Efficacy and Safety of Depemokimab vs. Mepolizumab in Adults with Relapsing/Refractory Eosinophilic Granulomatosis with Polyangiitis (EGPA)

The primary objective of this study is to evaluate the **efficacy** of depemokimab administered subcutaneously every 26 weeks compared with mepolizumab administered subcutaneously every 4 weeks in participants with relapsing or refractory **Eosinophilic Granulomatosis with Polyangiitis (EGPA)** who are receiving standard of care (SoC) therapy. This evaluation is clinically relevant as it aims to determine the potential of depemokimab as a less frequent treatment option, which could improve patient compliance and quality of life by reducing the frequency of administration.

Secondary objectives include evaluating the efficacy of depemokimab compared with mepolizumab on additional efficacy assessments in the same patient population. These assessments will provide further insights into the comparative benefits of the two treatments, potentially influencing future therapeutic strategies for managing relapsing or refractory EGPA.

The clinical trial involves a total of **80 participants** diagnosed with **Relapsing or Refractory Eosinophilic Granulomatosis with Polyangiitis (EGPA)**, all of whom are receiving standard of care therapy. The study population includes both male and female subjects aged 18 years and older, with a weight of at least 40 kg. Participants were selected based on their documented diagnosis of EGPA for a minimum of six months, with specific clinical features such as asthma and eosinophilia. The trial includes individuals with a history of relapsing or refractory disease, as defined by specific criteria related to corticosteroid and immunosuppressive therapy. Participants are required to be on a stable dose of oral prednisolone or prednisone for at least four weeks prior to the baseline visit. The trial population is characterized by a vulnerable group, and lifestyle factors such as diet and physical activity are not specified. The inclusion of both genders and the requirement for stable medication regimens are significant aspects of the study's design.

The clinical trial is designed as a **randomized**, **double-blind**, double-dummy, parallel-group, multi-centre, non-inferiority study. It aims to evaluate the efficacy and safety of **depemokimab** compared with **mepolizumab** in adults with relapsing or refractory **Eosinophilic Granulomatosis with Polyangiitis (EGPA)** receiving standard of care therapy. The trial is set to last for 52 weeks, with the estimated recruitment start date being July 14, 2022, and the estimated end date being November 7, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, weight, and documented diagnosis of EGPA. The trial includes regular follow-up visits to monitor the participants' health status, adherence to the treatment regimen, and any adverse events. The primary endpoint is remission at both Week 36 and Week 52, defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 and a dose of oral corticosteroids (OCS) ≤4 mg/day. Secondary endpoints include the total accrued duration of remission and time to first EGPA relapse.

Participants are expected to be involved in the trial for the entire 52-week duration unless conditions arise that necessitate early termination, such as significant adverse events or non-compliance with the study protocol. The trial involves the administration of depemokimab subcutaneously every 26 weeks and mepolizumab subcutaneously every 4 weeks, with placebo controls for both treatments. The study is conducted under strict adherence to ethical guidelines, ensuring that all participants provide informed consent and meet the inclusion criteria, such as being on a stable dose of oral prednisolone or prednisone for at least four weeks prior to the baseline visit.

The clinical trial involves the administration of **Depemokimab**, a solution for injection, as the experimental medication. Depemokimab is a humanized immunoglobulin G1-kappa monoclonal antibody targeting interleukin 5. It is provided in a pre-filled syringe designed for subcutaneous use. The dosing schedule for Depemokimab is every 26 weeks, with a maximum treatment period of 48 weeks. The administration is facilitated by a single-use, disposable safety syringe, ensuring precise delivery of the drug product. Participant compliance is monitored through scheduled visits and assessments.

**Mepolizumab** serves as the comparator treatment in this study. It is also a solution for injection, administered subcutaneously. Mepolizumab is a monoclonal antibody targeting interleukin 5, similar to Depemokimab. The dosing frequency for Mepolizumab is every 4 weeks, with a maximum treatment period of 48 weeks. The drug is provided in a pre-filled syringe, repackaged and relabeled specifically for clinical trial use. The administration is conducted using a single-use, disposable safety syringe, and participant adherence is tracked through regular follow-up visits.

The study includes two placebo groups: one for Depemokimab and one for Mepolizumab. The placebo for Depemokimab is administered in a manner identical to the active drug, using a pre-filled syringe for subcutaneous injection every 26 weeks. Similarly, the placebo for Mepolizumab is administered subcutaneously every 4 weeks, also using a pre-filled syringe. These placebo treatments are designed to maintain the double-blind nature of the trial, ensuring unbiased assessment of the efficacy and safety of the active treatments.

All participants in the trial receive standard-of-care therapy for relapsing or refractory **Eosinophilic Granulomatosis with Polyangiitis (EGPA)**, in addition to the investigational treatments or placebos. The trial is structured as a 52-week, randomized, double-blind, double-dummy, parallel-group, multi-centre, non-inferiority study, aiming to evaluate the efficacy and safety of Depemokimab compared to Mepolizumab in the specified patient population.

The efficacy of the investigational drug **depemokimab** will be assessed in a 52-week, randomized, double-blind, double-dummy, parallel-group, multi-centre, non-inferiority study. The primary endpoint for evaluating efficacy is the achievement of remission, defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 and a dose of oral corticosteroids (OCS) ≤4 mg/day, at both Week 36 and Week 52. Secondary endpoints include the total accrued duration of remission over the 52-week intervention period, time to first relapse of Eosinophilic Granulomatosis with Polyangiitis (EGPA), and mean OCS dose during the last 4 weeks of the study treatment period (Weeks 49 to 52). Remission will also be assessed using the European League Against Rheumatism (EULAR) definition, which considers BVAS=0 and OCS ≤7.5 mg/day at both Week 36 and Week 52.

Data collection will occur at specified timepoints throughout the study, with efficacy parameters being measured using validated scales and laboratory tests. The accrued number of weeks in remission will be categorized into intervals of zero weeks, >0 to <12 weeks, 12 to <24 weeks, 24 to <36 weeks, or ≥36 weeks. The study will compare the efficacy of depemokimab administered subcutaneously every 26 weeks with mepolizumab administered subcutaneously every 4 weeks, in participants receiving standard of care therapy. The analysis will focus on the ability of depemokimab to maintain remission and reduce the need for corticosteroids, thereby providing a comprehensive evaluation of its efficacy in managing relapsing or refractory EGPA.