Clinical trial NCT03875729: Recent-Onset Type 1 Diabetes Trial Evaluating Efficacy and Safety of Teplizumab
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 1 Diabetes Mellitus
Keywords: T1D, type 1 diabetes, recent-onset T1D
Lead sponsor: Provention Bio, Inc.
Sponsor class: INDUSTRY
First posted: 2019-03-15
Enrollment: 328
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 3, randomized, double-blind, placebo-controlled, multinational, multicenter study
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Change in C-peptide ln(AUC+1) Standardized by Duration of the Mixed Meal Tolerance Test (MMTT)
timeFrame: Baseline to Week 78
Secondary outcomes:
measure: Average Daily Exogenous Insulin Use
timeFrame: Week 78
measure: Change in Glycated Hemoglobin (HbA1c) Levels (%)
timeFrame: Baseline to Week 78
measure: Time in Range for Glycemia Control
timeFrame: Week 78
measure: Rate of Clinically Important Hypoglycemic Events
timeFrame: During the entire study (from the first dose to the last study contact, up to 78 Weeks)
measure: Number of Participants With Adverse Events of Special Interest (AESIs)
timeFrame: During the entire study (from the first dose to the last study contact, up to 78 Weeks)
measure: Teplizumab Serum Concentrations
timeFrame: 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.
measure: Anti-teplizumab Antibody (ADA) Titers After Treatment Courses
timeFrame: Baseline through 78 Week
measure: Incidence of Anti-drug Antibodies (ADA) After Treatment Courses
timeFrame: From baseline through Week 78
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Rady Children's Hospital-San Diego (Site 004)
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center (Site 001)
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research, Inc. (Site 002)
state: California
city: Aurora
country: United States
facility: University of Colorado-Barbara Davis Center for Childhood Diabetes (Site 005)
state: Colorado
city: New Haven
country: United States
facility: Yale University of Medicine (Site 020)
state: Connecticut
city: Gainesville
country: United States
facility: UF Clinical and Translation Research Building (Site 015)
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Specialty Care-Endocrinology (Site 047)
state: Florida
city: Miami
country: United States
facility: University of Miami Health System (Site 028)
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital-Johns Hopkins Medicine (Site 048)
state: Florida
city: Tampa
country: United States
facility: University of South Florida Diabetes and Endocrinology Center (Site 011)
state: Florida
city: Atlanta
country: United States
facility: Atlanta Diabetes Associates (Site 009)
state: Georgia
city: Columbus
country: United States
facility: Centricity Research (Site 006)
state: Georgia
city: Boise
country: United States
facility: St. Luke's Children's Endocrinology (Site 052)
state: Idaho
city: Idaho Falls
country: United States
facility: Rocky Mountain Diabetes and Osteoporosis Center (Site 007)
state: Idaho
city: Chicago
country: United States
facility: University of Chicago Medical Center (Site 017)
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Hospital and Riley Hospital for Children (Site 014)
state: Indiana
city: Iowa City
country: United States
facility: U. Iowa Children's Hospital (Site 023)
state: Iowa
city: Camp Springs
country: United States
facility: Capital Diabetes & Endocrine Associates (Site 029)
state: Maryland
city: Springfield
country: United States
facility: Baystate Pediatric Endocrinology & Diabetes (Site 040)
state: Massachusetts
city: Minneapolis
country: United States
facility: U. Minnesota Health Clinical Research Unit (Site 031)
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospitals & Clinics (Site 026)
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine (Site 018)
state: Missouri
city: Buffalo
country: United States
facility: Women and Children's Hospital of Buffalo (Site 010)
state: New York
city: Chapel Hill
country: United States
facility: UNC Hospitals Children's Specialty Clinic (Site 038)
state: North Carolina
city: Cleveland
country: United States
facility: Rainbow Babies & Children's Hospital (Site 049)
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic (Site 051)
state: Ohio
city: Bend
country: United States
facility: Endocrinology Service Northwest, LLC (Site 034)
state: Oregon
city: Philadelphia
country: United States
facility: Childrens Hospital of Philadelphia - Endocrinology (Site 021)
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Diabetes and Thyroiid Clinical (Site 013)
state: South Dakota
city: Bartlett
country: United States
facility: AM Diabetes & Endocrinology Center (Site 008)
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center (Site 024)
state: Tennessee
city: Dallas
country: United States
facility: Children's Medical Center Dallas (Site 033)
state: Texas
city: Seattle
country: United States
facility: Benaroya Research Institute at Virginia Mason (Site 016)
state: Washington
city: Tacoma
country: United States
facility: MultiCare Institute for Research & Innovation (Site 003)
state: Washington
city: Bruxelles
country: Belgium
facility: UZ Brussel - Campus Jette (Site 202)
state: Brussels Capital Region
city: Gent
country: Belgium
facility: UZ Gent (Site 206)
state: Oost-Vlaanderen
city: Namur
country: Belgium
facility: CHU UCL Namur, site Clinique Sainte-Elisabeth (Site 205)
city: Edmonton
country: Canada
facility: Alberta Diabetes Institute Clinical Research Unit Li Ka Shing Centre for Health Research Innovation (Site 103)
state: Alberta
city: Vancouver
country: Canada
facility: BC Diabetes (Site 102)
state: British Columbia
city: Montreal
country: Canada
facility: Montreal Children's Hospital-McGill (Site 101)
state: Quebec
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole (Site 301)
city: Nice
country: France
facility: Hopitaux Pediatriques de Nice CHU-Lenval service de diabetologie et d'endocrinologia (Site 508)
state: Alpes-Maritimes
city: Marseille
country: France
facility: CHU Hopital de la Timone-Hopital d'Enfants (Site 512)
state: Bouces-du-Rhone
city: Dijon Cedex
country: France
facility: CHU DIJON hopital d'enfant (Site 504)
state: cote-d'Or
city: Paris
country: France
facility: Groupe Hospitalier Necker Enfants Malades (site 502)
state: Ile-de-France
city: Orleans
country: France
facility: Centre Hospitalier Regional (CHR) d'Orleans-Service de pediatrie (Site 513)
state: Loiret
city: Bron Cedex
country: France
facility: Groupe hospitalier Est-Hopital Femme, Mere, Enfant (Site 509)
state: Rhone
city: Pau cedex
country: France
facility: Centre hospitalier de Pau (Site 501)
city: Freiburg im Breisgau
country: Germany
facility: Universitätsklinikum Freiburg (Site 603)
state: Baden-Wurttemberg
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg (Site 608)
state: Baden-Wurtternberg
city: Augsburg
country: Germany
facility: Universitätsklinikum Augsburg (Site 606)
state: Bayem
city: Bielefeld
country: Germany
facility: Evangelisches Klinikum Bethel Kinderklinik (Site 602)
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus (Site 601)
state: Sachson
city: Hannover
country: Germany
facility: Kinderkrankenhaus Auf Der Bult (Site 604)
city: Gyula
country: Hungary
facility: Békés Megyei Központi Kórház Pándy Kálmán Tagkórház ( Site 705)
city: Warszawa
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu (Site 804)
state: Mazowieckie
city: Warszawa
country: Poland
facility: Instytut Diabetologii Sp. z o.o. (Site 802)
city: Warszawa
country: Poland
facility: Instytut "Pomnik - Centrum Zdrowia Dziecka" (Site 801)
city: Warszawa
country: Poland
facility: Uniwersyteckie Centrum Kliniczne (Site 803)
city: London
country: United Kingdom
facility: Northwick Park Hospital - Paediatrics (site 904)
state: City Of London
city: Cardiff
country: United Kingdom
facility: Cardiff and Vale NHS Trust - University Hospital of Wales (Site 902)
city: Sheffield
country: United Kingdom
facility: Sheffield Children's NHS Foundation Trust Western Bank (Site 903)
Study officials:
affiliation: Provention Bio, Inc.
name: Chief Medical Officer, MD
role: STUDY_DIRECTOR
References:
citation: 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.