The Protégé Study - Clinical Trial of MGA031 in Children and Adults With Recent-Onset Type 1 Diabetes Mellitus

NCT ID: NCT00385697

Last Updated: 2023-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 554 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-31
• Study Completion Date: 2011-08-31

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

Conditions

Type 1 Diabetes Mellitus

Keywords

Randomized; Double Blind; Parallel Group; Controlled Clinical Trial

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Double-blind Herold Regimen

Full dose of teplizumab IV for 14 days, repeated at Week 26

Group Type: EXPERIMENTAL

Teplizumab

Intervention Type: BIOLOGICAL

Daily IV dosing for 14 days, repeated at Week 26

Double-blind 33.3% Herold Regimen

One third full dose of teplizumab IV for 14 days, repeated at Week 26

Group Type: EXPERIMENTAL

Teplizumab

Intervention Type: BIOLOGICAL

Daily IV dosing for 14 days, repeated at Week 26

Double-blind Curtailed Herold Regimen

Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26

Group Type: EXPERIMENTAL

Teplizumab

Intervention Type: BIOLOGICAL

Daily IV dosing for 14 days, repeated at Week 26

Double-blind Placebo

Placebo IV dosing daily for 14 days repeated at Week 26

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Daily IV dosing for 14 days, repeated at Week 26

Open-label Herold Regimen

Full dose of teplizumab IV for 14 days, repeated at Week 26

Group Type: EXPERIMENTAL

Teplizumab

Intervention Type: BIOLOGICAL

Daily IV dosing for 14 days, repeated at Week 26

Interventions

Teplizumab

Daily IV dosing for 14 days, repeated at Week 26

Intervention Type: BIOLOGICAL

Placebo

Daily IV dosing for 14 days, repeated at Week 26

Intervention Type: DRUG

Other Intervention Names

MGA031

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)

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

MacroGenics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UAB School of Medicine

Birmingham, Alabama, United States

NEA Clinic

Jonesboro, Arkansas, United States

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Diabetes Medical Center of California

Northridge, California, United States

UCSF Medical Center

San Francisco, California, United States

University of Colorado Health Sciences Center

Aurora, Colorado, United States

Yale University

New Haven, Connecticut, United States

Christiana Care Research Institute

Newark, Delaware, United States

Richard Hays, MD

Wellington, Florida, United States

Atlanta Diabetes Associates

Atlanta, Georgia, United States

Humphrey Diabetes Center

Boise, Idaho, United States

Rocky Mountain Diabetes & Osteoporosis Center

Idaho Falls, Idaho, United States

Riley Hospital for Children

Indianapolis, Indiana, United States

University of Iowa Children's Hospital

Iowa City, Iowa, United States

Mid-America Diabetes Associates, PA

Wichita, Kansas, United States

Commonwealth Biomedical Research, LLC

Madisonville, Kentucky, United States

St. Agnes Hospital

Baltimore, Maryland, United States

Maryland Diabetes & Endocrine Associates

Rockville, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Baystate Medical Center

Springfield, Massachusetts, United States

Alzohaili Medical Consultants

Dearborn, Michigan, United States

The Children's Mercy Hospital

Kansas City, Missouri, United States

Creighton Diabetes Center

Omaha, Nebraska, United States

Saint Barnabas Medical Center

Livingston, New Jersey, United States

University of Medicine & Dentistry of NJ

New Brunswick, New Jersey, United States

Albany Medical Center

Albany, New York, United States

Schneider Children's Hospital

New Hyde Park, New York, United States

Joslin Diabetes Center

Syracuse, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

St. Mary Medical Center

Langhorne, Pennsylvania, United States

Sumter Medical Specialists

Sumter, South Carolina, United States

University Diabetes & Endocrine Consultants

Chattanooga, Tennessee, United States

Methodist Healthcare

Memphis, Tennessee, United States

Research Institute of Dallas

Dallas, Texas, United States

Spectra Research Center

McAllen, Texas, United States

Diabetes and Glandular Disease Research

San Antonio, Texas, United States

Endocrine Research Specialists

Ogden, Utah, United States

Pacific Northwest Research Institute

Seattle, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Alberta Children's Hospital

Calgary, Alberta, Canada

University of Manitoba

Winnipeg, Manitoba, Canada

University Health Sciences Centre

St. John's, Newfoundland and Labrador, Canada

Capital District Health Authority

Halifax, Nova Scotia, Canada

Oxford AIM Clinic

London, Ontario, Canada

Children's Hospital of Western

London, Ontario, Canada

FN Brno- Detska nemocnice

Brno, , Czechia

FN Hradec Kralove

Hradec Králové, , Czechia

Nemocnice Jihlava

Jihlava, , Czechia

FN Kralovske Vinohrady

Prague, , Czechia

Fakultni nemocnice v Motole

Prague, , Czechia

Masarykova nemocnice v Usti nad Labem

Ústí nad Labem, , Czechia

Tartu University Hospital

Puusepa, Tartu, Estonia

East Tallinn Central Hospital

Tallinn, , Estonia

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Medizinische Universitätsklinik Ulm

Ulm, Baden-Wurttemberg, Germany

Herz-und Diabetszentrum Nordrhein-Westfalen

Bad Oeynhausen, North Rhine-Westphalia, Germany

Charité-Hochschulmedizin Berlin

Berlin, , Germany

Universitatsklinik Giessen

Giessen, , Germany

Nizam's Institute of Medical Sciences

Hyderabad, Andhra Pradesh, India

King George Hospital

Visakhapatnam, Andhra Pradesh, India

Gujarat Endocrine Centre

Ahmedabad, Gujarat, India

DHL Research Centre

Ahmedabad, Gujarat, India

Bharti Research Institute of Diabetes & Endocrinology

Karnāl, Haryana, India

Bangalore Diabetes Centre

Bangalore, Karnataka, India

Diabetes Thyroid Hormone Research Institute PVT LTD

Indore, Madhya Pradesh, India

Diabetes Action Centre

Mumbai, Maharashtra, India

Gandhi Endocrinology and Diabetes Centre

Nagpur, Maharashtra, India

Endocrine Clinic

Nashik, Maharashtra, India

Grant Medical Foundation

Pune, Maharashtra, India

Fortis Escorts Hospital

Jaipur, Rajasthan, India

B.P.Poddar Hospital and Medical Research Ltd

Kolkata, West Bengal, India

Medwin Hospitals

Hyderabad, , India

Pushpawati Singhania Research Institute

New Delhi, , India

Soroka Medical Centre

Beersheba, , Israel

Hillel Yaffe Medical Center

Hadera, , Israel

Rambam Medical Centre

Haifa, , Israel

Wolfson Medical Centre

Holon, , Israel

National Centre for Childhood and Diabetes

Petah Tikva, , Israel

Chaim Sheba Medical Center

Ramat Gan, , Israel

P. Stradins Clinical University Hospital

Riga, , Latvia

Hospital CIMA Santa Engracia

San Pedro Garza García, Nuevo León, Mexico

Hospital Mexico-Americano

Guadalajara, , Mexico

Hospital General de Mexico

Mexico City, , Mexico

Hospital Central

San Luis Potosí City, , Mexico

Diabeter Center for Pediatric and Adolescent Diabetes Care and Research

Rotterdam, , Netherlands

Samodzielny Publiczny Szpital Kliniczny Akademi Medycznej w Bialymstoku

Bialystok, , Poland

Oddzial Diabetologiczny Klinika Pediatrii

Gdansk, , Poland

Wojewodzki Specjalistyczny Szpital Dzieciecy

Kielce, , Poland

Uniwersytecki Szpital Kliniczny

Lodz, , Poland

I. Szpital Miejski im. Dr. E. Sonnenberga w Lodzi

Lodz, , Poland

Powiatowy Zespot Szpitali w Olesnicy, Oddzial Chorob Wewnetrznych

Oleśnica, , Poland

Klinika Endokrynologii i Diabetologii Wieku Rozwojowego

Wroclaw, , Poland

S.C. Minimed S.R.L.

Bacau, , Romania

Institutul de Diabet

Bucharest, , Romania

Centrul Medical "Sanatatea ta"

Bucharest, , Romania

Spitulul Clinic Judetean de Urgenta Cluj

Cluj-Napoca, , Romania

Spitalul Clinic Judetean de Urgenta

Iași, , Romania

Spitalul Judetean Satu Mare

Satu Mare, , Romania

Hospital Universitari Dr. Josep Trueta de Girona

Girona, Gerona, Spain

Hospital Universitario Principe de Asturias

Alcalá de Henares, Madrid, Spain

Hospital Germans Trias i Pujol

Badalona, , Spain

Hospital Clinic I Provincial

Barcelona, , Spain

Fundacion Jimenez Diaz

Madrid, , Spain

Universitetssjukhuset i Linkoping

Linköping, , Sweden

Universitetssjukhuset i Lund

Lund, , Sweden

Sodersjukhuset AB

Stockholm, , Sweden

Donetsk Regional Children Clinical Hospital

Donetsk, , Ukraine

V. Danilevsky Institute of Endocrine Pathology Problems

Kharkiv, , Ukraine

Kharkiv Regional Clinical Children's Hospital

Kharkiv, , Ukraine

Ukrainian Scientific and Practical Center of Endocrine Surgery

Kyiv, , Ukraine

Ukranian Children Specialised Clinical Hospital

Kyiv, , Ukraine

Regional Clinical Endocrinological Dispensary

Vinnitsa, , Ukraine

Zaporizhzhya Regional Pediatric Hospital

Zaporizhzhya, , Ukraine

Addenbrookes Hospital

Cambridge, Cambridgeshire, United Kingdom

Royal Devon and Exeter Hospital

Exeter, Devon, United Kingdom

Countries

United States; Canada; Czechia; Estonia; Germany; India; Israel; Latvia; Mexico; Netherlands; Poland; Romania; Spain; Sweden; Ukraine; United Kingdom

References

Ajmal N, Bogart MC, Khan P, Max-Harry IM, Healy AM, Nunemaker CS. Identifying Promising Immunomodulators for Type 1 Diabetes (T1D) and Islet Transplantation. J Diabetes Res. 2024 Dec 20;2024:5151171. doi: 10.1155/jdr/5151171. eCollection 2024.

Reference Type: DERIVED

PMID: 39735417 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21719095 (View on PubMed)

Other Identifiers

CP-MGA031-01

Identifier Type: -

Identifier Source: org_study_id