Ph 1/2 Study Evaluating Safety and Tolerability of Inhaled AP-PA02 in Subjects With Chronic Pseudomonas Aeruginosa Lung Infections and Cystic Fibrosis

Study Overview
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Brief Summary
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Phase 1b/2a, double-blind, randomized, placebo-controlled, single and multiple ascending dose study to evaluate the safety, tolerability and phage recovery profile of AP-PA02 multi-bacteriophage therapeutic candidate administered by inhalation in subjects with cystic fibrosis and chronic pulmonary Pseudomonas aeruginosa (PA) infection.

Detailed Description
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The study consists of two parts. Subjects with Cystic Fibrosis and chronic pulmonary Pseudomonas aeruginosa (PA) infection will be enrolled in either Part 1 (single-ascending dose cohorts) or Part 2 (multiple-ascending dose cohorts). Part 1 will evaluate single doses of AP-PA02 at two ascending dose levels, administered by inhalation. Treatment assignment will be randomized, double-blind, placebo-controlled in each of two ascending dose cohorts. Part 2 will also be double-blinded, randomized, placebo controlled, and will evaluate the safety and efficacy of multiple doses of AP-PA02 in each of two ascending dose level cohorts. Subjects in both Parts 1 and 2 will be followed for approximately 4 weeks and evaluated for safety, tolerability, phage titer profile and immunogenicity.

Official Title
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A Phase 1b/2a, Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of AP-PA02 Multi-Phage Therapeutic Candidate for Inhalation in Subjects With Cystic Fibrosis and Chronic Pulmonary Pseudomonas Aeruginosa (Pa) Infection

Conditions
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Cystic Fibrosis, Pseudomonas Aeruginosa, Pseudomonas, Lung Infection, Lung Infection Pseudomonal

Intervention / Treatment
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* Biological: AP-PA02
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: ≥ 18 years old Body mass index (BMI) of ≥ 18 kg/m2 Documented diagnosis of CF Evidence of chronic pulmonary Pseudomonas aeruginosa infection Willing to undergo sputum induction procedures at designated study visits, and willing to provide expectorated sputum samples at all other timepoints (for subjects who are able to expectorate) For SAD: FEV1 ≥ 60% of predicted normal [per Global Lung Function Initiative (GLI) standards] at Screening For MAD: FEV1 ≥ 40% of predicted normal [per Global Lung Function Initiative (GLI) standards] at Screening Adequate renal function Key Exclusion Criteria: Recent significant weight loss Abnormal vital signs at Screening History of prolonged QT syndrome Use of supplemental oxygen during the day at rest Abnormal liver function tests greater than 3X the upper limit of normal (ULN) Recent oral or IV antibiotics received for acute pulmonary exacerbation. Inhaled antibiotic use for chronic suppression of P. aeruginosa is acceptable. Recent clinically significant infection requiring systemic antimicrobial therapy Currently receiving anti-pseudomonal antibiotic treatment for acute sinusitis. Currently receiving systemic corticosteroids Currently receiving treatment for active infection with nontuberculous mycobacteria (NTM), Staphylococcus aureus, or Burkholderia cepacia complex lung infection Currently receiving treatment for aspergillosis or ABPA (allergic bronchopulmonary aspergillosis) Initiation of a CFTR potentiator/corrector therapy, such as Trikafta®, less than 90 days prior to Screening Acquired or primary immunodeficiency syndromes Active pulmonary malignancy (primary or metastatic) History of lung transplantation Recent hemoptysis Female pregnant or breastfeeding Heavy smoker

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
Interventional Model Description: Randomized, double-blind, placebo-controlled
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AP-PA02<br>Anti-pseudomonal bacteriophage | Biological: AP-PA02<br>* Bacteriophage administered via inhalation<br>|
| Placebo Comparator: Placebo<br>Inactive isotonic solution | Other: Placebo<br>* Inactive Placebo administered via inhalation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events (Safety and Tolerability) of single and multiple doses of AP-PA02 administered by inhalation | Incidence and severity of treatment-emergent adverse events | Day 1 pre-dose through End of Study Visit (28 days post last dose of study drug) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 2 (MAD) Only: Explore P. aeruginosa recovery in sputum following multiple doses of AP-PA02 administered by inhalation | Change in P. aeruginosa colony-forming units (CFU) per gram of sputum | Baseline (Day -1) through 14 days post last dose of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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phage, bacteriophage, cystic fibrosis, Pseudomonas, Pseudomonas aeruginosa