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

Type 1 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00920582
• Other study ID #: CP-MGA031-03
• Status: Terminated
• Phase: Phase 3
• Start date: September 2009
• Est. completion date: July 2012

Study information

• Verified date: October 2023
• Source: MacroGenics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 254
• Est. completion date: July 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Biological:
• Teplizumab Herold Regimen
Full dose of teplizumab IV for 14 days, repeated at Week 26

Drug:
• Placebo
IV dosing daily for 14 days repeated at Week 26

Biological:
• Teplizumab 33.3% Herold Regimen
One third full dose of teplizumab IV for 14 days, repeated at Week 26
• Teplizumab Curtailed Herold Regimen
Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
MacroGenics	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Belgium,  Czechia,  Finland,  France,  Germany,  India,  Israel,  Italy,  Mexico,  Netherlands,  Poland,  Romania,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Mean Change From Baseline in HbA1c Between Teplizumab and Placebo		52 weeks after randomization
Secondary	The Change in Beta-cell Function as Measured by C-peptide Secretory Response Following a Mixed Meal		52 weeks after randomization
Secondary	The Change in Beta-cell Function as Measured by C-peptide Secretory Response Following a Mixed Meal		104 weeks after randomization
Secondary	Mean Number of Total, Major, Minor and Nocturnal Hypoglycemia Events	Number of hypoglycemic events by type per participant	Throughout the study up to 2 years
Secondary	Mean Number of Daily Insulin Injections		52 weeks after randomization
Secondary	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
Secondary	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
Secondary	The Mean HbA1c Change From Baseline		104 weeks after randomization
Secondary	Number of Participants With Adverse Events		throughout the study, up to 104 weeks
Secondary	Number of Participants With Serious Adverse Events		throughout the study, up to 104 weeks