Long-Term Safety Evaluation of Teplizumab in Pediatric and Adolescent Patients with Recent-Onset Type 1 Diabetes Mellitus: An Extension of Study PRV-031-001

The primary objective of this study is to evaluate the **long-term safety** of **teplizumab**, a humanized, FcR non-binding, anti-CD3 monoclonal antibody, in children and adolescents with recent-onset **Type 1 Diabetes Mellitus**. This evaluation is conducted over an additional 42 months of follow-up for participants who previously completed the PRV-031-001 (PROTECT) study. The clinical relevance of this objective lies in ensuring the sustained safety of teplizumab, which is crucial for its potential use in managing Type 1 Diabetes Mellitus in a pediatric population.

Secondary objectives include: - Evaluating clinical parameters of diabetes management, such as insulin use and HbA1c levels, during the 42 months of follow-up. These parameters are essential for understanding the impact of teplizumab on diabetes control and management over an extended period.

The clinical trial involves a total of **122 participants** who have previously completed the PRV-031-001 (PROTECT) study. The study population includes both **male and female** subjects, with an age range that encompasses both children and adults. Participants are individuals diagnosed with **Type 1 Diabetes Mellitus**. The trial population was selected based on their completion of the Week 78 visit in the prior study, regardless of the number of doses of the study drug administered. Written informed consent was required within 12 months of the Week 78 visit, with written assent obtained for participants under 18 years of age. The study includes a vulnerable population, indicating that special considerations are in place to ensure the safety and ethical treatment of all participants. Lifestyle factors such as diet and physical activity were not specified in the available data.

The clinical trial is designed to evaluate the long-term safety of **teplizumab**, a humanized, FcR non-binding, anti-CD3 monoclonal antibody, in children and adolescents with recent-onset **Type 1 Diabetes Mellitus**. This is a Phase 3, multicenter, multinational extension study, following participants who have completed the PRV-031-001 (PROTECT) study. The trial employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. The estimated duration of the trial is approximately 42 months, with participant recruitment having commenced on August 25, 2021, and the study expected to conclude by October 12, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on the completion of the Week 78 visit in the prior study. Written informed consent is required within 12 months of this visit, with assent obtained for those under 18 years of age. The study includes regular follow-up visits to monitor the incidence of adverse events, serious adverse events, and adverse events of special interest, such as infections and malignancies. Secondary endpoints include the assessment of the area under the time-versus-concentration curve of C-peptide, insulin use, and HbA1c levels. The end-of-study visit will mark the conclusion of the participant's involvement, with data collected throughout the trial to evaluate the primary and secondary endpoints.

Participant involvement is expected to last for the entire duration of the trial, approximately 42 months, unless conditions arise that necessitate early termination. Such conditions may include the occurrence of significant adverse events or withdrawal of consent. The trial is conducted under strict adherence to ethical guidelines and regulatory requirements to ensure participant safety and the integrity of the data collected.

The clinical trial involves the administration of **Teplizumab**, a humanized, FcR non-binding, anti-CD3 monoclonal antibody, designed for the treatment of recent-onset **Type 1 Diabetes Mellitus** in children and adolescents. **Teplizumab** is provided in the pharmaceutical form of a **concentrate for solution for infusion**. The medication is administered intravenously. The dosing regimen specifies a maximum daily dose of 850 µg/m² and a maximum total dose of 18 mg/m² over a treatment period of up to 24 days. The product is classified as a biological medicinal product, and it is not formulated specifically for pediatric use. The trial aims to evaluate the long-term safety of **Teplizumab** over an additional 42 months of follow-up for participants who have completed the initial study.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint focuses on the safety profile of **Teplizumab**, specifically evaluating the incidence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs), including infections and malignancies. This will provide insight into the long-term safety of the treatment in children and adolescents with recent-onset Type 1 Diabetes Mellitus.

Secondary endpoints will include the area under the time-versus-concentration curve (AUC) of C-peptide after a 4-hour mixed-meal tolerance test (MMTT), which serves as a measure of endogenous insulin production and **β cell** function. Additionally, insulin use will be monitored, defined as a daily average dose in units per kilogram per day (U/kg/day), along with HbA1c levels. These parameters will be collected and analyzed to evaluate the efficacy of Teplizumab in maintaining or improving pancreatic function and glycemic control over the course of the study.