Long-Term Safety Evaluation of Cendakimab in Adult and Adolescent Patients with Eosinophilic Esophagitis: A Phase 3 Multicenter Open-Label Extension Study

The primary objective of this study is to evaluate the **long-term safety** and tolerability of **Cendakimab** (CC-93538) in adult and adolescent subjects diagnosed with **eosinophilic esophagitis**. This is clinically relevant as it aims to ensure that prolonged use of the medication does not result in adverse effects, thereby supporting its potential as a sustainable treatment option for this chronic condition.

Secondary objectives include characterizing the **immunogenicity** profile of CC-93538 following long-term treatment. Understanding the immunogenicity is crucial as it assesses the potential for the body to mount an immune response against the therapeutic agent, which could impact its efficacy and safety over extended use.

The clinical trial involves a total of **205 participants** diagnosed with **eosinophilic esophagitis**. The study population includes both male and female subjects, with an age range encompassing children, adolescents, and adults. Participants were selected based on their prior involvement in related studies, specifically Study CC-93538-EE-001 or Study CC-93538-DDI-001, and their compliance with investigational product dosing. The trial includes individuals who have not experienced any clinically significant adverse events related to the investigational product that would preclude further dosing. The study population is characterized by a diverse age range and includes a vulnerable population. Participants are required to have demonstrated compliance with previous study protocols and must not have been permanently discontinued from the investigational product in prior studies. Females of childbearing potential are required to have a negative pregnancy test and agree to use a highly effective method of contraception. The trial does not enroll adolescent subjects in Austria, Germany, Spain, and Switzerland. The study aims to evaluate the long-term safety and tolerability of CC-93538 in this specific patient population.

The clinical trial is designed as a **Phase 3**, multicenter, multinational, open-label extension study aimed at evaluating the long-term safety and tolerability of **Cendakimab** in adult and adolescent subjects with **eosinophilic esophagitis**. The trial will involve participants who have previously been part of Study CC-93538-EE-001 or Study CC-93538-DDI-001. The study is expected to run from September 14, 2021, to August 1, 2026, with the investigational product administered as a **solution for injection** via subcutaneous use. The trial will not include a control group, and blinding is not applicable due to its open-label nature.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on prior study participation and compliance with investigational product dosing. The primary endpoint is the safety and tolerability of long-term treatment with Cendakimab, assessed through the incidence and severity of adverse events, serious adverse events, and clinical laboratory abnormalities. Secondary endpoints include the immunogenicity of Cendakimab, evaluated by the incidence of anti-drug antibodies.

The expected length of participant involvement is up to 60 months, with conditions for early termination including the occurrence of clinically significant adverse events related to the investigational product or non-compliance with study procedures. Follow-up visits will be conducted periodically to monitor safety and collect data on adverse events and laboratory results. The end-of-study visit will conclude the participant's involvement, ensuring all safety assessments are completed. Participants must adhere to contraception requirements if applicable, and informed consent is required for all subjects, with additional assent and parental consent for those under 18 years of age.

The clinical trial involves the administration of **Cendakimab**, a recombinant medicinal product developed by Celgene Corporation. Cendakimab is provided in the form of a **solution for injection** and is intended for **subcutaneous use**. The active substance in Cendakimab is a protein of other origin, specifically designed for the treatment of eosinophilic esophagitis. The pharmaceutical form is a solution, ensuring ease of administration and absorption. The maximum daily dose of Cendakimab is 999 mg, with a total maximum dose of 93,857 mg over the course of the treatment period, which spans up to 60 days. The dosing schedule and administration frequency are determined by the study protocol, ensuring optimal therapeutic outcomes while monitoring for safety and tolerability.

In this study, Cendakimab is the primary investigational product, and no additional non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified. Participant compliance with the dosing regimen is monitored throughout the trial to ensure adherence to the protocol and to evaluate the long-term safety and tolerability of the treatment in both adult and adolescent subjects with eosinophilic esophagitis. The study is designed as an open-label extension, allowing for the collection of comprehensive safety data over an extended period.

The efficacy of the investigational product, **Cendakimab**, in the clinical trial will be assessed primarily through the evaluation of safety and tolerability. This will be determined by monitoring the incidence, severity, and relationship of adverse events (AEs) and serious adverse events (SAEs) to **Cendakimab**. Additionally, clinical laboratory abnormalities, changes in vital signs, and physical examination abnormalities will be recorded and analyzed. These parameters will provide a comprehensive overview of the long-term safety profile of **Cendakimab** in subjects with eosinophilic esophagitis.

Secondary efficacy assessments will focus on the immunogenicity of **Cendakimab**. This will involve measuring the incidence of anti-drug antibodies, including neutralizing antibodies when necessary. The collection and analysis of these data points will be conducted at specified intervals throughout the trial to ensure a thorough evaluation of the investigational product's efficacy and safety profile over the long term.