Clinical trial NCT00385697: The Protégé Study - Clinical Trial of MGA031 in Children and Adults With Recent-Onset Type 1 Diabetes Mellitus
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Type 1 Diabetes Mellitus
Keywords: Randomized
Double Blind
Parallel Group
Controlled Clinical Trial
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2006-10-11
Enrollment: 554
Sex: ALL
Minimum age (years): 8
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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)

Primary outcomes:
measure: 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%.
timeFrame: 52 weeks after randomization
measure: 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%.
timeFrame: 52 weeks after first dose
measure: Mean HbA1c Change From Baseline in Segment 2
timeFrame: 52 weeks after randomization
measure: Mean HbA1c Change From Baseline in Segment 1
timeFrame: 52 weeks after first dose
Secondary outcomes:
measure: Change From Baseline in C-peptide Area Under the Curve (AUC) in Segment 2
timeFrame: 104 weeks after randomization
measure: Change From Baseline in C-peptide AUC in Segment 1
timeFrame: 104 weeks after first dose
measure: 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%
timeFrame: 104 weeks after randomization
measure: 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%
timeFrame: 104 weeks after first dose
measure: 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%.
timeFrame: at 52 weeks after randomization
measure: 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%.
timeFrame: 52 weeks after first dose
measure: Mean HbA1c Change From Baseline in Segment 2
timeFrame: at 104 weeks after randomization
measure: Mean HbA1c Change From Baseline in Segment 1
timeFrame: 104 weeks after first dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB School of Medicine
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: Northridge
country: United States
facility: Diabetes Medical Center of California
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
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: Boise
country: United States
facility: Humphrey Diabetes Center
state: Idaho
city: Idaho Falls
country: United States
facility: Rocky Mountain Diabetes & Osteoporosis Center
state: Idaho
city: Indianapolis
country: United States
facility: Riley Hospital for Children
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, PA
state: Kansas
city: Madisonville
country: United States
facility: Commonwealth Biomedical Research, LLC
state: Kentucky
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: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Dearborn
country: United States
facility: Alzohaili Medical Consultants
state: Michigan
city: Kansas City
country: United States
facility: The Children's Mercy Hospital
state: Missouri
city: Omaha
country: United States
facility: Creighton Diabetes Center
state: Nebraska
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: University of Medicine & Dentistry of NJ
state: New Jersey
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: New Hyde Park
country: United States
facility: Schneider Children's Hospital
state: New York
city: Syracuse
country: United States
facility: Joslin Diabetes Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Langhorne
country: United States
facility: St. Mary Medical Center
state: Pennsylvania
city: Sumter
country: United States
facility: Sumter Medical Specialists
state: South Carolina
city: Chattanooga
country: United States
facility: University Diabetes & Endocrine Consultants
state: Tennessee
city: Memphis
country: United States
facility: Methodist Healthcare
state: Tennessee
city: Dallas
country: United States
facility: Research Institute of Dallas
state: Texas
city: McAllen
country: United States
facility: Spectra Research Center
state: Texas
city: San Antonio
country: United States
facility: Diabetes and Glandular Disease Research
state: Texas
city: Ogden
country: United States
facility: Endocrine Research Specialists
state: Utah
city: Seattle
country: United States
facility: Pacific Northwest Research Institute
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: St. John's
country: Canada
facility: University Health Sciences Centre
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Capital District Health Authority
state: Nova Scotia
city: London
country: Canada
facility: Oxford AIM Clinic
state: Ontario
city: London
country: Canada
facility: Children's Hospital of Western
state: Ontario
city: Brno
country: Czechia
facility: FN Brno- Detska nemocnice
city: Hradec Kralove
country: Czechia
facility: FN Hradec Kralove
city: Jihlava
country: Czechia
facility: Nemocnice Jihlava
city: Praha 10
country: Czechia
facility: FN Kralovske Vinohrady
city: Praha
country: Czechia
facility: Fakultni nemocnice v Motole
city: Usti nad Labem
country: Czechia
facility: Masarykova nemocnice v Usti nad Labem
city: Puusepa
country: Estonia
facility: Tartu University Hospital
state: Tartu
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
state: Baden-Wurttemberg
city: Ulm
country: Germany
facility: Medizinische Universitätsklinik Ulm
state: Baden-Wurttemberg
city: Bad Oeynhausen
country: Germany
facility: Herz-und Diabetszentrum Nordrhein-Westfalen
state: North Rhine-Westphalia
city: Berlin
country: Germany
facility: Charité-Hochschulmedizin Berlin
city: Giessen
country: Germany
facility: Universitatsklinik Giessen
city: Hyderabad
country: India
facility: Nizam's Institute of Medical Sciences
state: Andhra Pradesh
city: Visakhapatnam
country: India
facility: King George Hospital
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Gujarat Endocrine Centre
state: Gujarat
city: Ahmedabad
country: India
facility: DHL Research Centre
state: Gujarat
city: Karnal
country: India
facility: Bharti Research Institute of Diabetes & Endocrinology
state: Haryana
city: Bangalore
country: India
facility: Bangalore Diabetes Centre
state: Karnataka
city: Indore
country: India
facility: Diabetes Thyroid Hormone Research Institute PVT LTD
state: Madhya Pradesh
city: Mumbai
country: India
facility: Diabetes Action Centre
state: Maharashtra
city: Nagpur
country: India
facility: Gandhi Endocrinology and Diabetes Centre
state: Maharashtra
city: Nashik
country: India
facility: Endocrine Clinic
state: Maharashtra
city: Pune
country: India
facility: Grant Medical Foundation
state: Maharashtra
city: Jaipur
country: India
facility: Fortis Escorts Hospital
state: Rajasthan
city: Kolkata
country: India
facility: B.P.Poddar Hospital and Medical Research Ltd
state: West Bengal
city: Hyderabad
country: India
facility: Medwin Hospitals
city: New Delhi
country: India
facility: Pushpawati Singhania Research Institute
city: Beer Sheba
country: Israel
facility: Soroka Medical Centre
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Centre
city: Holon
country: Israel
facility: Wolfson Medical Centre
city: Petach Tikva
country: Israel
facility: National Centre for Childhood and Diabetes
city: Ramat-Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Riga
country: Latvia
facility: P. Stradins Clinical University Hospital
city: San Pedro Garza García
country: Mexico
facility: Hospital CIMA Santa Engracia
state: Nuevo Leon
city: Guadalajara
country: Mexico
facility: Hospital Mexico-Americano
city: Mexico City
country: Mexico
facility: Hospital General de Mexico
city: San Luis Potosí
country: Mexico
facility: Hospital Central
city: Rotterdam
country: Netherlands
facility: Diabeter Center for Pediatric and Adolescent Diabetes Care and Research
city: Bialystok
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Akademi Medycznej w Bialymstoku
city: Gdansk
country: Poland
facility: Oddzial Diabetologiczny Klinika Pediatrii
city: Kielce
country: Poland
facility: Wojewodzki Specjalistyczny Szpital Dzieciecy
city: Lodz
country: Poland
facility: Uniwersytecki Szpital Kliniczny
city: Olesnica
country: Poland
facility: Powiatowy Zespot Szpitali w Olesnicy, Oddzial Chorob Wewnetrznych
city: Wroclaw
country: Poland
facility: Klinika Endokrynologii i Diabetologii Wieku Rozwojowego
city: Łódź
country: Poland
facility: I. Szpital Miejski im. Dr. E. Sonnenberga w Lodzi
city: Bacau
country: Romania
facility: S.C. Minimed S.R.L.
city: Bucharest
country: Romania
facility: Institutul de Diabet
city: Bucuresti
country: Romania
facility: Centrul Medical "Sanatatea ta"
city: Cluj-Napoca
country: Romania
facility: Spitulul Clinic Judetean de Urgenta Cluj
city: Iasi
country: Romania
facility: Spitalul Clinic Judetean de Urgenta
city: Satu Mare
country: Romania
facility: Spitalul Judetean Satu Mare
city: Girona
country: Spain
facility: Hospital Universitari Dr. Josep Trueta de Girona
state: Gerona
city: Alcala de Henares
country: Spain
facility: Hospital Universitario Principe de Asturias
state: Madrid
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Linkoping
country: Sweden
facility: Universitetssjukhuset i Linkoping
city: Lund
country: Sweden
facility: Universitetssjukhuset i Lund
city: Stockholm
country: Sweden
facility: Sodersjukhuset AB
city: Donetsk
country: Ukraine
facility: Donetsk Regional Children Clinical Hospital
city: Kharkiv
country: Ukraine
facility: V. Danilevsky Institute of Endocrine Pathology Problems
city: Kharkiv
country: Ukraine
facility: Kharkiv Regional Clinical Children's Hospital
city: Kyiv
country: Ukraine
facility: Ukrainian Scientific and Practical Center of Endocrine Surgery
city: Kyiv
country: Ukraine
facility: Ukranian Children Specialised Clinical Hospital
city: Vinnitsa
country: Ukraine
facility: Regional Clinical Endocrinological Dispensary
city: Zaporizhzhya
country: Ukraine
facility: Zaporizhzhya Regional Pediatric Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
state: Cambridgeshire
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: Devon
Study officials:
References:
citation: 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.