Evaluation of Mepolizumab and In-Office Nasal Polypectomy in Chronic Rhinosinusitis: A Three-Arm Randomized Controlled Trial

The primary objective of this study is to evaluate the improvement in **quality of life** for patients with chronic rhinosinusitis (CRS), as determined by the sinonasal outcome test (SNOT-22) result. This is clinically relevant as it directly assesses the impact of treatment on the patient's daily functioning and well-being, providing a comprehensive measure of treatment efficacy.

Secondary objectives include:

• Change in nasal polyposis severity VAS score at V1, V6, V12.
• Change in endoscopic nasal polyp score at V1, V6, V12.
• Improvement in individual VAS symptoms (rhinorrhea, mucus in throat, nasal blockage, and sense of smell), patient-reported outcomes at V1, V6, V12.
• Number of patients no longer requiring rescue systemic corticosteroid treatment throughout the first year after the first month of starting the study.
• Safety of **Mepolizumab** and in-office nasal polypectomy.
• Change from baseline in sinonasal outcome test (SNOT-22) total score at weeks 4 and 24.

The clinical trial focuses on participants diagnosed with **chronic rhinosinusitis (CRS)** with nasal polyps, as defined by the EPOS2020 guideline. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a diagnosis of CRS with polyposis, characterized by symptoms such as nasal blockage, discharge, facial pain, or loss of smell persisting for 12 weeks or more, along with endoscopic or CT evidence of nasal polyps. The trial does not involve a vulnerable population. Participants must have an indication for biologic treatment and meet specific criteria, including evidence of type 2 inflammation, a need for systemic corticosteroids, impaired quality of life, significant loss of smell, or a comorbid asthma diagnosis. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet and physical activity are not specified in the trial data. Participants have been informed and have signed consent to participate in the study.

The clinical trial is designed to evaluate the efficacy of **mepolizumab** in conjunction with in-office nasal polypectomy for patients diagnosed with **chronic rhinosinusitis** (CRS) with nasal polyps. This is a randomized, double-blind, controlled study with three arms, aiming to assess the primary endpoint of improvement in quality of life as measured by the Sinonasal Outcome Test (SNOT-22). The trial is categorized as a low-intervention Phase IV study, adapted to clinical practice and aligned with the authorized indication of the drug. The trial is expected to commence recruitment on September 1, 2023, and conclude by December 31, 2025.

Participants will be involved in the study for a maximum treatment period of 12 months, during which they will receive **mepolizumab** via subcutaneous injection. The study includes several key visits: an initial screening visit to confirm eligibility based on criteria such as age, diagnosis, and eosinophil count; regular follow-up visits to monitor treatment efficacy and safety; and an end-of-study visit to assess final outcomes. The inclusion criteria require participants to be 18 years or older, with a confirmed diagnosis of CRS with nasal polyps, and an indication for biologic treatment as per EPOS2020 guidelines. Exclusion criteria are not specified in the provided data.

Participants may be withdrawn from the study if they experience adverse events that compromise safety, fail to adhere to the study protocol, or withdraw consent. Secondary endpoints include the assessment of nasal symptoms using the VAS score, evaluation of nasal polyps via the Lund-Kennedy and Meltzer scales, and the need for rescue therapy or surgery. The safety of the treatment will be continuously monitored through the collection of adverse events at each study visit. The trial's design ensures rigorous assessment of both efficacy and safety, contributing valuable data to the management of CRS with nasal polyps.

The clinical trial involves the administration of **Nucala**, a pharmaceutical product containing the active substance **mepolizumab**. Mepolizumab is a monoclonal antibody classified under the ATC code R03DX09. The medication is provided as a **solution for injection** in a pre-filled syringe, specifically designed for subcutaneous administration. Each syringe contains 100 mg of mepolizumab. The maximum daily dose is 100 mg, with a total maximum dose of 1200 mg over the course of the treatment period. The treatment duration is set for a maximum of 12 months. The administration of the drug is conducted under the supervision of healthcare professionals to ensure proper dosing and participant compliance.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the effects of mepolizumab in the context of the trial's objectives. Participant compliance is monitored through regular follow-ups and assessments to ensure adherence to the dosing schedule and to evaluate the treatment's efficacy and safety. The trial aims to assess the improvement in quality of life for patients with chronic rhinosinusitis, as determined by the sinonasal outcome test (SNOT-22) results.

Efficacy in the clinical trial will be assessed primarily through the improvement in quality of life, as determined by the **Sinonasal Outcome Test (SNOT-22)**. This test serves as the primary endpoint for evaluating the effectiveness of the treatment in patients with chronic rhinosinusitis with nasal polyps. Secondary endpoints include the Visual Analog Scale (VAS) score for nasal symptoms and assessments using a nasopharyngoscope, specifically the Lund-Kennedy and Meltzer scales for chronic rhinosinusitis with nasal polyps (CRSwNP). Additionally, the need for rescue therapy with systemic corticosteroids, including dose, route of administration, length of treatment, and number of treatments, will be evaluated. The requirement for rescue surgery, either in-office polypectomy or full endoscopic sinus surgery, will also be monitored. Histological analysis of resected polyps in the polypectomy groups will confirm eosinophilic pathology and type 2 inflammation. The safety of the treatment will be assessed by collecting adverse events at each study visit. These efficacy parameters will be measured and collected at specified timepoints throughout the trial, ensuring a comprehensive evaluation of the treatment's impact on the participants.