Evaluation of Biologic Tapering with Mepolizumab and Dupilumab in Patients with Severe Chronic Rhinosinusitis with Nasal Polyps: A Danish RCT

The primary objective of this study is to evaluate the impact of prolonged dosing intervals of biologic therapy in patients with **chronic rhinosinusitis with nasal polyps (CRSwNP)** who have demonstrated stable, partly controlled disease. The study specifically aims to assess the percentage of patients achieving sustained partly controlled disease after tapering biologics, Mepolizumab or Dupilumab, over a 52-week period. This is clinically relevant as it may inform treatment strategies for maintaining disease control while potentially reducing medication burden and associated costs.

Secondary objectives include:

• Assessing changes in health-related outcomes from baseline to 52 weeks.
• Comparing the two drugs to determine if one is better suited for prolonged dosing intervals.
• Identifying factors associated with continued disease control.

The clinical trial involves participants diagnosed with **chronic rhinosinusitis with nasal polyps (CRSwNP)**. The study population includes both male and female subjects aged 18 years and older. Participants are required to have been receiving treatment with either Dupilumab or Mepolizumab at a consistent dosing interval for at least three months prior to the study. The trial focuses on individuals who have maintained a partly controlled disease state for a minimum of 12 months. The selection criteria ensure that participants have a stable health status concerning their CRSwNP condition. The trial does not include vulnerable populations. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet and physical activity are not specified as part of the study's considerations.

The clinical trial is designed to evaluate the impact of prolonged dosing intervals of biologic therapy in patients with **chronic rhinosinusitis with nasal polyps (CRSwNP)** who have demonstrated stable, partly controlled disease. This is a randomized, double-blind, controlled trial with an estimated duration from March 2025 to March 2028. The trial will involve the administration of either **Dupilumab** or **Mepolizumab**, both delivered as a solution for injection in pre-filled syringes. The primary objective is to assess the percentage of patients achieving sustained partly controlled disease after tapering of biologics over a 52-week period. The trial will include a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years) and current treatment with either Dupilumab (300 mg) or Mepolizumab (100 mg) every four weeks. Participants must have received the biologic at an unchanged dosing interval for at least three months and have a history of partly controlled disease for at least one year.

Following the screening visit, participants will undergo regular follow-up visits to monitor disease control and adjust treatment as necessary. The primary endpoint will be evaluated by comparing disease control assessments at weeks 0 and 52. Secondary endpoints include changes in SNOT-22, ACQ, and smell test scores from baseline to 52 weeks, as well as changes in disease control assessments by the given drug. The expected length of participant involvement is up to 52 weeks, with conditions for early termination including significant adverse events or failure to maintain partly controlled disease status. The trial is categorized as a Phase IV clinical trial and is considered low intervention, focusing on the real-world application of biologic therapies in CRSwNP management.

The clinical trial involves the use of two **experimental medications**: **Dupilumab** and **Mepolizumab**, both administered as a solution for injection in pre-filled syringes. **Dupilumab** is a monoclonal antibody with the active substance name **Dupilumab** (also known by synonyms **REGN668** and **SAR231893**). It is classified under the ATC code **D11AH05**. The pharmaceutical form is identified as **PHF00231MIG**. The maximum daily dose for **Dupilumab** is 300 mg, with a total maximum dose of 3900 mg over a treatment period of up to 52 weeks. The administration route is subcutaneous injection, and the dosing frequency is determined based on the study protocol, with compliance monitored throughout the trial.

**Mepolizumab** is another monoclonal antibody used in this study, with the active substance name **Mepolizumab** (also known by the synonym **SB240563**). It is classified under the ATC code **R03DX09**. The pharmaceutical form is identified as **PHF00201MIG**. The maximum daily dose for **Mepolizumab** is 100 mg, with a total maximum dose of 1300 mg over a treatment period of up to 52 weeks. Similar to **Dupilumab**, **Mepolizumab** is administered via subcutaneous injection, with the dosing schedule and participant compliance closely monitored as per the study protocol.

Both medications are used in the context of tapering biologics in patients with severe **chronic rhinosinusitis with nasal polyposis** (CRSwNP) who have demonstrated stable, partly controlled disease. The trial aims to evaluate the impact of prolonged dosing intervals after 12 months of partly controlled disease. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial documentation. The study's primary outcome is to assess the percentage of patients achieving sustained partly controlled disease after tapering the biologics over a 52-week period.

Efficacy in this clinical trial will be assessed by evaluating the impact of prolonged dosing intervals of biologic therapy in patients with severe chronic rhinosinusitis with nasal polyposis (CRSwNP) who have demonstrated stable, partly controlled disease. The primary endpoint is the percentage of patients achieving sustained partly controlled disease after tapering of biologics, specifically **Mepolizumab** or **Dupilumab**, over a 52-week period. This will be determined by comparing disease control assessments at baseline (week 0) and at the end of the study (week 52).

The primary endpoint will be evaluated based on the presence of 1-2 of the following seven items: nasal blockage present on most days of the week, mucopurulent rhinorrhoea/postnasal drip on most days, facial pain/pressure present on most days, impaired sense of smell, sleep disturbance or fatigue, diseased mucosa observed in nasal endoscopy, and the need for one course of rescue treatment (systemic corticosteroids, endoscopic sinus surgery, or antibiotics).

Secondary endpoints include changes in SNOT-22, ACQ, and smell test scores from baseline to 52 weeks, as well as changes in disease control assessments by the given drug over the same period. Additionally, baseline and demographic data such as age, sex, comorbidities, BMI, level of education, and duration of biologic treatment will be collected and analyzed. These assessments will provide a comprehensive evaluation of the efficacy of the biologic tapering strategy in maintaining disease control in patients with CRSwNP.