Efficacy and Safety Evaluation of Lebrikizumab in Chronic Rhinosinusitis with Nasal Polyps on Intranasal Corticosteroids: A Phase 3 Randomized Controlled Trial

The primary objective of this Phase 3, multicenter, randomized, double-blind, placebo-controlled study is to evaluate the **efficacy** of **lebrikizumab** compared to placebo in reducing nasal congestion severity and endoscopic nasal polyp score (NPS) in participants with **Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)** who are on background intranasal corticosteroids (INCS) at Week 24. This objective is clinically relevant as it aims to address the persistent symptoms and improve the quality of life in patients suffering from CRSwNP, a condition characterized by inflammation of the nasal passages and the presence of nasal polyps, which can lead to significant morbidity.

The clinical trial investigating the efficacy of lebrikizumab in patients with **Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)** includes a total of 294 participants. The study population comprises both male and female subjects, with an age range that includes adults and adolescents. Participants were selected based on specific criteria, including a physician-diagnosed chronic rhinosinusitis with bilateral nasal polyps, prior treatment with systemic corticosteroids or surgery for nasal polyps, and ongoing symptoms for at least eight weeks prior to study entry. The trial also considers individuals with stable asthma, provided they have been on permitted regular asthma treatment for the three months preceding screening. The study population includes a vulnerable group, ensuring a comprehensive evaluation of the treatment's efficacy across different demographics. Lifestyle factors such as diet and physical activity are not specified, focusing instead on the medical history and current health status related to CRSwNP.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of **lebrikizumab** in participants with **chronic rhinosinusitis with nasal polyps** (CRSwNP) who are on background intranasal corticosteroids. The trial will involve a parallel group design and is classified as a Phase III study. The estimated duration of the trial is approximately two years, with recruitment expected to start in September 2024 and the study concluding by October 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a physician-diagnosed CRSwNP, prior treatment history, and symptom severity. Following successful screening, participants will be randomized to receive either lebrikizumab or a placebo, administered via subcutaneous injection, alongside their ongoing intranasal corticosteroid treatment. The primary endpoints include the mean change from baseline in participant-reported nasal congestion score and endoscopic nasal polyp score at Week 24.

Study visits will be scheduled at regular intervals to monitor the participants' health status, treatment adherence, and response to the intervention. These visits will include assessments of nasal congestion severity and nasal polyp size, as well as safety evaluations. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted to gather comprehensive data on the treatment's efficacy and safety.

Participant involvement is expected to last for the duration of the trial, with specific conditions outlined for early termination. These conditions may include adverse events, non-compliance with the study protocol, or withdrawal of consent. The trial aims to provide robust data on the potential benefits of lebrikizumab in managing CRSwNP, contributing to the understanding of its therapeutic role in this patient population.

The clinical trial involves the administration of **Lebrikizumab**, a monoclonal antibody, as the experimental medication. Lebrikizumab is provided in the form of a **solution for injection** and is administered via **subcutaneous injection**. The pharmaceutical form is a pre-filled syringe with a needle safety device. The dosing schedule and frequency of administration are not specified in the provided data. Participant compliance with the dosing regimen will be monitored throughout the study to ensure adherence to the protocol.

A **placebo** is used as a comparator treatment in this study. The placebo is designed to match the appearance and administration route of Lebrikizumab, ensuring the study remains double-blind. The placebo is administered via subcutaneous injection, similar to the experimental medication. The pharmaceutical form and specific dosing schedule for the placebo are not detailed in the provided data.

In addition to the experimental and placebo treatments, participants will receive **Mometasone Furoate** as a background therapy. Mometasone Furoate is an intranasal corticosteroid provided in the form of a **nasal spray**. The pharmaceutical form is identified as PHF00149MIG. The administration of Mometasone Furoate will follow the standard-of-care dosing regimen, although specific dosing details are not provided. This background therapy is intended to maintain a consistent level of intranasal corticosteroid treatment across all study participants.

The efficacy of **lebrikizumab** in the treatment of chronic rhinosinusitis with nasal polyps will be assessed through primary endpoints focusing on symptom severity and polyp size. The primary efficacy parameters include the mean change from baseline in the participant-reported Nasal Congestion Score (NCS) severity and the Endoscopic Nasal Polyp Score (NPS). The NCS severity is evaluated by participants using a 4-point scale, ranging from 0 (no symptoms) to 3 (severe symptoms), with assessments recorded in an electronic diary (eDiary) at baseline and at Week 24. The NPS is determined through a centralized, blinded, independent review of nasal endoscopy video recordings, with scores ranging from 0 (no polyps) to 4 (large polyps) for each nasal cavity, also assessed at baseline and Week 24.