Evaluation of Nebulized BX004 in Adult Cystic Fibrosis Patients with Chronic Pseudomonas aeruginosa Pulmonary Infection: A Phase 2b Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** of nebulized BX004 on the sputum burden of **Pseudomonas aeruginosa** (PsA) in adult subjects with **cystic fibrosis** (CF) and chronic PsA pulmonary infection after 8 weeks of treatment. This is clinically relevant as reducing the PsA burden can potentially improve respiratory function and overall health outcomes in CF patients, who are often challenged by persistent and difficult-to-treat lung infections.

Secondary objectives include:

• Assessing the clinical efficacy of nebulized BX004 in terms of lung function and quality of life as reported by patients at various timepoints.
• Evaluating the efficacy of nebulized BX004 on the sputum PsA burden in CF subjects with chronic PsA pulmonary infection at various timepoints.
• Determining the efficacy of BX004 in obtaining negative sputum cultures for PsA at various timepoints.
• Assessing the safety and tolerability of nebulized BX004.

The clinical trial involves a total of **23 participants** diagnosed with **cystic fibrosis** who are experiencing chronic **Pseudomonas aeruginosa** pulmonary infection. The study population includes both male and female subjects, aged 18 years and older, with a **forced expiratory volume in one second (FEV1)** between 40-80% predicted, indicating a clinically stable lung disease. Participants are required to be on inhaled antibiotics for **Pseudomonas aeruginosa**, either as a cycling regimen, continuous regimen, or not on antibiotics at all. The selection criteria ensure that participants are willing and able to provide adequate sputum samples, either spontaneously expectorated or induced, at study visits. The trial does not include a vulnerable population, and participants are receiving standard care CF medications. The study aims to evaluate the efficacy of nebulized BX004 on sputum PsA burden over an 8-week treatment period.

The clinical trial is a **Phase 2b**, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy of nebulized bacteriophage treatment in adult patients with **cystic fibrosis** and chronic **Pseudomonas aeruginosa** pulmonary infection. The investigational product, BX004, is administered as an **inhalation solution** using the eFlow Nebulizer System. The trial aims to assess the change in sputum **Pseudomonas aeruginosa** colony-forming units (CFU) per gram at the end of an 8-week treatment period. Secondary endpoints include changes in lung function, quality of life assessments, and the incidence of treatment-emergent adverse events.

The trial is expected to commence recruitment on July 22, 2025, and conclude by September 22, 2026. Participants will be involved in the study for a maximum of 60 days, with the primary endpoint assessed at the end of this period. The study includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor treatment effects and safety, and an end-of-study visit to evaluate the primary and secondary endpoints. Participants must meet specific inclusion criteria, such as being at least 18 years old, having a **forced expiratory volume in one second (FEV1)** between 40-80% predicted, and being clinically stable. Exclusion criteria are not specified in the provided data.

Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The trial's design ensures that neither the participants nor the investigators know whether the active treatment or placebo is being administered, maintaining the study's double-blind nature. The use of a placebo control allows for a rigorous assessment of the treatment's efficacy compared to standard care. The trial's methodology and design are structured to provide robust data on the potential benefits of BX004 in managing chronic **Pseudomonas aeruginosa** infections in **cystic fibrosis** patients.

The clinical trial involves the administration of **BX004**, an investigational medication formulated as an **inhalation solution**. BX004 is composed of natural bacteriophages specifically targeting **Pseudomonas aeruginosa**, a common pathogen in patients with **cystic fibrosis**. The active substances in BX004 include IHMA-2121771-1, IHMA-2121771-2, IHMA-2121908-1, P37IHMA-2121908, and P6IHMA-2121908, all of which are structurally diverse substances. The medication is administered via inhalation using the eFIow Nebulizer System (Type 678), which is designed to deliver the investigational drug as an aerosol. The maximum daily dose is 10 ml, with a total treatment period of up to 60 days. Participant compliance is monitored through scheduled dosing and follow-up visits.

The study also includes a **placebo** group, where participants receive a placebo treatment labeled as BX004 Placebo. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo does not contain any active substances and is administered in a manner identical to the experimental treatment to ensure consistency in the study protocol.

The efficacy of the investigational product, BX004, will be assessed in a Phase 2b, randomized, double-blind, placebo-controlled, multicenter study. The primary endpoint for evaluating efficacy is the change from baseline in **Pseudomonas aeruginosa** (PsA) colony-forming units per gram (CFU/g) of sputum at 8 weeks of treatment, which corresponds to the end of treatment (EOT). Secondary endpoints include changes from baseline in lung function, specifically the percentage of predicted forced expiratory volume in one second (FEV1), and quality of life assessments using the Cystic Fibrosis Questionnaire - Revised (CFQ-R) respiratory domain, as well as the Cystic Fibrosis Respiratory Symptom Diary and Chronic Respiratory Infection Symptom Score (CFRSD-CRISS). Additional secondary endpoints involve changes in PsA CFU/g of sputum at study visits, efficacy of BX004 on sputum culture conversion, and the incidence of treatment-emergent adverse events, along with changes in vital signs, lung exams, blood tests, and spirometry.

The efficacy parameters will be measured and collected at specified study visits throughout the trial. The primary endpoint will be assessed at the end of the 8-week treatment period. Secondary endpoints will be evaluated at various timepoints during the study to monitor changes from baseline. The eFlow Nebulizer System (Type 678) will be utilized to administer the investigational drug product as an aerosol for inhalation. This device is intended to ensure consistent delivery of the nebulized bacteriophage treatment to the participants. The data collected will be analyzed to determine the efficacy of BX004 in reducing the PsA burden in cystic fibrosis patients with chronic PsA pulmonary infection.