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

Type 1 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00385697
• Other study ID #: CP-MGA031-01
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: October 2006
• Est. completion date: August 2011

Study information

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

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 554
• Est. completion date: August 2011
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 35 Years

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

Biological:
• Teplizumab
Daily IV dosing for 14 days, repeated at Week 26

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

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	Capital District Health Authority	Halifax	Nova Scotia
Canada	Children's Hospital of Western	London	Ontario
Canada	Oxford AIM Clinic	London	Ontario
Canada	University Health Sciences Centre	St. John's	Newfoundland and Labrador
Canada	University of Manitoba	Winnipeg	Manitoba
Czechia	FN Brno- Detska nemocnice	Brno
Czechia	FN Hradec Kralove	Hradec Kralove
Czechia	Nemocnice Jihlava	Jihlava
Czechia	Fakultni nemocnice v Motole	Praha
Czechia	FN Kralovske Vinohrady	Praha 10
Czechia	Masarykova nemocnice v Usti nad Labem	Usti nad Labem
Estonia	Tartu University Hospital	Puusepa	Tartu
Estonia	East Tallinn Central Hospital	Tallinn
Germany	Herz-und Diabetszentrum Nordrhein-Westfalen	Bad Oeynhausen	North Rhine-Westphalia
Germany	Charité-Hochschulmedizin Berlin	Berlin
Germany	Universitatsklinik Giessen	Giessen
Germany	Universitätsklinikum Heidelberg	Heidelberg	Baden-Wurttemberg
Germany	Medizinische Universitätsklinik Ulm	Ulm	Baden-Wurttemberg
India	DHL Research Centre	Ahmedabad	Gujarat
India	Gujarat Endocrine Centre	Ahmedabad	Gujarat
India	Bangalore Diabetes Centre	Bangalore	Karnataka
India	Medwin Hospitals	Hyderabad
India	Nizam's Institute of Medical Sciences	Hyderabad	Andhra Pradesh
India	Diabetes Thyroid Hormone Research Institute PVT LTD	Indore	Madhya Pradesh
India	Fortis Escorts Hospital	Jaipur	Rajasthan
India	Bharti Research Institute of Diabetes & Endocrinology	Karnal	Haryana
India	B.P.Poddar Hospital and Medical Research Ltd	Kolkata	West Bengal
India	Diabetes Action Centre	Mumbai	Maharashtra
India	Gandhi Endocrinology and Diabetes Centre	Nagpur	Maharashtra
India	Endocrine Clinic	Nashik	Maharashtra
India	Pushpawati Singhania Research Institute	New Delhi
India	Grant Medical Foundation	Pune	Maharashtra
India	King George Hospital	Visakhapatnam	Andhra Pradesh
Israel	Soroka Medical Centre	Beer Sheba
Israel	Hillel Yaffe Medical Center	Hadera
Israel	Rambam Medical Centre	Haifa
Israel	Wolfson Medical Centre	Holon
Israel	National Centre for Childhood and Diabetes	Petach Tikva
Israel	Chaim Sheba Medical Center	Ramat-Gan
Latvia	P. Stradins Clinical University Hospital	Riga
Mexico	Hospital Mexico-Americano	Guadalajara
Mexico	Hospital General de Mexico	Mexico City
Mexico	Hospital Central	San Luis Potosí
Mexico	Hospital CIMA Santa Engracia	San Pedro Garza García	Nuevo Leon
Netherlands	Diabeter Center for Pediatric and Adolescent Diabetes Care and Research	Rotterdam
Poland	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	Lódz
Poland	Powiatowy Zespot Szpitali w Olesnicy, Oddzial Chorob Wewnetrznych	Olesnica
Poland	Klinika Endokrynologii i Diabetologii Wieku Rozwojowego	Wroclaw
Romania	S.C. Minimed S.R.L.	Bacau
Romania	Institutul de Diabet	Bucharest
Romania	Centrul Medical "Sanatatea ta"	Bucuresti
Romania	Spitulul Clinic Judetean de Urgenta Cluj	Cluj-Napoca
Romania	Spitalul Clinic Judetean de Urgenta	Iasi
Romania	Spitalul Judetean Satu Mare	Satu Mare
Spain	Hospital Universitario Principe de Asturias	Alcala de Henares	Madrid
Spain	Hospital Germans Trias i Pujol	Badalona
Spain	Hospital Clinic I Provincial	Barcelona
Spain	Hospital Universitari Dr. Josep Trueta de Girona	Girona	Gerona
Spain	Fundacion Jimenez Diaz	Madrid
Sweden	Universitetssjukhuset i Linkoping	Linkoping
Sweden	Universitetssjukhuset i Lund	Lund
Sweden	Sodersjukhuset AB	Stockholm
Ukraine	Donetsk Regional Children Clinical Hospital	Donetsk
Ukraine	Kharkiv Regional Clinical Children's Hospital	Kharkiv
Ukraine	V. Danilevsky Institute of Endocrine Pathology Problems	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
United Kingdom	Addenbrookes Hospital	Cambridge	Cambridgeshire
United Kingdom	Royal Devon and Exeter Hospital	Exeter	Devon
United States	Albany Medical Center	Albany	New York
United States	Atlanta Diabetes Associates	Atlanta	Georgia
United States	University of Colorado Health Sciences Center	Aurora	Colorado
United States	St. Agnes Hospital	Baltimore	Maryland
United States	UAB School of Medicine	Birmingham	Alabama
United States	Humphrey Diabetes Center	Boise	Idaho
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University Diabetes & Endocrine Consultants	Chattanooga	Tennessee
United States	Cleveland Clinic	Cleveland	Ohio
United States	Research Institute of Dallas	Dallas	Texas
United States	Alzohaili Medical Consultants	Dearborn	Michigan
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	NEA Clinic	Jonesboro	Arkansas
United States	The Children's Mercy Hospital	Kansas City	Missouri
United States	St. Mary Medical Center	Langhorne	Pennsylvania
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Commonwealth Biomedical Research, LLC	Madisonville	Kentucky
United States	Spectra Research Center	McAllen	Texas
United States	Methodist Healthcare	Memphis	Tennessee
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Medicine & Dentistry of NJ	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
United States	Schneider Children's Hospital	New Hyde Park	New York
United States	Christiana Care Research Institute	Newark	Delaware
United States	Diabetes Medical Center of California	Northridge	California
United States	Endocrine Research Specialists	Ogden	Utah
United States	Creighton Diabetes Center	Omaha	Nebraska
United States	Maryland Diabetes & Endocrine Associates	Rockville	Maryland
United States	Diabetes and Glandular Disease Research	San Antonio	Texas
United States	UCSF Medical Center	San Francisco	California
United States	Pacific Northwest Research Institute	Seattle	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Sumter Medical Specialists	Sumter	South Carolina
United States	Joslin Diabetes Center	Syracuse	New York
United States	Richard Hays, MD	Wellington	Florida
United States	Mid-America Diabetes Associates, PA	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
MacroGenics	Eli Lilly and Company

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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%.	This is a composite endpoint is based on the proportion of subjects who have both a total daily insulin dose <0.5 U/Kg/day and an HbAlc level 6.5% at 52 weeks after randomization.	52 weeks after randomization
Primary	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%.	This is a composite endpoint based on the proportion of subjects who have both a total daily insulin dose <0.5 U/Kg/day and an HbAlc level 6.5%	52 weeks after first dose
Primary	Mean HbA1c Change From Baseline in Segment 2	Comparison among study treatments of average change from baseline HbA1C. This endpoint will be assessed in a hierarchical manner only if the composite primary endpoint shows a statistically significant difference between arms	52 weeks after randomization
Primary	Mean HbA1c Change From Baseline in Segment 1	The average change in HbA1c levels after dosing.	52 weeks after first dose
Secondary	Change From Baseline in C-peptide Area Under the Curve (AUC) in Segment 2	Comparison among study treatments on the AUC of C-peptide secretory responses following a mixed meal eaten by the subject	104 weeks after randomization
Secondary	Change From Baseline in C-peptide AUC in Segment 1	AUC of C-peptide secretory responses following a mixed meal eaten by the subject	104 weeks after first dose
Secondary	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%	Comparison among study treatments of a composite endpoint based on the proportion of subjects who have both a total daily insulin dose <0.5 U/Kg/day and an HbAlc level 6.5%.	104 weeks after randomization
Secondary	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%	Comparison among study treatments of a composite endpoint based on the proportion of subjects who have both a total daily insulin dose <0.5 U/Kg/day and an HbAlc level 6.5%.	104 weeks after first dose
Secondary	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%.	Comparison among study treatments of a composite endpoint based on the proportion of subjects who have both a total daily insulin dose <0.5 U/Kg/day and an HbAlc level 7.0%.	at 52 weeks after randomization
Secondary	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%.	Composite endpoint based on the proportion of subjects who have both a total daily insulin dose <0.5 U/Kg/day and an HbAlc level 7.0%.	52 weeks after first dose
Secondary	Mean HbA1c Change From Baseline in Segment 2	Comparison among study treatments of the average change from baseline in HbA1c.	at 104 weeks after randomization
Secondary	Mean HbA1c Change From Baseline in Segment 1	Comparison among study treatments of the average change from baseline in HbA1c.	104 weeks after first dose