Efficacy and Safety Evaluation of PF-07275315 in Adults with Moderate-to-Severe Asthma: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** of PF-07275315 compared to placebo in participants with moderate-to-severe asthma and with eosinophil counts ≥300 cells/μL. This is clinically relevant as it aims to determine the potential of PF-07275315 to improve asthma control in a specific subgroup of patients characterized by elevated eosinophil levels, which are often associated with more severe asthma symptoms and exacerbations.

Secondary objectives include:

• Assessing additional efficacy measures of PF-07275315 compared to placebo in participants with moderate-to-severe asthma and with eosinophil counts ≥300 cells/μL.
• Evaluating the efficacy of PF-07275315 compared to placebo in participants with moderate-to-severe asthma and with eosinophil counts <300 cells/μL.
• Assessing the efficacy of PF-07275315 compared to placebo in participants with moderate-to-severe asthma, irrespective of baseline eosinophil counts.
• Evaluating the effect on quality of life of PF-07275315 in participants with moderate-to-severe asthma and with eosinophil counts ≥300 cells/μL.
• Assessing the efficacy of PF-07275315 compared to placebo in participants with moderate-to-severe asthma and with FeNO ≥25 ppb and <25 ppb.

The clinical trial involves a total of **162 participants** diagnosed with **moderate-to-severe asthma**. The study population includes both male and female subjects, aged between **18 to 70 years**, who have a documented history of persistent asthma for at least 12 months prior to screening. Participants were selected based on specific criteria, including a history of asthma exacerbations requiring systemic steroid treatment and a positive bronchodilator responsiveness test. The trial excludes vulnerable populations. All participants are required to have been on a stable regimen of medium to high dose inhaled corticosteroids combined with long-acting beta 2 agonists for at least 12 months before the screening. The body mass index of participants ranges from 18 to 40 kg/m². Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The trial aims to assess the efficacy and safety of PF-07275315 compared to placebo in this specific population.

The clinical trial is a **randomized**, **double-blind**, **placebo-controlled** study designed to evaluate the efficacy and safety of PF-07275315 in adult participants with inadequately controlled moderate-to-severe **asthma**. The trial will involve a parallel-group, dose-ranging approach to assess the primary and secondary endpoints over a period of 12 weeks. The study will commence with a screening visit to confirm eligibility based on specific inclusion criteria, such as age, history of asthma, and bronchodilator responsiveness. Participants will be randomly assigned to receive either the investigational product, PF-07275315, administered as a **subcutaneous injection**, or a placebo. The trial will include several follow-up visits to monitor the participants' health status, collect data on lung function, and record any treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs).

The primary endpoints include the change from baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) at Week 12, and the incidence of TEAEs and SAEs. Secondary endpoints will assess additional lung function parameters and quality of life measures. Participants will be involved in the study for approximately 12 weeks, with the possibility of early termination if they experience significant adverse events or fail to adhere to the study protocol. The trial is expected to conclude by July 2027, with recruitment starting in November 2025. The study aims to provide valuable insights into the potential benefits and risks of PF-07275315 for individuals with moderate-to-severe asthma, contributing to the development of more effective treatment options for this condition.

The clinical trial involves the administration of **PF-07275315**, an investigational biologic agent, formulated as a **solution for injection**. The active substance, PF-07275315, is a protein of other origin, developed by Pfizer Inc. The medication is administered via **subcutaneous injection**. The dosing regimen includes a maximum daily dose of 800 mg and a total maximum dose of 3900 mg over a treatment period of up to 12 weeks. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in this double-blind, placebo-controlled study. The placebo, named PF-07275315 Placebo, is designed to match the experimental medication in appearance and administration route, ensuring the integrity of the blinding process. The placebo is administered subcutaneously, following the same schedule as the active treatment, to maintain consistency across study arms.

The efficacy of PF-07275315 in the treatment of moderate-to-severe asthma will be assessed through a series of primary and secondary endpoints. The primary efficacy endpoint is the change from baseline in pre-bronchodilator forced expiratory volume in one second (**FEV1**) at Week 12. This measurement will be used to evaluate the improvement in lung function. Secondary endpoints include changes from baseline in pre-bronchodilator percentage predicted FEV1 at Week 12, as well as other lung function parameters such as forced vital capacity (FVC) and the FEV1/FVC ratio at various time points. Additionally, changes in the asthma control questionnaire (ACQ-5) total score and the asthma quality of life questionnaire with standardized activities (AQLQ) global score at Week 12 will be assessed to evaluate symptom control and quality of life improvements.

Data collection will occur at specified intervals, with key assessments at Week 12. The efficacy parameters will be measured using validated spirometry techniques for lung function and standardized questionnaires for patient-reported outcomes. The analysis will focus on comparing the changes from baseline between the treatment group receiving PF-07275315 and the placebo group. The study is designed to ensure rigorous evaluation of the treatment's impact on asthma control and patient quality of life.