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Type 1 Diabetes MellitusPhase 2/3NCT00385697

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

A Phase 2/3 study testing Teplizumab in people with Type 1 Diabetes Mellitus, run by MacroGenics at 115 sites in 16 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 8 to 35 years
Conditions the study is for
Type 1 Diabetes Mellitus
What is being tested?
Teplizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
554 participants
Where
115 sitesin 16 countries
Study dates
Oct 2006to Aug 2011
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 8 to 35 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Subjects must meet all of the following criteria:
  • 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.
  • Diagnosis of type 1 diabetes mellitus, according to the American Diabetes Association (ADA) criteria
  • Requirement for injected insulin therapy
  • Have a detectable fasting or stimulated C-peptide level (above the lower limit of detection of the assay)
  • One positive result on testing for any of the following antibodies:
Show all 15Show fewer
  • islet-cell autoantibodies (ICA512/IA-2),
  • glutamic acid decarboxylase autoantibodies, or
  • insulin autoantibodies (if present during first 2 weeks, but not beyond 2 weeks, of insulin treatment)
  • Male or female
  • 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
  • Body weight ≥ 36 kg

Who cannot join

  • Subjects must have none of the following:
  • 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
  • Participation in any type of therapeutic drug or vaccine clinical trial within the 12 weeks before enrollment or randomization
  • Any medical condition that, in the opinion of the investigator, would interfere with safe completion of the trial
  • Pregnant or lactating females
  • Prior murine OKT®3 treatment at any time before enrollment or randomization
Show all 20Show fewer
  • Current or planned therapy with exenatide or any other agents that stimulate pancreatic beta cell regeneration or insulin secretion
  • Current or planned therapy with inhaled insulin
  • 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
  • History of epilepsy, cancer, cystic fibrosis, sickle cell anemia, neuropathy, peripheral vascular disease or cerebrovascular disease
  • Newly diagnosed hypothyroidism (not currently being treated but which, in the opinion of the investigator, should be treated) or active Graves' disease
  • Eczema, asthma or severe atopic disease requiring treatment within the 12 weeks before enrollment or randomization
  • Evidence of active infection, such as fever ≥ 38.0 degrees Celsius (100.5 degrees Fahrenheit)
  • Known or suspected infection with human immunodeficiency virus (HIV)
  • Evidence of active hepatitis B (HBV) or hepatitis C virus (HCV)
  • Evidence of active or latent tuberculosis
  • 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.
  • Any infectious mononucleosis-like illness within the 6 months before enrollment or randomization
  • Serologic and clinical evidence of acute infection with Epstein-Barr virus (EBV)
  • Serologic evidence of acute infection with cytomegalovirus (CMV)

Trial locations and contacts

115 sites in 16 countries.

115 sites in 16 countries

United States39 sites

  • Albany Medical Center

    Albany, New York, 12208

  • Atlanta Diabetes Associates

    Atlanta, Georgia, 30309

  • University of Colorado Health Sciences Center

    Aurora, Colorado, 80045

  • St. Agnes Hospital

    Baltimore, Maryland, 21229

  • UAB School of Medicine

    Birmingham, Alabama, 35294

  • Humphrey Diabetes Center

    Boise, Idaho, 87702

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University Diabetes & Endocrine Consultants

    Chattanooga, Tennessee, 37403

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Research Institute of Dallas

    Dallas, Texas, 75231

  • Alzohaili Medical Consultants

    Dearborn, Michigan, 48126

  • Rocky Mountain Diabetes & Osteoporosis Center

    Idaho Falls, Idaho, 83404

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • University of Iowa Children's Hospital

    Iowa City, Iowa, 52242-1083

  • NEA Clinic

    Jonesboro, Arkansas, 72401

  • The Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • St. Mary Medical Center

    Langhorne, Pennsylvania, 19047

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202

  • Saint Barnabas Medical Center

    Livingston, New Jersey, 07039

  • Commonwealth Biomedical Research, LLC

    Madisonville, Kentucky, 42431

  • Spectra Research Center

    McAllen, Texas, 78503

  • Methodist Healthcare

    Memphis, Tennessee, 38104

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • University of Medicine & Dentistry of NJ

    New Brunswick, New Jersey, 08901

  • Yale University

    New Haven, Connecticut, 06519

  • Schneider Children's Hospital

    New Hyde Park, New York, 11040

  • Christiana Care Research Institute

    Newark, Delaware, 19713

  • Diabetes Medical Center of California

    Northridge, California, 91325

  • Endocrine Research Specialists

    Ogden, Utah, 84403

  • Creighton Diabetes Center

    Omaha, Nebraska, 68131

  • Maryland Diabetes & Endocrine Associates

    Rockville, Maryland, 20852

  • Diabetes and Glandular Disease Research

    San Antonio, Texas, 78229

  • UCSF Medical Center

    San Francisco, California, 94143

  • Pacific Northwest Research Institute

    Seattle, Washington, 98122

  • Baystate Medical Center

    Springfield, Massachusetts, 01199

  • Sumter Medical Specialists

    Sumter, South Carolina, 29150

  • Joslin Diabetes Center

    Syracuse, New York, 13214

  • Richard Hays, MD

    Wellington, Florida, 33414

  • Mid-America Diabetes Associates, PA

    Wichita, Kansas, 67211

Other trials in United States

India15 sites

  • Gujarat Endocrine Centre

    Ahmedabad, Gujarat, 380006

  • DHL Research Centre

    Ahmedabad, Gujarat, 380015

  • Bangalore Diabetes Centre

    Bangalore, Karnataka, 560043

  • Nizam's Institute of Medical Sciences

    Hyderabad, Andhra Pradesh, 500082

  • Medwin Hospitals

    Hyderabad, 500001

  • Diabetes Thyroid Hormone Research Institute PVT LTD

    Indore, Madhya Pradesh, 452001

  • Fortis Escorts Hospital

    Jaipur, Rajasthan, 302017

  • Bharti Research Institute of Diabetes & Endocrinology

    Karnāl, Haryana, 132001

  • B.P.Poddar Hospital and Medical Research Ltd

    Kolkata, West Bengal, 700053

  • Diabetes Action Centre

    Mumbai, Maharashtra, 400067

  • Gandhi Endocrinology and Diabetes Centre

    Nagpur, Maharashtra, 440010

  • Endocrine Clinic

    Nashik, Maharashtra, 422013

  • Pushpawati Singhania Research Institute

    New Delhi, 110017

  • Grant Medical Foundation

    Pune, Maharashtra, 411001

  • King George Hospital

    Visakhapatnam, Andhra Pradesh, 530002

Other trials in India

Poland7 sites

  • Samodzielny Publiczny Szpital Kliniczny Akademi Medycznej w Bialymstoku

    Bialystok, 15-276

  • Oddzial Diabetologiczny Klinika Pediatrii

    Gdansk, 80-952

  • Wojewodzki Specjalistyczny Szpital Dzieciecy

    Kielce, 25-734

  • Uniwersytecki Szpital Kliniczny

    Lodz, 91-738

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

    Lodz, 92115

  • Powiatowy Zespot Szpitali w Olesnicy, Oddzial Chorob Wewnetrznych

    Oleśnica, 56400

  • Klinika Endokrynologii i Diabetologii Wieku Rozwojowego

    Wroclaw, 51-376

Other trials in Poland

Ukraine7 sites

  • Donetsk Regional Children Clinical Hospital

    Donetsk, 83052

  • V. Danilevsky Institute of Endocrine Pathology Problems

    Kharkiv, 61070

  • Kharkiv Regional Clinical Children's Hospital

    Kharkiv, 61093

  • Ukrainian Scientific and Practical Center of Endocrine Surgery

    Kyiv, 02175

  • Ukranian Children Specialised Clinical Hospital

    Kyiv, 02175

  • Regional Clinical Endocrinological Dispensary

    Vinnitsa, 21010

  • Zaporizhzhya Regional Pediatric Hospital

    Zaporizhzhya, 69035

Other trials in Ukraine

Canada6 sites

  • Alberta Children's Hospital

    Calgary, Alberta, T3B 6A8

  • Capital District Health Authority

    Halifax, Nova Scotia, B3H2YN

  • Oxford AIM Clinic

    London, Ontario, N6A 5R9

  • Children's Hospital of Western

    London, Ontario, N6A5W9

  • University Health Sciences Centre

    St. John's, Newfoundland and Labrador, A1B3V6

  • University of Manitoba

    Winnipeg, Manitoba, R3E0Z2

Other trials in Canada

Czechia6 sites

  • FN Brno- Detska nemocnice

    Brno, 62500

  • FN Hradec Kralove

    Hradec Králové, 50005

  • Nemocnice Jihlava

    Jihlava, 58633

  • FN Kralovske Vinohrady

    Prague, 10034

  • Fakultni nemocnice v Motole

    Prague, 150 06

  • Masarykova nemocnice v Usti nad Labem

    Ústí nad Labem, 40113

Other trials in Czechia

Israel6 sites

  • Soroka Medical Centre

    Beersheba, 84101

  • Hillel Yaffe Medical Center

    Hadera, 38100

  • Rambam Medical Centre

    Haifa, 31096

  • Wolfson Medical Centre

    Holon, 58100

  • National Centre for Childhood and Diabetes

    Petah Tikva, 49202

  • Chaim Sheba Medical Center

    Ramat Gan, 56261

Other trials in Israel

Romania6 sites

  • S.C. Minimed S.R.L.

    Bacau, 600164

  • Institutul de Diabet

    Bucharest, 020045

  • Centrul Medical "Sanatatea ta"

    Bucharest, 20725

  • Spitulul Clinic Judetean de Urgenta Cluj

    Cluj-Napoca, 400006

  • Spitalul Clinic Judetean de Urgenta

    Iași, 700111

  • Spitalul Judetean Satu Mare

    Satu Mare, 440055

Other trials in Romania

Germany5 sites

  • Herz-und Diabetszentrum Nordrhein-Westfalen

    Bad Oeynhausen, North Rhine-Westphalia, 32545

  • Charité-Hochschulmedizin Berlin

    Berlin, 12200

  • Universitatsklinik Giessen

    Giessen, 35392

  • Universitätsklinikum Heidelberg

    Heidelberg, Baden-Wurttemberg, 69120

  • Medizinische Universitätsklinik Ulm

    Ulm, Baden-Wurttemberg, 89070

Other trials in Germany

Spain5 sites

  • Hospital Universitario Principe de Asturias

    Alcalá de Henares, Madrid, 28805

  • Hospital Germans Trias i Pujol

    Badalona, 8916

  • Hospital Clinic I Provincial

    Barcelona, 8036

  • Hospital Universitari Dr. Josep Trueta de Girona

    Girona, Gerona, 17007

  • Fundacion Jimenez Diaz

    Madrid, 28040

Other trials in Spain

Mexico4 sites

  • Hospital Mexico-Americano

    Guadalajara, 44620

  • Hospital General de Mexico

    Mexico City, 06726

  • Hospital Central

    San Luis Potosí City, 78240

  • Hospital CIMA Santa Engracia

    San Pedro Garza García, Nuevo León, 66260

Other trials in Mexico

Sweden3 sites

  • Universitetssjukhuset i Linkoping

    Linköping, 58185

  • Universitetssjukhuset i Lund

    Lund, 22185

  • Sodersjukhuset AB

    Stockholm, 11883

Other trials in Sweden

Estonia2 sites

  • Tartu University Hospital

    Puusepa, Tartu, 51014

  • East Tallinn Central Hospital

    Tallinn

Other trials in Estonia

United Kingdom2 sites

  • Addenbrookes Hospital

    Cambridge, Cambridgeshire, CB20QQ

  • Royal Devon and Exeter Hospital

    Exeter, Devon, EX25DW

Other trials in United Kingdom

Latvia1 site

  • P. Stradins Clinical University Hospital

    Riga, 1002

Other trials in Latvia

Netherlands1 site

  • Diabeter Center for Pediatric and Adolescent Diabetes Care and Research

    Rotterdam, 3011TG

Other trials in Netherlands

About this study

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

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.

Read the 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

Being tested
Teplizumab, Placebo
Keywords
Randomized, Double Blind, Parallel Group, Controlled Clinical Trial
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TeplizumabBiological

    Also called MGA031

    Daily IV dosing for 14 days, repeated at Week 26

  • PlaceboDrug

    Daily IV dosing for 14 days, repeated at Week 26

Study groups in NCT00385697
Study groupRoleWhat they receive
Double-blind Herold RegimenExperimentalFull dose of teplizumab IV for 14 days, repeated at Week 26
Receives: Biological: Teplizumab
Double-blind 33.3% Herold RegimenExperimentalOne third full dose of teplizumab IV for 14 days, repeated at Week 26
Receives: Biological: Teplizumab
Double-blind Curtailed Herold RegimenExperimentalFull dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26
Receives: Biological: Teplizumab
Double-blind PlaceboPlacebo comparatorPlacebo IV dosing daily for 14 days repeated at Week 26
Receives: Drug: Placebo
Open-label Herold RegimenExperimentalFull dose of teplizumab IV for 14 days, repeated at Week 26
Receives: Biological: Teplizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 52 weeks after randomization

  2. 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%

    Measured: 52 weeks after first dose

  3. 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

    Measured: 52 weeks after randomization

  4. Mean HbA1c Change From Baseline in Segment 1

    The average change in HbA1c levels after dosing.

    Measured: 52 weeks after first dose

Secondary outcomes (8)

  1. 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

    Measured: 104 weeks after randomization

  2. Change From Baseline in C-peptide AUC in Segment 1

    AUC of C-peptide secretory responses following a mixed meal eaten by the subject

    Measured: 104 weeks after first dose

  3. 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%.

    Measured: 104 weeks after randomization

  4. 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%.

    Measured: 104 weeks after first dose

  5. 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%.

    Measured: at 52 weeks after randomization

  6. 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%.

    Measured: 52 weeks after first dose

  7. Mean HbA1c Change From Baseline in Segment 2

    Comparison among study treatments of the average change from baseline in HbA1c.

    Measured: at 104 weeks after randomization

  8. Mean HbA1c Change From Baseline in Segment 1

    Comparison among study treatments of the average change from baseline in HbA1c.

    Measured: 104 weeks after first dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Oct 2006 (estimated)
  2. Study startOct 2006
  3. Primary completionJun 2010
  4. Study completionAug 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
554 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00385697
Sponsor's protocol ID
CP-MGA031-01
Status last verified
Nov 2023
First submitted
7 Oct 2006
Last updated
5 Dec 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 39735417

  • 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.

    PubMed 21719095

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Teplizumab in people with Type 1 Diabetes Mellitus, run by MacroGenics at 115 sites in 16 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 115 sites in United States, India, Poland, Ukraine, Canada and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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%. (time frame: 52 weeks after randomization). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00385697, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2023.

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