Medical Group, Inc
🇺🇸
Orange, California, United States
Clinical Innovations, Inc.
🇺🇸
Riverside, California, United States
John H Stoger Jr. Hospital of Cook County, Cook County Hospital
🇺🇸
Chicago, Illinois, United States
University of Iowa Children's Hospital
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Iowa City, Iowa, United States
Maryland Diabetes & Endocrine Associates
🇺🇸
Rockville, Maryland, United States
Asklepios Westklinikum Hamburg
🇩🇪
Hamburg, Germany
Mid-America Diabetes Associates
🇺🇸
Wichita, Kansas, United States
St. Agnes Hospital
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Baltimore, Maryland, United States
Alzohaili Medical Consultants
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Dearborn, Michigan, United States
CHU de Besançon
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Besançon, France
Children's Hospitals and Clinics of Minnesota
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Saint Paul, Minnesota, United States
Detska klinika, Masarykova nemocnice v Usti nad Labem, o.z.
🇨🇿
Usti nad Labem, Czechia
Albany Medical College
🇺🇸
Albany, New York, United States
CHU de Reims
🇫🇷
Reims, France
Children's Hospital of Philadelphia
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Philadelphia, Pennsylvania, United States
Universitatsklinik Giessen
🇩🇪
Giessen, Germany
Diabetes-Klinik Bad Nauheim GmbH
🇩🇪
Bad Nauheim, Germany
AM Diabetes & Endocrinology Center
🇺🇸
Bartlett, Tennessee, United States
GHS Pediatric Endocrinology
🇺🇸
Greenville, South Carolina, United States
Endocrine Research Specialists
🇺🇸
Ogden, Utah, United States
Southwest Clinical Trials
🇺🇸
Houston, Texas, United States
Oulu University Hospital
🇫🇮
Oulu, Finland
Centrum diabetologie, Institut klinicke a experimentalni mediciny
🇨🇿
Praha, Czechia
Medical & Surgical Clinic of Irving
🇺🇸
Irving, Texas, United States
CHU de Bordeaux
🇫🇷
Pessac, France
Kuopio University Hospital
🇫🇮
Kuopio, Finland
Central Hospital of Mikkeli
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Mikkeli, Finland
Pediatricka klinika UK 2.LF a FN Motol, Fakultni nemocnice v Motole
🇨🇿
Praha, Czechia
Medwin Hospitals
🇮🇳
Hyderabad, Andhra Pradesh, India
Herz und Diabeteszentrum Nordrhein-Westfallen
🇩🇪
Bad Oeynhausen, Germany
Charite, Campus Benjamin Franklin
🇩🇪
Berlin, Germany
Bangalore Diabetes Centre
🇮🇳
Bangalore, Karnataka, India
Kinderkrankenhaus auf der Bult
🇩🇪
Hannover, Germany
King George Hospital
🇮🇳
Visakhapatnam, Andhra Pradesh, India
Maulana Azad Medical College and Associated Hospitals
🇮🇳
New Delhi, Delhi, India
Hormone Care & Research Center
🇮🇳
Ghaziabad, Uttar Pradesh, India
Diabetes-Thyroid-Hormone Research Institute Pvt. Ltd.
🇮🇳
Madhya, Pradesh, India
Fortis Escorts Hospital
🇮🇳
Jaipur, Rajasthan, India
Dayanand Medical College and Hospital
🇮🇳
Ludhiana, Punjab, India
Hospital Dr. Josep Trueta
🇪🇸
Girona, Spain
Sheffield Children's Hospital NHS Foundation Trust
🇬🇧
Sheffield, United Kingdom
Hospital Universitario Principe de Asturias
🇪🇸
Alcala de Henares, Spain
Uniwersyteckie Centrum Kliniczne
🇵🇱
Gdansk, Poland
Queens Medical Centre, Diabetes and Endocrinology Unit
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Nottingham, United Kingdom
Regional Clinical Endocrinology Dispensary of MoH Ukraine
🇺🇦
Vinnitsa, Ukraine
Kings College, Clinical Research Unit, Department of Diabetes and Endocrinology
🇬🇧
London, United Kingdom
University of Bristol Henery Wellcome laboratories for Integrative Neuroscience and Endocrinology,
🇬🇧
Bristol, United Kingdom
CHU de Brest Hôpital de la Cavale Blanche
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Brest, France
Centre Hospitalier Sud Francilien
🇫🇷
Corbeil-Essonnes, France
Hôpitaux Universitaires de Strasbourg Hôpital Civil
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Strasbourg, France
Universitatsklinikum Heidelberg
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Heidelberg, Germany
The Children's Mercy Hospital
🇺🇸
Kansas City, Missouri, United States
Virginia Commonwealth University-Division of Pediatric Endocrinology & Metabolism
🇺🇸
Richmond, Virginia, United States
I. Detska interni klinika,Fakultni nemocnice Brno Detska nemocnice
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Brno, Czechia
East Carolina University, Brody School of Medicine
🇺🇸
Greenville, North Carolina, United States
Bassett Healthcare
🇺🇸
Cooperstown, New York, United States
Klinika deti a dorostu FN Kralovske Vinohrady
🇨🇿
Praha, Czechia
Universitätsklinikum Düsseldorf
🇩🇪
Düsseldorf, Germany
Kalinga Hospital Limited
🇮🇳
Bhubaneswar, Orissa, India
Hillel Yaffe Medical Center
🇮🇱
Hadera, Israel
Aintree University Hospitals NHS Foundation Trust
🇬🇧
Liverpool, United Kingdom
Ivano-Frankivsk State Regional Pediatric Clinical Hospital
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Ivano-Frankivsk, Ukraine
Saint Barnabas Medical Center
🇺🇸
Livingston, New Jersey, United States
Universitair Ziekenhuis Antwerpen
🇧🇪
Edegem, Antwerp, Belgium
Arkansas Children's Hospital
🇺🇸
Little Rock, Arkansas, United States
LeBonheur Children's Medical Center
🇺🇸
Memphis, Tennessee, United States
Mayer Children's Hospital of Haifa
🇮🇱
Haifa, Israel
Schneider Children's Medical
🇮🇱
Petach-Tikva, Israel
Health & Research Centre
🇮🇳
Trivandrum, Kerala, India
The Safra Children's Hospital, The Chaim Sheba Medical Center
🇮🇱
Ramat-Gan, Israel
Medical Care & Research
🇲🇽
Merida, Yucatan, Mexico
Centro Especializado en Diabetes, Obesidad y Prevención de Enfermedades Cardiovasculares, S.C.
🇲🇽
Mexico, Distrito Federal, Mexico
Samodzielny Publiczny Szpital Kliniczny Nr1 we Wroclawiu
🇵🇱
Wroclaw, Poland
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Uniwersytecki Szpital Kliniczny Nr 4
🇵🇱
Łódź, Poland
S.C. Minimed S.R.L.
🇷🇴
Bacau, Romania
Institutul National De Diabet, Nutritie si Boli Metabolice
🇷🇴
Bucuresti, Romania
Spitalul Judetean de Urgenta Satu Mare
🇷🇴
Satu-Mare, Romania
Hospital y Clinica OCA / Monterrey International Research Center
🇲🇽
Monterrey, Nuevo León, Mexico
B. P. Poddar Hospital & Medical Research Limited
🇮🇳
Kolkata, West Bengal, India
Apollo Glenagles Hospital
🇮🇳
Kolkata, West Bengal, India
The E. Wolfson Medical Center
🇮🇱
Holon, Israel
DHL Research Centre
🇮🇳
Ahmedabad, Gujarat, India
Gandhi's Research Institute
🇮🇳
Nagpur, Maharashtra, India
Kharkiv Regional Clinical Children Hospital, Department of Endocrinology
🇺🇦
Kharkiv, Ukraine
Ukrainian Children Specialized Clinical Hospital
🇺🇦
Kyiv, Ukraine
Institute of Endocrinology and Metabolism named after V.Komisarenko of AMS Ukraine
🇺🇦
Kyiv, Ukraine
George Eliot Hospital NHS Trust
🇬🇧
Nuneaton, Warwickshire, United Kingdom
Grant Medical Foundation
🇮🇳
Pune, Maharashtra, India