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Type 1 Diabetes MellitusPhase 3PROTECTNCT03875729

Recent-Onset Type 1 Diabetes Trial Evaluating Efficacy and Safety of Teplizumab

A Phase 3 study testing teplizumab in people with Type 1 Diabetes Mellitus, run by Provention Bio, Inc. at 62 sites in 9 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 purpose of this study is to determine whether teplizumab slows the loss of β cells and preserves β cell function in children and adolescent 8-17 years old who have been diagnosed with T1D in the previous 6 weeks.. Subjects will receive two courses of either teplizumab or placebo treatment 6 months apart. Read more about this study

Who is it for?
Ages 8 to 17 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
328 participants
Where
62 sitesin 9 countries
Study dates
5 Apr 2019to 1 May 2023
Phase
Phase 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 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Is 8 to 17 years of age, inclusive, at the time of randomization/initiation of study drug administration.
  • Has received a diagnosis of type 1 diabetes (T1D) according to the criteria from the American Diabetes Association.
  • Is able to be randomized and initiate study drug within 6 weeks (42 days) of the formal T1D diagnosis.
  • Has a peak stimulated C-peptide of ≥0.2 pmol/mL from a mixed meal tolerance test (MMTT) at screening.
  • Has a positive result on testing for T1D-related autoantibodies.

Who cannot join

  • Has any autoimmune disease other than T1D with the exception of stable thyroid or celiac disease.
  • Has an active infection and/or fever.
  • Has a history of or serologic evidence at screening of current or past infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
  • An individual who has a medical, psychological or social condition that, in the opinion of the Principal Investigator, would interfere with safe and proper completion of the trial.

Trial locations and contacts

62 sites in 9 countries.

62 sites in 9 countries

United States34 sites

  • Atlanta Diabetes Associates (Site 009)

    Atlanta, Georgia, 30318

  • University of Colorado-Barbara Davis Center for Childhood Diabetes (Site 005)

    Aurora, Colorado, 80045

  • AM Diabetes & Endocrinology Center (Site 008)

    Bartlett, Tennessee, 38133

  • Endocrinology Service Northwest, LLC (Site 034)

    Bend, Oregon, 97702

  • St. Luke's Children's Endocrinology (Site 052)

    Boise, Idaho, 82712

  • Women and Children's Hospital of Buffalo (Site 010)

    Buffalo, New York, 14203

  • Capital Diabetes & Endocrine Associates (Site 029)

    Camp Springs, Maryland, 20746

  • UNC Hospitals Children's Specialty Clinic (Site 038)

    Chapel Hill, North Carolina, 27599

  • University of Chicago Medical Center (Site 017)

    Chicago, Illinois, 60637

  • Rainbow Babies & Children's Hospital (Site 049)

    Cleveland, Ohio, 44106

  • Cleveland Clinic (Site 051)

    Cleveland, Ohio, 44195

  • Centricity Research (Site 006)

    Columbus, Georgia, 31904

  • Children's Medical Center Dallas (Site 033)

    Dallas, Texas, 75235

  • UF Clinical and Translation Research Building (Site 015)

    Gainesville, Florida, 32610

  • Rocky Mountain Diabetes and Osteoporosis Center (Site 007)

    Idaho Falls, Idaho, 83404

  • Indiana University Hospital and Riley Hospital for Children (Site 014)

    Indianapolis, Indiana, 46202

  • U. Iowa Children's Hospital (Site 023)

    Iowa City, Iowa, 52242

  • Nemours Children's Specialty Care-Endocrinology (Site 047)

    Jacksonville, Florida, 32207

  • Children's Mercy Hospitals & Clinics (Site 026)

    Kansas City, Missouri, 64108

  • University of Miami Health System (Site 028)

    Miami, Florida, 33136

  • U. Minnesota Health Clinical Research Unit (Site 031)

    Minneapolis, Minnesota, 55454

  • Vanderbilt University Medical Center (Site 024)

    Nashville, Tennessee, 37232

  • Yale University of Medicine (Site 020)

    New Haven, Connecticut, 06520

  • Childrens Hospital of Philadelphia - Endocrinology (Site 021)

    Philadelphia, Pennsylvania, 19104

  • Rady Children's Hospital-San Diego (Site 004)

    San Diego, California, 92123

  • UCSF Medical Center (Site 001)

    San Francisco, California, 94158

  • Benaroya Research Institute at Virginia Mason (Site 016)

    Seattle, Washington, 98101

  • Sanford Diabetes and Thyroiid Clinical (Site 013)

    Sioux Falls, South Dakota, 57105

  • Baystate Pediatric Endocrinology & Diabetes (Site 040)

    Springfield, Massachusetts, 01199

  • Washington University School of Medicine (Site 018)

    St Louis, Missouri, 63110

  • All Children's Hospital-Johns Hopkins Medicine (Site 048)

    St. Petersburg, Florida, 33701

  • MultiCare Institute for Research & Innovation (Site 003)

    Tacoma, Washington, 98405

  • University of South Florida Diabetes and Endocrinology Center (Site 011)

    Tampa, Florida, 33612

  • Diablo Clinical Research, Inc. (Site 002)

    Walnut Creek, California, 94598

Other trials in United States

France7 sites

  • Groupe hospitalier Est-Hopital Femme, Mere, Enfant (Site 509)

    Bron, Rhone, 69677

  • CHU DIJON hopital d'enfant (Site 504)

    Dijon, cote-d'Or, 21079

  • CHU Hopital de la Timone-Hopital d'Enfants (Site 512)

    Marseille, Bouces-du-Rhone, 13005

  • Hopitaux Pediatriques de Nice CHU-Lenval service de diabetologie et d'endocrinologia (Site 508)

    Nice, Alpes-Maritimes, 6200

  • Centre Hospitalier Regional (CHR) d'Orleans-Service de pediatrie (Site 513)

    Orléans, Loiret, 45100

  • Groupe Hospitalier Necker Enfants Malades (site 502)

    Paris, Île-de-France Region, 75015

  • Centre hospitalier de Pau (Site 501)

    Pau, 64046

Other trials in France

Germany6 sites

  • Universitätsklinikum Augsburg (Site 606)

    Augsburg, Bayem, 86156

  • Evangelisches Klinikum Bethel Kinderklinik (Site 602)

    Bielefeld, North Rhine-Westphalia, 33617

  • Universitatsklinikum Carl Gustav Carus (Site 601)

    Dresden, Sachson, -1307

  • Universitätsklinikum Freiburg (Site 603)

    Freiburg im Breisgau, Baden-Wurttemberg, 79106

  • Kinderkrankenhaus Auf Der Bult (Site 604)

    Hanover, 30173

  • Universitätsklinikum Heidelberg (Site 608)

    Heidelberg, Baden-Wurtternberg, 69120

Other trials in Germany

Poland4 sites

  • Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu (Site 804)

    Warsaw, Masovian Voivodeship, 01-184

  • Instytut Diabetologii Sp. z o.o. (Site 802)

    Warsaw, 02-117

  • Instytut "Pomnik - Centrum Zdrowia Dziecka" (Site 801)

    Warsaw, 04-730

  • Uniwersyteckie Centrum Kliniczne (Site 803)

    Warsaw, 80-952

Other trials in Poland

Belgium3 sites

  • UZ Brussel - Campus Jette (Site 202)

    Brussels, Brussels Capital, 1090

  • UZ Gent (Site 206)

    Ghent, Oost-Vlaanderen, 9000

  • CHU UCL Namur, site Clinique Sainte-Elisabeth (Site 205)

    Namur, 5000

Other trials in Belgium

Canada3 sites

  • Alberta Diabetes Institute Clinical Research Unit Li Ka Shing Centre for Health Research Innovation (Site 103)

    Edmonton, Alberta, T6G 2J3

  • Montreal Children's Hospital-McGill (Site 101)

    Montreal, Quebec

  • BC Diabetes (Site 102)

    Vancouver, British Columbia

Other trials in Canada

United Kingdom3 sites

  • Cardiff and Vale NHS Trust - University Hospital of Wales (Site 902)

    Cardiff, CF14 4XN

  • Northwick Park Hospital - Paediatrics (site 904)

    London, City of London, HA1 3UJ

  • Sheffield Children's NHS Foundation Trust Western Bank (Site 903)

    Sheffield, s10 2TH

Other trials in United Kingdom

Czechia1 site

  • Fakultni nemocnice v Motole (Site 301)

    Prague, 150 06

Other trials in Czechia

Hungary1 site

  • Békés Megyei Központi Kórház Pándy Kálmán Tagkórház ( Site 705)

    Gyula

Other trials in Hungary

About this study

Official title: Phase 3 Randomized Double-Blind Multinational Placebo-Controlled Study to Evaluate Efficacy and Safety of Teplizumab, a Humanized Fc Receptor (FcR) Non-Binding Anti-cluster of Differentiation 3 (CD3) Monoclonal Antibody, in Children and Adolescents With Newly Diagnosed Type 1 Diabetes

The purpose of this study is to determine whether teplizumab slows the loss of β cells and preserves β cell function in children and adolescent 8-17 years old who have been diagnosed with T1D in the previous 6 weeks..

Subjects will receive two courses of either teplizumab or placebo treatment 6 months apart.

Read the detailed description

This is a Phase 3, randomized, double-blind, placebo-controlled, multinational, multi-center study to evaluate the efficacy and safety of teplizumab, a humanized, anti-CD3 monoclonal antibody, in children and adolescents ages 8 through 17 recently diagnosed with type 1 diabetes (within 6 weeks of diagnosis). Approximately 300 participants will be randomized at a ratio of 2:1 to either the teplizumab group or the placebo group.

Teplizumab or matching placebo will be administered in two courses 6 months apart. Each course of treatment will include daily infusions for 12 days. The total study duration for each participant will be up to 86 weeks.

The primary objective is to determine whether two courses of teplizumab administered 6 months apart slows the loss of β cells and preserves β cell function over 18 months (78 weeks) in children and adolescents 8-17 years old who have been diagnosed with T1D in the previous 6 weeks.

The secondary objectives are to evaluate improvements in key clinical parameters of diabetes management, to determine the safety and tolerability of teplizumab, and to evaluate the pharmacokinetics (PK) and immunogenicity of teplizumab

Being tested
teplizumab, Placebo
Keywords
T1D, type 1 diabetes, recent-onset T1D
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

    Treatment

  • PlaceboBiological

    Control

Study groups in NCT03875729
Study groupRoleWhat they receive
TeplizumabExperimentalTeplizumab was administered via intravenous infusion in two courses, with the first course starting on Day 1 (Week 1) and the second course approximately 6 months later at Day 182 (Week 26). Participants who were unable to receive the second 12-day course due to COronaVIrus Disease of 2019 (COVID-19) pandemic restrictions were given the second course at approximately 12 months (Week 52 visit). Each course of treatment included daily infusions for 12 days. Each course included: * Day 1: 106 μg/m^2 * Day 2: 425 μg/m^2 * Days 3-12: 850 μg/m^2 Total per course: 9.0 mg/m^2 The doses of study drug were calculated based on the participant's body surface area (BSA) measured on the first day of each treatment course.
Receives: Biological: teplizumab
PlaceboPlacebo comparatorPlacebo was administered via intravenous infusion in two courses, with the first course starting on Day 1 (Week 1) and the second course approximately 6 months later at Day 182 (Week 26). Participants who were unable to receive the second 12-day course due to COronaVIrus Disease of 2019 (COVID-19) pandemic restrictions were given the second course at approximately 12 months (Week 52 visit). Each course of treatment included daily infusions for 12 days. The placebo solution consisted of the same formulation as the study drug but without teplizumab. Placebo was administered in the same dose volume and by the same treatment schedule as the active drug.
Receives: Biological: Placebo

What is being measured

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

  1. Change in C-peptide ln(AUC+1) Standardized by Duration of the Mixed Meal Tolerance Test (MMTT)

    The area under the concentration-time curve (AUC) of C-peptide was measured after a 4-hour mixed meal tolerance test (MMTT) and is a measure of endogenous insulin production and β cell function. The AUC was computed using the trapezoidal rule and standardized by the duration of the MMTT test, i.e., AUC was divided by the last blood sample collection time (240 minutes or the last collection time for 4h MMTT).

    Measured: Baseline to Week 78

Secondary outcomes (8)

  1. Average Daily Exogenous Insulin Use

    The average daily insulin use was calculated based on participants who have at least 3 days of insulin use recorded in the dairy for the Week 78 visit.

    Measured: Week 78

  2. Change in Glycated Hemoglobin (HbA1c) Levels (%)

    Change in percentage (%) glycated hemoglobin (HbA1c)

    Measured: Baseline to Week 78

  3. Time in Range for Glycemia Control

    Time in range (%) for glycemia control was assessed using Continuous Glucose Monitoring (CGM). Time in range was defined as daily average percentage of time a participant's glucose is >= 70 mg/dL and <=180 mg/dL. Time in range was calculated based on participants who had at least 3 days of CGM data recorded for Week 78 visit with a range of at least 8 hours on a given day.

    Measured: Week 78

  4. Rate of Clinically Important Hypoglycemic Events

    Rate = clinically important hypoglycemic events/patient-year. A clinically important episode was defined as a blood glucose value of <54 mg/dL (3.0 mmol/L) (i.e., Level 2 Hypoglycemia, International Hypoglycemia Study Group, 2017) or a hypoglycemia event of severe cognitive impairment requiring external assistance (such as seizure, syncope, severe confusion with or without a confirmatory low blood glucose reading) (i.e., Level 3 Hypoglycemia, International Hypoglycemia Study Group 2017). Event rate was calculated for each participant as number of events / total study follow-up time. Total study follow-up time was calculated as (the date of last study contact - the first dose date + 1)/365.25. The summary is based on the data reported post-baseline in the Hypoglycemic Events Electronic Diary (eDiary).

    Measured: During the entire study (from the first dose to the last study contact, up to 78 Weeks)

  5. Number of Participants With Adverse Events of Special Interest (AESIs)

    AESIs are defined in the protocol and categories in the statistical analysis plan. Participants with multiple events are counted only once for each preferred term and category.

    Measured: During the entire study (from the first dose to the last study contact, up to 78 Weeks)

  6. Teplizumab Serum Concentrations

    PK samples were collected prior to dosing except for Day 9 in Course 1. An additional PK sample was collected 45 minutes after infusion on Day 9 in Course 1. Concentration values below Lower Limit of Quantification (2.50 ng/mL) were set to zero for summary statistics. Course 2 day numbers were set relative to the first day of dosing, regardless of normal or modified dosing schedule.

    Measured: Pre-dose samples collected on Days 1, 4, 9, 12 and 28 for each of the two treatment courses, and one post-dose sample collected on Day 9 during the first treatment course.

  7. Anti-teplizumab Antibody (ADA) Titers After Treatment Courses

    Baseline was defined as the most recent value collected prior to the first dose of study drug. Week 26 Day 187 and Weeks 27 and 34 are planned for subjects under the normal dosing schedule. Week 52 Day 369 and Weeks 53, 56, and 60 are planned for subjects under the modified dosing schedule.

    Measured: Baseline through 78 Week

  8. Incidence of Anti-drug Antibodies (ADA) After Treatment Courses

    Baseline is defined as the most recent value collected prior to the first dose of study drug. Week 26 Day 187 and Weeks 27 and 34 are planned for subjects under the normal dosing schedule. Week 52 Day 369 and Weeks 53, 56, and 60 are planned for subjects under the modified dosing schedule.

    Measured: From baseline through Week 78

Timeline

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

  1. First posted15 Mar 2019
  2. Study start5 Apr 2019
  3. Primary completion1 May 2023
  4. Study completion1 May 2023

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Phase 3, randomized, double-blind, placebo-controlled, multinational, multicenter study
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
328 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03875729
Sponsor's protocol ID
PRV-031-001
Acronym
PROTECT
Status last verified
Aug 2023
First submitted
13 Mar 2019
Last updated
24 Apr 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient levels data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org.

Publications

  • Ramos EL, Dayan CM, Chatenoud L, Sumnik Z, Simmons KM, Szypowska A, Gitelman SE, Knecht LA, Niemoeller E, Tian W, Herold KC; PROTECT Study Investigators. Teplizumab and beta-Cell Function in Newly Diagnosed Type 1 Diabetes. N Engl J Med. 2023 Dec 7;389(23):2151-2161. doi: 10.1056/NEJMoa2308743. Epub 2023 Oct 18.

    PubMed 37861217

  • Herold KC, Dayan CM, Chatenoud L, Gitelman SE, Sumnik Z, Simmons K, Szypowska A, Knecht LA, Niemoeller E, Rigby MR, Tian W, Hill R, Ramos EL. Preserving beta cell function in children and adolescents with newly diagnosed stage 3 type 1 diabetes: per-protocol population analysis from the PROTECT randomised trial. Diabetologia. 2026 Sep 10. doi: 10.1007/s00125-026-06849-5. Online ahead of print.

    PubMed 42720752

  • 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

  • Novograd J, Frishman WH. Teplizumab Therapy to Delay the Onset of Type 1 Diabetes. Cardiol Rev. 2024 Nov-Dec 01;32(6):572-576. doi: 10.1097/CRD.0000000000000563. Epub 2023 May 9.

    PubMed 37158990

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing teplizumab in people with Type 1 Diabetes Mellitus, run by Provention Bio, Inc. at 62 sites in 9 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 5 inclusion and 4 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 24 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 62 sites in United States, France, Germany, Poland, Belgium and 4 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 phase mean?

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 24 Apr 2024). 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?

Change in C-peptide ln(AUC+1) Standardized by Duration of the Mixed Meal Tolerance Test (MMTT) (time frame: Baseline to Week 78). 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 NCT03875729, which also lists 4 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 24 Apr 2024.

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