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

Study Overview
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Brief Summary
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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
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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

Official Title
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Phase 3 Randomized Double-Blind Multinational Placebo-Controlled Study to Evaluate Efficacy and Safety of Teplizumab, a Humanized FcR Non-Binding Anti-CD3 Monoclonal Antibody, in Children and Adolescents With Newly Diagnosed Type 1 Diabetes

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Biological: teplizumab
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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 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.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase 3, randomized, double-blind, placebo-controlled, multinational, multicenter study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: teplizumab<br>Sterile solution for injection. | Biological: teplizumab<br>* Treatment<br>|
| Placebo Comparator: Placebo<br>Sterile solution for injection | Biological: Placebo<br>* Control<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The area under the time-concentration curve (AUC) of C-peptide after a mixed meal tolerance test (MMTT) at Week 78 | Clinical Endpoint | Week 78 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exogenous insulin use | Clinical Endpoint | Week 78 | 
| HbA1c levels | Clinical Endpoint | Week 78 | 
| Time in glycemic target range | Clinical Endpoint | Week 78 | 
| Clinically important hypoglycemic episodes | Clinical Endpoint | Week 78 | 
| Incidence of treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), and serious adverse events (SAEs) | Safety Endpoint | Up to Week 52 and Week 78 | 
| Teplizumab serum concentrations | PK Endpoint | 78 Week | 
| Incidence and titers of anti-teplizumab antibodies after treatment courses | Immunogenicity Endpoint | 78 Week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T1D, type 1 diabetes, recent-onset T1D