Efficacy and Safety of Benralizumab in Severe Eosinophilic Chronic Rhinosinusitis with Nasal Polyps and Asthma: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the effect of **benralizumab** on nasal polyp burden, as assessed by nasal endoscopy, and on patient-reported nasal blockage in patients with Eosinophilic Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). This is clinically relevant as nasal polyps and blockage significantly impact the quality of life and respiratory function in affected individuals.

Secondary objectives include evaluating the effect of benralizumab on:

• Sense of smell
• Sinus opacification by computed tomography (CT) scan
• Disease-specific health-related quality of life (HRQoL)
• Nasal polyp surgery
• Systemic corticosteroid (SCS) use
• Symptoms associated with CRSwNP
• Nasal polyp surgery and/or systemic corticosteroids (SCS) use for relief of nasal symptoms

The clinical trial involves a total of **216 participants** diagnosed with **severe chronic rhinosinusitis with nasal polyps (CRSwNP)** and asthma. The study population comprises both male and female patients aged between 18 to 75 years. Participants were selected based on specific criteria, including a history of treatment with systemic corticosteroids or prior surgery for CRSwNP, and a documented physician-diagnosed asthma. All participants are required to have a blood eosinophil count of greater than 2% or at least 150/μL at enrollment. They must have been using stable intranasal corticosteroids for at least four weeks prior to enrollment and throughout the screening period. The trial includes individuals with ongoing symptoms for at least 12 weeks prior to enrollment, a bilateral sinonasal polyposis with a nasal polyp score of 5 at enrollment and randomization, and a patient-reported moderate to severe nasal blockage score of 2 or more at enrollment. Additionally, participants must have a SNOT-22 total score of 20 or higher at both enrollment and randomization. The trial does not exclude vulnerable populations, and lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.

The clinical trial is designed as a **randomized**, **double-blind**, placebo-controlled, parallel-group study to evaluate the efficacy and safety of **benralizumab** in patients with **eosinophilic chronic rhinosinusitis with nasal polyps**. The trial aims to assess the effect of benralizumab on nasal polyp burden and patient-reported nasal blockage. The study is expected to run from November 2021 to September 2025, with participant involvement lasting up to 112 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, blood eosinophil count, and history of treatment for chronic rhinosinusitis with nasal polyps. Following randomization, participants will receive either benralizumab or placebo via subcutaneous injection. The trial includes regular follow-up visits to monitor safety and efficacy endpoints, such as changes in nasal polyp score and nasal blockage score. The end-of-study visit will conclude the participant's involvement, assessing the overall outcomes and any adverse events.

Participants may be withdrawn from the study early if they experience significant adverse effects, fail to adhere to the study protocol, or if the investigator deems it necessary for their safety. The primary endpoints include changes from baseline in endoscopic total nasal polyp score and mean nasal blockage score. Secondary endpoints involve changes in difficulty with sense of smell, Lund Mackay score, and SinoNasal Outcome Test score, among others. The trial's rigorous design ensures that the data collected will provide valuable insights into the treatment of severe chronic rhinosinusitis with nasal polyps.

The clinical trial involves the administration of several treatments, including **Mometasone Furoate** nasal sprays and **Benralizumab** injections, as well as a placebo. The first experimental medication, **Mometasonfuroaat Teva 50 microgram/verstuiving, neusspray, suspensie**, is a **nasal spray, suspension** containing the active substance **Mometasone Furoate**. It is administered via nasal spray with a maximum daily dose of 400 micrograms. The treatment period for this medication is up to 60 days. The product is manufactured by TEVA NEDERLAND B.V. and is not a pediatric formulation.

The second experimental medication, **Mometasonfuroat-ratiopharm® 50 Mikrogramm/Sprühstoß Nasenspray, Suspension**, also contains **Mometasone Furoate** and is administered as a **nasal spray, suspension**. Similar to the first nasal spray, it has a maximum daily dose of 400 micrograms and a treatment period of up to 60 days. This product is manufactured by RATIOPHARM GMBH and is also not a pediatric formulation.

The trial also includes a placebo, which is a sterile liquid solution presented in an accessorized prefilled syringe for subcutaneous injection. This placebo is used to compare the efficacy and safety of the experimental treatments. It is important to note that the placebo does not contain any active substance and is used to maintain the double-blind nature of the study.

The primary experimental treatment in this trial is **Fasenra 30 mg solution for injection in pre-filled syringe**, containing the active substance **Benralizumab**. This medication is administered via subcutaneous injection with a maximum total dose of 240 milligrams over a treatment period of 112 days. The product is manufactured by ASTRAZENECA AB and involves clinical packaging that is manually assembled, packaged, and labeled. This treatment is not a pediatric formulation and is used to evaluate its effect on nasal polyp burden and patient-reported nasal blockage in patients with eosinophilic chronic rhinosinusitis with nasal polyps.

Efficacy in the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoints include the change from baseline in the endoscopic total nasal polyp score (NPS) and the change from baseline in the mean nasal blockage score (NBS). These parameters will be measured to evaluate the effect of **benralizumab** on nasal polyp burden and patient-reported nasal blockage in patients with eosinophilic chronic rhinosinusitis with nasal polyps.

Secondary endpoints will further assess efficacy through various measures, including the change from baseline in difficulty with sense of smell (DSS) score, change from baseline in Lund Mackay score, and change from baseline in SinoNasal Outcome Test (SNOT-22) score. Additionally, the time to first nasal polyp surgery and the time to first systemic corticosteroid (SCS) course for nasal polyps will be evaluated. Other secondary measures include the change from baseline in nasal symptom scores, the time to first nasal polyp surgery and/or SCS use for chronic rhinosinusitis with nasal polyps (CRSwNP), and the proportion of patients requiring nasal polyp surgery and/or SCS use for CRSwNP.