Evaluation of Benralizumab Efficacy and Safety in Eosinophilic Asthma Patients Uncontrolled on Medium-Dose ICS-LABA Therapy

The primary objective of this study is to evaluate the **efficacy** and **safety** of **benralizumab** in patients with **eosinophilic asthma** who remain uncontrolled on medium-dose inhaled corticosteroids (ICS) combined with long-acting beta-2 agonists (LABA). The study aims to compare the outcomes of adding benralizumab to the existing treatment regimen versus escalating therapy to high-dose ICS-LABA. This is clinically relevant as it addresses the management of eosinophilic asthma, a condition characterized by persistent symptoms and frequent exacerbations despite standard treatment, potentially improving patient outcomes and quality of life.

The clinical trial involves a total of **228 participants** diagnosed with **eosinophilic asthma**. The study population includes both male and female subjects, aged between **18 to 75 years**. Participants were selected based on specific criteria, including a documented history of physician-diagnosed asthma requiring treatment with at least medium-dose inhaled corticosteroids (ICS) and a long-acting beta-agonist (LABA) for at least 12 months prior to the study. The trial does not include a vulnerable population. Participants are required to have a peripheral blood eosinophil count of ≥ 150 cells/μL and a weight of ≥ 35 kg. They must also have experienced at least two asthma exacerbations in the 12 months prior to the study and demonstrate at least 70% compliance with their usual asthma controller medication during the run-in period. The study does not impose specific lifestyle considerations such as diet or physical activity, focusing instead on the medical history and current health status related to asthma management.

The clinical trial is designed as a **randomized**, **double-blind**, parallel-group, active-controlled, Phase 3b study to evaluate the efficacy and safety of **benralizumab** 30 mg administered subcutaneously in patients with **eosinophilic asthma** who are uncontrolled on medium-dose inhaled corticosteroid (ICS) plus long-acting beta-2 agonist (LABA). The trial aims to compare the add-on therapy of benralizumab with escalation therapy using high-dose ICS-LABA. The study is expected to commence recruitment on March 31, 2025, and conclude by October 16, 2027, with a total duration of 48 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, asthma history, and blood eosinophil count. Following the screening, eligible participants will enter a run-in period to ensure compliance with asthma controller medications. The primary endpoint of the study is the annual asthma exacerbation rate (AAER) during the 48-week treatment period, with secondary endpoints including changes in the St. George's Respiratory Questionnaire (SGRQ) total score from baseline to the end of treatment.

Study visits will include regular follow-up assessments to monitor safety and efficacy, with the final visit marking the end of the study. Participants are expected to be involved for the entire 48-week duration unless early termination is warranted due to adverse events, non-compliance, or withdrawal of consent. The trial will adhere to rigorous methodological standards to ensure the reliability and validity of the findings, contributing valuable insights into the management of eosinophilic asthma.

The clinical trial involves the administration of several treatments to evaluate the efficacy and safety of **benralizumab** in patients with eosinophilic asthma. The primary experimental medication is **Fasenra**, which contains **benralizumab** as the active substance. Fasenra is provided as a 30 mg solution for injection in a pre-filled syringe. The pharmaceutical form is a solution for injection, and it is administered via the subcutaneous route. The dosing schedule involves administration every four weeks for the first three doses, followed by administration every eight weeks. The product is manually assembled, packaged, labeled, and released by AstraZeneca prior to use, utilizing an accessorized pre-filled syringe.

In addition to the experimental medication, a **placebo** for benralizumab is used in the study. The placebo is designed to match the experimental treatment in appearance and administration method but does not contain the active substance. The placebo is administered subcutaneously at the same frequency as the active treatment to maintain blinding in the study.

The study also includes the use of **Symbicort Turbuhaler**, which is a standard-of-care therapy for asthma. Symbicort Turbuhaler is available in two formulations: 160 micrograms/4.5 micrograms per inhalation and 320 micrograms/9 micrograms per inhalation. The active substances in Symbicort are **budesonide** and **formoterol fumarate dihydrate**. The pharmaceutical form is an inhalation powder, and it is administered via inhalation. The Turbuhaler is packed, labeled, and released by AstraZeneca, with a white turning grip for blinding purposes, differing from the commercial product's red grip.

Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment regimen. The trial aims to compare the efficacy of add-on benralizumab therapy versus escalation therapy with high-dose inhaled corticosteroid plus long-acting β2 agonist (ICS-LABA) in patients with eosinophilic asthma uncontrolled on medium-dose ICS-LABA.

The efficacy of the clinical trial will be assessed using specific endpoints designed to evaluate the impact of **benralizumab** in patients with eosinophilic asthma who are uncontrolled on medium-dose inhaled corticosteroid plus long-acting β2 agonist (ICS-LABA). The primary endpoint for efficacy evaluation is the annual asthma exacerbation rate (AAER) during the 48-week treatment period. This endpoint will provide a quantitative measure of the frequency of asthma exacerbations experienced by participants over the course of the study.

Secondary endpoints include the change from baseline in the St. George's Respiratory Questionnaire (SGRQ) total score to the end of treatment (EOT) at Week 48. The SGRQ is a validated tool used to assess health-related quality of life in patients with diseases of airway obstruction, providing insights into the impact of the treatment on the patient's daily life and well-being.

Data collection for these endpoints will occur at specified timepoints throughout the trial, with the primary endpoint being assessed continuously over the 48-week period, and the secondary endpoint being evaluated at the conclusion of the treatment phase. The analysis of these endpoints will involve statistical methods appropriate for the data type and distribution, ensuring robust and reliable conclusions regarding the efficacy of benralizumab in the target patient population.