Recent-Onset Type 1 Diabetes Trial Evaluating Efficacy and Safety of Teplizumab
- Conditions
- Type 1 Diabetes Mellitus
- Interventions
- Biological: PlaceboBiological: teplizumab
- Registration Number
- NCT03875729
- Lead Sponsor
- Provention Bio, Inc.
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 328
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo 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. Teplizumab 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.
- Primary Outcome Measures
Name Time Method Change in C-peptide ln(AUC+1) Standardized by Duration of the Mixed Meal Tolerance Test (MMTT) Baseline to Week 78 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).
- Secondary Outcome Measures
Name Time Method 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) 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.
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses Baseline through 78 Week 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.
Change in Glycated Hemoglobin (HbA1c) Levels (%) Baseline to Week 78 Change in percentage (%) glycated hemoglobin (HbA1c)
Time in Range for Glycemia Control Week 78 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.
Teplizumab Serum Concentrations 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. 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.
Average Daily Exogenous Insulin Use Week 78 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.
Rate of Clinically Important Hypoglycemic Events During the entire study (from the first dose to the last study contact, up to 78 Weeks) 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).
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses From baseline through Week 78 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.
Trial Locations
- Locations (62)
Indiana University Hospital and Riley Hospital for Children (Site 014)
🇺🇸Indianapolis, Indiana, United States
Benaroya Research Institute at Virginia Mason (Site 016)
🇺🇸Seattle, Washington, United States
U. Minnesota Health Clinical Research Unit (Site 031)
🇺🇸Minneapolis, Minnesota, United States
Atlanta Diabetes Associates (Site 009)
🇺🇸Atlanta, Georgia, United States
Rady Children's Hospital-San Diego (Site 004)
🇺🇸San Diego, California, United States
Diablo Clinical Research, Inc. (Site 002)
🇺🇸Walnut Creek, California, United States
University of Chicago Medical Center (Site 017)
🇺🇸Chicago, Illinois, United States
Children's Mercy Hospitals & Clinics (Site 026)
🇺🇸Kansas City, Missouri, United States
Rainbow Babies & Children's Hospital (Site 049)
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic (Site 051)
🇺🇸Cleveland, Ohio, United States
CHU UCL Namur, site Clinique Sainte-Elisabeth (Site 205)
🇧🇪Namur, Belgium
Baystate Pediatric Endocrinology & Diabetes (Site 040)
🇺🇸Springfield, Massachusetts, United States
Women and Children's Hospital of Buffalo (Site 010)
🇺🇸Buffalo, New York, United States
Childrens Hospital of Philadelphia - Endocrinology (Site 021)
🇺🇸Philadelphia, Pennsylvania, United States
UNC Hospitals Children's Specialty Clinic (Site 038)
🇺🇸Chapel Hill, North Carolina, United States
MultiCare Institute for Research & Innovation (Site 003)
🇺🇸Tacoma, Washington, United States
Groupe Hospitalier Necker Enfants Malades (site 502)
🇫🇷Paris, Ile-de-France, France
CHU Hopital de la Timone-Hopital d'Enfants (Site 512)
🇫🇷Marseille, Bouces-du-Rhone, France
Universitätsklinikum Freiburg (Site 603)
🇩🇪Freiburg im Breisgau, Baden-Wurttemberg, Germany
Cardiff and Vale NHS Trust - University Hospital of Wales (Site 902)
🇬🇧Cardiff, United Kingdom
Groupe hospitalier Est-Hopital Femme, Mere, Enfant (Site 509)
🇫🇷Bron Cedex, Rhone, France
Universitätsklinikum Heidelberg (Site 608)
🇩🇪Heidelberg, Baden-Wurtternberg, Germany
Children's Medical Center Dallas (Site 033)
🇺🇸Dallas, Texas, United States
University of Colorado-Barbara Davis Center for Childhood Diabetes (Site 005)
🇺🇸Aurora, Colorado, United States
University of South Florida Diabetes and Endocrinology Center (Site 011)
🇺🇸Tampa, Florida, United States
UCSF Medical Center (Site 001)
🇺🇸San Francisco, California, United States
Centricity Research (Site 006)
🇺🇸Columbus, Georgia, United States
Rocky Mountain Diabetes and Osteoporosis Center (Site 007)
🇺🇸Idaho Falls, Idaho, United States
U. Iowa Children's Hospital (Site 023)
🇺🇸Iowa City, Iowa, United States
Washington University School of Medicine (Site 018)
🇺🇸Saint Louis, Missouri, United States
Endocrinology Service Northwest, LLC (Site 034)
🇺🇸Bend, Oregon, United States
Fakultni nemocnice v Motole (Site 301)
🇨🇿Praha 5, Czechia
Centre hospitalier de Pau (Site 501)
🇫🇷Pau cedex, France
Békés Megyei Központi Kórház Pándy Kálmán Tagkórház ( Site 705)
🇭🇺Gyula, Hungary
Sheffield Children's NHS Foundation Trust Western Bank (Site 903)
🇬🇧Sheffield, United Kingdom
St. Luke's Children's Endocrinology (Site 052)
🇺🇸Boise, Idaho, United States
All Children's Hospital-Johns Hopkins Medicine (Site 048)
🇺🇸Saint Petersburg, Florida, United States
Montreal Children's Hospital-McGill (Site 101)
🇨🇦Montreal, Quebec, Canada
Universitätsklinikum Augsburg (Site 606)
🇩🇪Augsburg, Bayem, Germany
Alberta Diabetes Institute Clinical Research Unit Li Ka Shing Centre for Health Research Innovation (Site 103)
🇨🇦Edmonton, Alberta, Canada
Capital Diabetes & Endocrine Associates (Site 029)
🇺🇸Camp Springs, Maryland, United States
UZ Brussel - Campus Jette (Site 202)
🇧🇪Bruxelles, Brussels Capital Region, Belgium
Universitatsklinikum Carl Gustav Carus (Site 601)
🇩🇪Dresden, Sachson, Germany
Instytut Diabetologii Sp. z o.o. (Site 802)
🇵🇱Warszawa, Poland
Northwick Park Hospital - Paediatrics (site 904)
🇬🇧London, City Of London, United Kingdom
Yale University of Medicine (Site 020)
🇺🇸New Haven, Connecticut, United States
UF Clinical and Translation Research Building (Site 015)
🇺🇸Gainesville, Florida, United States
BC Diabetes (Site 102)
🇨🇦Vancouver, British Columbia, Canada
Sanford Diabetes and Thyroiid Clinical (Site 013)
🇺🇸Sioux Falls, South Dakota, United States
CHU DIJON hopital d'enfant (Site 504)
🇫🇷Dijon Cedex, cote-d'Or, France
Evangelisches Klinikum Bethel Kinderklinik (Site 602)
🇩🇪Bielefeld, Nordrhein-Westfalen, Germany
AM Diabetes & Endocrinology Center (Site 008)
🇺🇸Bartlett, Tennessee, United States
University of Miami Health System (Site 028)
🇺🇸Miami, Florida, United States
Vanderbilt University Medical Center (Site 024)
🇺🇸Nashville, Tennessee, United States
UZ Gent (Site 206)
🇧🇪Gent, Oost-Vlaanderen, Belgium
Hopitaux Pediatriques de Nice CHU-Lenval service de diabetologie et d'endocrinologia (Site 508)
🇫🇷Nice, Alpes-Maritimes, France
Kinderkrankenhaus Auf Der Bult (Site 604)
🇩🇪Hannover, Germany
Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu (Site 804)
🇵🇱Warszawa, Mazowieckie, Poland
Uniwersyteckie Centrum Kliniczne (Site 803)
🇵🇱Warszawa, Poland
Nemours Children's Specialty Care-Endocrinology (Site 047)
🇺🇸Jacksonville, Florida, United States
Centre Hospitalier Regional (CHR) d'Orleans-Service de pediatrie (Site 513)
🇫🇷Orleans, Loiret, France
Instytut "Pomnik - Centrum Zdrowia Dziecka" (Site 801)
🇵🇱Warszawa, Poland