Clinical trial NCT00920582: Protege Encore Study- Clinical Trial of Teplizumab (MGA031) in Children and Adults With Recent-Onset Type 1 Diabetes Mellitus
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2009-06-15
Enrollment: 254
Sex: ALL
Minimum age (years): 8
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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%.
timeFrame: 52 weeks after randomization
measure: Mean Change From Baseline in HbA1c Between Teplizumab and Placebo
timeFrame: 52 weeks after randomization
Secondary outcomes:
measure: The Change in Beta-cell Function as Measured by C-peptide Secretory Response Following a Mixed Meal
timeFrame: 52 weeks after randomization
measure: The Change in Beta-cell Function as Measured by C-peptide Secretory Response Following a Mixed Meal
timeFrame: 104 weeks after randomization
measure: Mean Number of Total, Major, Minor and Nocturnal Hypoglycemia Events
timeFrame: Throughout the study up to 2 years
measure: Mean Number of Daily Insulin Injections
timeFrame: 52 weeks after randomization
measure: 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%.
timeFrame: 104 weeks after randomization
measure: The Proportion of Subjects Who Have Both a Total Daily Insulin Dose < 0.5 U/Kg/Day and Hemoglobin A1c (HbA1c) Level < 7.0%
timeFrame: 52 weeks after randomization
measure: The Mean HbA1c Change From Baseline
timeFrame: 104 weeks after randomization
measure: Number of Participants With Adverse Events
timeFrame: throughout the study, up to 104 weeks
measure: Number of Participants With Serious Adverse Events
timeFrame: throughout the study, up to 104 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Jonesboro
country: United States
facility: NEA Clinic
state: Arkansas
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Costa Mesa
country: United States
facility: Clinical Innovations Inc. Research Facility
state: California
city: Los Angeles
country: United States
facility: Axis Clinical Trials
state: California
city: Orange
country: United States
facility: Diabetes Associates Medical Group, Inc
state: California
city: Riverside
country: United States
facility: Clinical Innovations, Inc.
state: California
city: San Diego
country: United States
facility: San Diego Clinical Trials
state: California
city: Ventura
country: United States
facility: Ronald Chochinov Md Inc
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Newark
country: United States
facility: Christiana Care Research Institute
state: Delaware
city: Wellington
country: United States
facility: Richard Hays, MD
state: Florida
city: Atlanta
country: United States
facility: Atlanta Diabetes Associates
state: Georgia
city: Chicago
country: United States
facility: John H Stoger Jr. Hospital of Cook County, Cook County Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Children's Hospital
state: Iowa
city: Wichita
country: United States
facility: Mid-America Diabetes Associates
state: Kansas
city: Baltimore
country: United States
facility: St. Agnes Hospital
state: Maryland
city: Rockville
country: United States
facility: Maryland Diabetes & Endocrine Associates
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Dearborn
country: United States
facility: Alzohaili Medical Consultants
state: Michigan
city: Saint Paul
country: United States
facility: Children's Hospitals and Clinics of Minnesota
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri - Columbia, Cosmopolitan Diabetes and Endocrinology
state: Missouri
city: Kansas City
country: United States
facility: The Children's Mercy Hospital
state: Missouri
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Cooperstown
country: United States
facility: Bassett Healthcare
state: New York
city: Greenville
country: United States
facility: East Carolina University, Brody School of Medicine
state: North Carolina
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Greenville
country: United States
facility: GHS Pediatric Endocrinology
state: South Carolina
city: Bartlett
country: United States
facility: AM Diabetes & Endocrinology Center
state: Tennessee
city: Chattanooga
country: United States
facility: University Diabetes & Endocrine Consultants
state: Tennessee
city: Memphis
country: United States
facility: LeBonheur Children's Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Research Institute of Dallas
state: Texas
city: Houston
country: United States
facility: Southwest Clinical Trials
state: Texas
city: Houston
country: United States
facility: Houston Center for Clinical Research
state: Texas
city: Irving
country: United States
facility: Medical & Surgical Clinic of Irving
state: Texas
city: San Antonio
country: United States
facility: InVisions Consultants, LLC
state: Texas
city: San Antonio
country: United States
facility: Diabetes and Glandular Disease Research Associates, PA
state: Texas
city: Ogden
country: United States
facility: Endocrine Research Specialists
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University-Division of Pediatric Endocrinology & Metabolism
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
state: Antwerp
city: Arlon
country: Belgium
facility: Cliniques du Sud Luxembourg - Vivalia
city: Brno
country: Czechia
facility: I. Detska interni klinika,Fakultni nemocnice Brno Detska nemocnice
city: Praha
country: Czechia
facility: Klinika deti a dorostu FN Kralovske Vinohrady
city: Praha
country: Czechia
facility: Centrum diabetologie, Institut klinicke a experimentalni mediciny
city: Praha
country: Czechia
facility: Pediatricka klinika UK 2.LF a FN Motol, Fakultni nemocnice v Motole
city: Usti nad Labem
country: Czechia
facility: Detska klinika, Masarykova nemocnice v Usti nad Labem, o.z.
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Mikkeli
country: Finland
facility: Central Hospital of Mikkeli
city: Oulu
country: Finland
facility: Oulu University Hospital
city: Besançon
country: France
facility: CHU de Besançon
city: Brest
country: France
facility: CHU de Brest Hôpital de la Cavale Blanche
city: Corbeil-Essonnes
country: France
facility: Centre Hospitalier Sud Francilien
city: Pessac
country: France
facility: CHU de Bordeaux
city: Reims
country: France
facility: CHU de Reims
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg Hôpital Civil
city: Bad Nauheim
country: Germany
facility: Diabetes-Klinik Bad Nauheim GmbH
city: Bad Oeynhausen
country: Germany
facility: Herz und Diabeteszentrum Nordrhein-Westfallen
city: Berlin
country: Germany
facility: Charite, Campus Benjamin Franklin
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Giessen
country: Germany
facility: Universitatsklinik Giessen
city: Hamburg
country: Germany
facility: Asklepios Westklinikum Hamburg
city: Hannover
country: Germany
facility: Kinderkrankenhaus auf der Bult
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
city: Hyderabad
country: India
facility: Medwin Hospitals
state: Andhra Pradesh
city: Visakhapatnam
country: India
facility: King George Hospital
state: Andhra Pradesh
city: New Delhi
country: India
facility: Maulana Azad Medical College and Associated Hospitals
state: Delhi
city: Ahmedabad
country: India
facility: DHL Research Centre
state: Gujarat
city: Bangalore
country: India
facility: Bangalore Diabetes Centre
state: Karnataka
city: Trivandrum
country: India
facility: Health & Research Centre
state: Kerala
city: Nagpur
country: India
facility: Gandhi's Research Institute
state: Maharashtra
city: Pune
country: India
facility: Grant Medical Foundation
state: Maharashtra
city: Pune
country: India
facility: KEM Hospital Research Center
state: Maharashtra
city: Bhubaneswar
country: India
facility: Kalinga Hospital Limited
state: Orissa
city: Madhya
country: India
facility: Diabetes-Thyroid-Hormone Research Institute Pvt. Ltd.
state: Pradesh
city: Ludhiana
country: India
facility: Dayanand Medical College and Hospital
state: Punjab
city: Jaipur
country: India
facility: Fortis Escorts Hospital
state: Rajasthan
city: Ghaziabad
country: India
facility: Hormone Care & Research Center
state: Uttar Pradesh
city: Kolkata
country: India
facility: B. P. Poddar Hospital & Medical Research Limited
state: West Bengal
city: Kolkata
country: India
facility: Apollo Glenagles Hospital
state: West Bengal
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center
city: Haifa
country: Israel
facility: Mayer Children's Hospital of Haifa
city: Holon
country: Israel
facility: The E. Wolfson Medical Center
city: Petach-Tikva
country: Israel
facility: Schneider Children's Medical
city: Ramat-Gan
country: Israel
facility: The Safra Children's Hospital, The Chaim Sheba Medical Center
city: Modena
country: Italy
facility: Struttura Complessa di Pediatria, Azienda Ospedaliero-Universitaria di Modena,
city: Pisa
country: Italy
facility: U.O. di Malattie del Metabolismo
city: Pisa
country: Italy
facility: U.O. di Malattie Metaboliche e Diabetologia
city: Monterrey
country: Mexico
facility: Hospital y Clinica OCA / Monterrey International Research Center
state: Nuevo León
city: Merida
country: Mexico
facility: Medical Care & Research
state: Yucatan
city: Mexico, Distrito Federal
country: Mexico
facility: Centro Especializado en Diabetes, Obesidad y Prevención de Enfermedades Cardiovasculares, S.C.
city: Rotterdam
country: Netherlands
facility: Stichting Diabeter
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Kielce
country: Poland
facility: Wojewódzki Specjalistyczny Szpital Dzieciecy
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie-Filia
city: Wroclaw
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr1 we Wroclawiu
city: Łódź
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Uniwersytecki Szpital Kliniczny Nr 4
city: Bacau
country: Romania
facility: S.C. Minimed S.R.L.
city: Bucuresti
country: Romania
facility: Institutul National De Diabet, Nutritie si Boli Metabolice
city: Satu-Mare
country: Romania
facility: Spitalul Judetean de Urgenta Satu Mare
city: Alcala de Henares
country: Spain
facility: Hospital Universitario Principe de Asturias
city: Girona
country: Spain
facility: Hospital Dr. Josep Trueta
city: Donetsk
country: Ukraine
facility: Donetsk Regional Children Clinical Hospital
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Clinical Hospital
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk State Regional Pediatric Clinical Hospital
city: Kharkiv
country: Ukraine
facility: Kharkiv Regional Clinical Children Hospital, Department of Endocrinology
city: Kyiv
country: Ukraine
facility: Ukrainian Children Specialized Clinical Hospital
city: Kyiv
country: Ukraine
facility: Institute of Endocrinology and Metabolism named after V.Komisarenko of AMS Ukraine
city: Vinnitsa
country: Ukraine
facility: Regional Clinical Endocrinology Dispensary of MoH Ukraine
city: Nuneaton
country: United Kingdom
facility: George Eliot Hospital NHS Trust
state: Warwickshire
city: Bristol
country: United Kingdom
facility: University of Bristol Henery Wellcome laboratories for Integrative Neuroscience and Endocrinology,
city: Liverpool
country: United Kingdom
facility: Aintree University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: Kings College, Clinical Research Unit, Department of Diabetes and Endocrinology
city: Nottingham
country: United Kingdom
facility: Queens Medical Centre, Diabetes and Endocrinology Unit
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital NHS Foundation Trust
Study officials:
References: