Nebulized Bacteriophage Therapy in Cystic Fibrosis Patients With Chronic Pseudomonas Aeruginosa Pulmonary Infection

Study Overview
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Brief Summary
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This is a Phase 1b/2a study with the primary objective to determine if BX004-A is safe and tolerable. Exploratory objectives include whether BX004-A reduces sputum Pseudomonas aeruginosa (PsA) bacterial load in CF subjects with chronic PsA pulmonary infection.

Detailed Description
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This is a randomized, double-blind, placebo-controlled, multicenter study to evaluate the safety and tolerability of BX004-A in CF subjects with chronic PsA pulmonary infection. The study is divided into two parts, a single-ascending and multiple-dose phase (Part 1) and a multiple dose phase (Part 2). Subjects in both parts will be included in a 6-month safety follow-up. A Data Safety Monitoring Board will monitor safety in both parts. The purpose of the study is to evaluate safety and tolerability of BX004-A, and whether BX004-A reduces the PsA burden in the sputum of CF subjects with chronic PsA pulmonary infection. Clinically stable CF subjects with a confirmed diagnosis of CF and chronic PsA pulmonary infection will be enrolled.

Official Title
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A Phase 1b/2a, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate Nebulized Bacteriophage Treatment in Outpatient Adult Cystic Fibrosis (CF) Subjects With Chronic Pseudomonas Aeruginosa (PsA) Pulmonary Infection

Conditions
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Chronic Pseudomonas Aeruginosa Infection, Cystic Fibrosis

Intervention / Treatment
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* Drug: BX004-A
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Cystic fibrosis patients with chronic Pseudomonas aeruginosa pulmonary infection receiving standard of care CF medications Age ≥ 18 years FEV1 ≥ 40% predicted Clinically stable lung disease Willing and able to provide adequate sputum samples, using any method (spontaneously expectorated, induced, from home or clinic) at designated study visits. Key Exclusion Criteria: Known hypersensitivity to bacteriophages or excipients in the formulation. Receipt of prior bacteriophage therapy within the 6 months prior to Screening Recovery of Burkholderia species from respiratory tract within 1 year prior to screening Currently receiving treatment for allergic bronchopulmonary aspergillosis Currently receiving treatment for active infection with non-tuberculous mycobacteria History of severe neutropenia History of lung transplant History of solid organ transplant Acquired or primary immunodeficiency syndrome Initiation or change in CF modulator therapy less than 3 months prior to screening Pregnant or breastfeeding female

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BX004-A<br>Participants will be randomized to receive standard dose of nebulized bacteriophage | Drug: BX004-A<br>* Combination of nebulized bacteriophages targeting Pseudomonas aeruginosa<br>* Other names: Bacteriophage;|
| Placebo Comparator: Placebo<br>Participants will be randomized to receive nebulized placebo | Drug: Placebo<br>* Nebulized placebo<br>* Other names: Vehicle buffer;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | Incidence of treatment emergent adverse events following single and multiple doses of BX004-A administered by inhalation | 6 months |