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

NCT ID: NCT03875729

Last Updated: 2024-04-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 328 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-05
• Study Completion Date: 2023-05-01

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.

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

Conditions

Type 1 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Teplizumab

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.

Group Type: EXPERIMENTAL

teplizumab

Intervention Type: BIOLOGICAL

Treatment

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Control

Interventions

teplizumab

Treatment

Intervention Type: BIOLOGICAL

Placebo

Control

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Is 8 to 17 years of age, inclusive, at the time of randomization/initiation of study drug administration.

2. Has received a diagnosis of type 1 diabetes (T1D) according to the criteria from the American Diabetes Association.

3. Is able to be randomized and initiate study drug within 6 weeks (42 days) of the formal T1D diagnosis.

4. Has a peak stimulated C-peptide of ≥0.2 pmol/mL from a mixed meal tolerance test (MMTT) at screening.

5. Has a positive result on testing for T1D-related autoantibodies.

Exclusion Criteria

1. Has any autoimmune disease other than T1D with the exception of stable thyroid or celiac disease.

2. Has an active infection and/or fever.

3. 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).

4. 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.

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Provention Bio, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chief Medical Officer, MD

Role: STUDY_DIRECTOR

Provention Bio, Inc.

Locations

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

San Diego, California, United States

UCSF Medical Center (Site 001)

San Francisco, California, United States

Diablo Clinical Research, Inc. (Site 002)

Walnut Creek, California, United States

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

Aurora, Colorado, United States

Yale University of Medicine (Site 020)

New Haven, Connecticut, United States

UF Clinical and Translation Research Building (Site 015)

Gainesville, Florida, United States

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

Jacksonville, Florida, United States

University of Miami Health System (Site 028)

Miami, Florida, United States

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

St. Petersburg, Florida, United States

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

Tampa, Florida, United States

Atlanta Diabetes Associates (Site 009)

Atlanta, Georgia, United States

Centricity Research (Site 006)

Columbus, Georgia, United States

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

Boise, Idaho, United States

Rocky Mountain Diabetes and Osteoporosis Center (Site 007)

Idaho Falls, Idaho, United States

University of Chicago Medical Center (Site 017)

Chicago, Illinois, United States

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

Indianapolis, Indiana, United States

U. Iowa Children's Hospital (Site 023)

Iowa City, Iowa, United States

Capital Diabetes & Endocrine Associates (Site 029)

Camp Springs, Maryland, United States

Baystate Pediatric Endocrinology & Diabetes (Site 040)

Springfield, Massachusetts, United States

U. Minnesota Health Clinical Research Unit (Site 031)

Minneapolis, Minnesota, United States

Children's Mercy Hospitals & Clinics (Site 026)

Kansas City, Missouri, United States

Washington University School of Medicine (Site 018)

St Louis, Missouri, United States

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

Buffalo, New York, United States

UNC Hospitals Children's Specialty Clinic (Site 038)

Chapel Hill, North Carolina, United States

Rainbow Babies & Children's Hospital (Site 049)

Cleveland, Ohio, United States

Cleveland Clinic (Site 051)

Cleveland, Ohio, United States

Endocrinology Service Northwest, LLC (Site 034)

Bend, Oregon, United States

Childrens Hospital of Philadelphia - Endocrinology (Site 021)

Philadelphia, Pennsylvania, United States

Sanford Diabetes and Thyroiid Clinical (Site 013)

Sioux Falls, South Dakota, United States

AM Diabetes & Endocrinology Center (Site 008)

Bartlett, Tennessee, United States

Vanderbilt University Medical Center (Site 024)

Nashville, Tennessee, United States

Children's Medical Center Dallas (Site 033)

Dallas, Texas, United States

Benaroya Research Institute at Virginia Mason (Site 016)

Seattle, Washington, United States

MultiCare Institute for Research & Innovation (Site 003)

Tacoma, Washington, United States

UZ Brussel - Campus Jette (Site 202)

Brussels, Brussels Capital, Belgium

UZ Gent (Site 206)

Ghent, Oost-Vlaanderen, Belgium

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

Namur, , Belgium

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

Edmonton, Alberta, Canada

BC Diabetes (Site 102)

Vancouver, British Columbia, Canada

Montreal Children's Hospital-McGill (Site 101)

Montreal, Quebec, Canada

Fakultni nemocnice v Motole (Site 301)

Prague, , Czechia

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

Nice, Alpes-Maritimes, France

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

Marseille, Bouces-du-Rhone, France

CHU DIJON hopital d'enfant (Site 504)

Dijon, cote-d'Or, France

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

Orléans, Loiret, France

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

Bron, Rhone, France

Centre hospitalier de Pau (Site 501)

Pau, , France

Groupe Hospitalier Necker Enfants Malades (site 502)

Paris, Île-de-France Region, France

Universitätsklinikum Freiburg (Site 603)

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Universitätsklinikum Heidelberg (Site 608)

Heidelberg, Baden-Wurtternberg, Germany

Universitätsklinikum Augsburg (Site 606)

Augsburg, Bayem, Germany

Evangelisches Klinikum Bethel Kinderklinik (Site 602)

Bielefeld, North Rhine-Westphalia, Germany

Universitatsklinikum Carl Gustav Carus (Site 601)

Dresden, Sachson, Germany

Kinderkrankenhaus Auf Der Bult (Site 604)

Hanover, , Germany

Békés Megyei Központi Kórház Pándy Kálmán Tagkórház ( Site 705)

Gyula, , Hungary

Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu (Site 804)

Warsaw, Masovian Voivodeship, Poland

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

Warsaw, , Poland

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

Warsaw, , Poland

Uniwersyteckie Centrum Kliniczne (Site 803)

Warsaw, , Poland

Northwick Park Hospital - Paediatrics (site 904)

London, City of London, United Kingdom

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

Cardiff, , United Kingdom

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

Sheffield, , United Kingdom

Countries

United States; Belgium; Canada; Czechia; France; Germany; Hungary; Poland; United Kingdom

References

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.

Reference Type: RESULT

PMID: 37861217 (View on PubMed)

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)

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.

Reference Type: DERIVED

PMID: 37158990 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Study Documents

Document Type: Individual Participant Data Set

Qualified researchers can submit a research proposal that includes specific information about the purpose of the research, the objectives, the analysis plan, the publication plan, etc. Qualified researchers may request access to patient level data and related study documents. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of trial participants.

View Document

Related Links

http://pubmed.ncbi.nlm.nih.gov/37861217/

New England Journal of Medicine publication of the study results

Other Identifiers

PRV-031-001

Identifier Type: -

Identifier Source: org_study_id