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

Phase 3

Completed

Conditions: Type 1 Diabetes Mellitus

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

Inclusion Criteria

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.

Exclusion Criteria

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

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): Rady Children's Hospital-San Diego (Site 004)
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San Diego, California, United States
UCSF Medical Center (Site 001)
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San Francisco, California, United States
Diablo Clinical Research, Inc. (Site 002)
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Walnut Creek, California, United States
University of Colorado-Barbara Davis Center for Childhood Diabetes (Site 005)
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Aurora, Colorado, United States
Yale University of Medicine (Site 020)
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New Haven, Connecticut, United States
UF Clinical and Translation Research Building (Site 015)
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Gainesville, Florida, United States
Nemours Children's Specialty Care-Endocrinology (Site 047)
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Jacksonville, Florida, United States
University of Miami Health System (Site 028)
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Miami, Florida, United States
All Children's Hospital-Johns Hopkins Medicine (Site 048)
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Saint Petersburg, Florida, United States
University of South Florida Diabetes and Endocrinology Center (Site 011)
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Tampa, Florida, United States
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Rady Children's Hospital-San Diego (Site 004)
🇺🇸San Diego, California, United States