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

NCT03875729 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: PRV-031-001
• Study Type: interventional
• Target: 328
• Locations: 9 countries
• Sites: 62

Brief 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.

Conditions

Type 1 Diabetes Mellitus

Keywords

T1D, type 1 diabetes, recent-onset T1D

Outcome Measures

Primary Outcomes (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).

  Baseline to Week 78

Secondary Outcomes (8)

• Average Daily Exogenous Insulin Use

  Week 78

• Change in Glycated Hemoglobin (HbA1c) Levels (%)

  Baseline to Week 78

• Time in Range for Glycemia Control

  Week 78

• Rate of Clinically Important Hypoglycemic Events

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

• Number of Participants With Adverse Events of Special Interest (AESIs)

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

Study Arms (2)

Teplizumab

EXPERIMENTAL

Teplizumab 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.

Biological: teplizumab

Placebo

PLACEBO COMPARATOR

Placebo 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.

Biological: Placebo

Interventions

teplizumab BIOLOGICAL

Treatment

Teplizumab

Placebo BIOLOGICAL

Control

Placebo

Eligibility Criteria

• Age: 8 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Provention Bio, Inc.: lead

Study Sites (62)

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

San Diego, California, 92123, United States

Location

UCSF Medical Center (Site 001)

San Francisco, California, 94158, United States

Location

Diablo Clinical Research, Inc. (Site 002)

Walnut Creek, California, 94598, United States

Location

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

Aurora, Colorado, 80045, United States

Location

Yale University of Medicine (Site 020)

New Haven, Connecticut, 06520, United States

Location

UF Clinical and Translation Research Building (Site 015)

Gainesville, Florida, 32610, United States

Location

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

Jacksonville, Florida, 32207, United States

Location

University of Miami Health System (Site 028)

Miami, Florida, 33136, United States

Location

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

St. Petersburg, Florida, 33701, United States

Location

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

Tampa, Florida, 33612, United States

Location

Atlanta Diabetes Associates (Site 009)

Atlanta, Georgia, 30318, United States

Location

Centricity Research (Site 006)

Columbus, Georgia, 31904, United States

Location

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

Boise, Idaho, 82712, United States

Location

Rocky Mountain Diabetes and Osteoporosis Center (Site 007)

Idaho Falls, Idaho, 83404, United States

Location

University of Chicago Medical Center (Site 017)

Chicago, Illinois, 60637, United States

Location

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

Indianapolis, Indiana, 46202, United States

Location

U. Iowa Children's Hospital (Site 023)

Iowa City, Iowa, 52242, United States

Location

Capital Diabetes & Endocrine Associates (Site 029)

Camp Springs, Maryland, 20746, United States

Location

Baystate Pediatric Endocrinology & Diabetes (Site 040)

Springfield, Massachusetts, 01199, United States

Location

U. Minnesota Health Clinical Research Unit (Site 031)

Minneapolis, Minnesota, 55454, United States

Location

Children's Mercy Hospitals & Clinics (Site 026)

Kansas City, Missouri, 64108, United States

Location

Washington University School of Medicine (Site 018)

St Louis, Missouri, 63110, United States

Location

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

Buffalo, New York, 14203, United States

Location

UNC Hospitals Children's Specialty Clinic (Site 038)

Chapel Hill, North Carolina, 27599, United States

Location

Rainbow Babies & Children's Hospital (Site 049)

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic (Site 051)

Cleveland, Ohio, 44195, United States

Location

Endocrinology Service Northwest, LLC (Site 034)

Bend, Oregon, 97702, United States

Location

Childrens Hospital of Philadelphia - Endocrinology (Site 021)

Philadelphia, Pennsylvania, 19104, United States

Location

Sanford Diabetes and Thyroiid Clinical (Site 013)

Sioux Falls, South Dakota, 57105, United States

Location

AM Diabetes & Endocrinology Center (Site 008)

Bartlett, Tennessee, 38133, United States

Location

Vanderbilt University Medical Center (Site 024)

Nashville, Tennessee, 37232, United States

Location

Children's Medical Center Dallas (Site 033)

Dallas, Texas, 75235, United States

Location

Benaroya Research Institute at Virginia Mason (Site 016)

Seattle, Washington, 98101, United States

Location

MultiCare Institute for Research & Innovation (Site 003)

Tacoma, Washington, 98405, United States

Location

UZ Brussel - Campus Jette (Site 202)

Brussels, Brussels Capital, 1090, Belgium

Location

UZ Gent (Site 206)

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

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

Namur, 5000, Belgium

Location

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

Edmonton, Alberta, T6G 2J3, Canada

Location

BC Diabetes (Site 102)

Vancouver, British Columbia, Canada

Location

Montreal Children's Hospital-McGill (Site 101)

Montreal, Quebec, Canada

Location

Fakultni nemocnice v Motole (Site 301)

Prague, 150 06, Czechia

Location

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

Nice, Alpes-Maritimes, 6200, France

Location

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

Marseille, Bouces-du-Rhone, 13005, France

Location

CHU DIJON hopital d'enfant (Site 504)

Dijon, cote-d'Or, 21079, France

Location

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

Orléans, Loiret, 45100, France

Location

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

Bron, Rhone, 69677, France

Location

Centre hospitalier de Pau (Site 501)

Pau, 64046, France

Location

Groupe Hospitalier Necker Enfants Malades (site 502)

Paris, Île-de-France Region, 75015, France

Location

Universitätsklinikum Freiburg (Site 603)

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Universitätsklinikum Heidelberg (Site 608)

Heidelberg, Baden-Wurtternberg, 69120, Germany

Location

Universitätsklinikum Augsburg (Site 606)

Augsburg, Bayem, 86156, Germany

Location

Evangelisches Klinikum Bethel Kinderklinik (Site 602)

Bielefeld, North Rhine-Westphalia, 33617, Germany

Location

Universitatsklinikum Carl Gustav Carus (Site 601)

Dresden, Sachson, -1307, Germany

Location

Kinderkrankenhaus Auf Der Bult (Site 604)

Hanover, 30173, Germany

Location

Békés Megyei Központi Kórház Pándy Kálmán Tagkórház ( Site 705)

Gyula, Hungary

Location

Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu (Site 804)

Warsaw, Masovian Voivodeship, 01-184, Poland

Location

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

Warsaw, 02-117, Poland

Location

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

Warsaw, 04-730, Poland

Location

Uniwersyteckie Centrum Kliniczne (Site 803)

Warsaw, 80-952, Poland

Location

Northwick Park Hospital - Paediatrics (site 904)

London, City of London, HA1 3UJ, United Kingdom

Location

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

Cardiff, CF14 4XN, United Kingdom

Location

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

Sheffield, s10 2TH, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 37861217 RESULT

• 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.

  PMID: 39735417 DERIVED

• 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.

  PMID: 37158990 DERIVED

Related Links

• New England Journal of Medicine publication of the study results

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

teplizumab

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

Enrollment into the study was temporarily suspended due to COronaVIrus Disease of 2019 (COVID-19) pandemic restrictions. Participants who were unable to receive the second 12-day treatment course at 6 months due to COVID-19 pandemic restrictions were given the second course at approximately 12 months (modified dosing schedule).

Results Point of Contact

• Title: Clinical and Translational Medicine Lead
• Organization: Sanofi

laura.knecht@sanofi.com

1-703-344-2992

Study Officials

• Chief Medical Officer, MD

  Provention Bio, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 3, randomized, double-blind, placebo-controlled, multinational, multicenter study

Study Record Dates

• First Submitted: March 13, 2019
• First Posted: March 15, 2019
• Study Start: April 5, 2019
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2023
• Last Updated: April 24, 2024
• Results First Posted: April 24, 2024

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After drug approval
• Access Criteria: Qualified researchers

Locations

CZ (1); FR (7); PL (4); CA (3); BE (3); GB (3); US (34); DE (6); HU (1)