CYstic Fibrosis bacterioPHage Study at Yale (CYPHY)

Study Overview
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Brief Summary
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This is a Phase 2 study with primary objective of looking whether YPT-01 phage therapy reduces sputum bacterial load in cystic fibrosis subjects with Pseudomonas aeruginosa. In addition, study evaluates the safety profile of phage therapy in this patient population.

Detailed Description
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This is a prospective, randomized, placebo-controlled, double-blinded, single-site study of Yale Phage Therapy (YPT) 01 in cystic fibrosis subjects with chronic Pseudomonas aeruginosa airway infections. The study has 2 parallel arms of phage therapy and placebo, with all study materials GMP-manufactured. The purpose of this study is to demonstrate efficacy and safety of inhaled (nebulized) phage therapy YPT-01. Clinically stable subjects who have confirmed diagnosis of CF with PsA in sputum cultures on at least two occasions within past year, and in sputum at screening visit, will be recruited into this study. An open-label extension is available for subjects in the placebo group to receive YPT-01 following completion of blinded portion of the study. Nov 2022 study ended enrollment after 8 subjects. The Double-Blind Randomized portion of the study was closed and the Open-Label Extension was opened.

Official Title
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CYstic Fibrosis bacterioPHage Study at Yale (CYPHY): A Single-site, Randomized, Double-blind, Placebo-controlled Study of Bacteriophage Therapy YPT-01 for Pseudomonas Aeruginosa Infections in Adults With Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Standard Dose YPT-01
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capable of giving signed informed consent; Stated willingness to comply with all study procedures and availability for the duration of the study; Age ≥18; CF diagnosis based upon genetics, sweat chloride testing, or clinical manifestations; Able to provide repeated induced sputum samples; Able to use a nebulizer; PsA culture positive on one occasions within past 2 years and in sputum at screening visit; FEV1 >40%; Clinically stable lung disease, defined as no decrease in FEV1 >10% or pulmonary exacerbations in the 4 weeks prior to screening; If on CF modulator therapy (e.g., ivacaftor, ivacaftor/elexacaftor/tezacaftor), then subject remains on the same modulator therapy for at least 2 months prior to enrollment; For females of reproductive potential: use of effective contraception for at least 1 month prior to screening and agreement to use 2 methods of effective contraception during study participation and for an additional 6 weeks after the end of YPT-01 administration; Males of non-reproductive potential (e.g., documented congenital bilateral absence of vas deferens) or males of reproductive potential (e.g., non-vasectomized males or males vasectomized less than 120 days prior to study start) that agree to use condoms with spermicide while engaging in sexual activity or be sexually abstinent. Exclusion Criteria: History of solid organ transplant (e.g., lung or liver); Severe neutropenia, as defined by absolute neutrophil count (ANC) of < 500 per microliter; No YPT-01 phage identified that effectively targets sputum PsA; Treatment for pulmonary exacerbation within the prior 4 weeks; Change in pulmonary medications within the prior 4 weeks; Subjects who are pregnant, who intend to become pregnant, or who do not wish to use contraception; Subjects who are breastfeeding; Participation in another clinical research study concurrently or within the prior 2 months; Known allergy to soy, egg, yeast, or meat. Any genetic or acquired (including medication-induced) immunocompromised condition, beyond the level of immunocompromise typically associated with CF and its management.

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: Phage therapy<br>Participants will be randomized to receive 3mL phage therapy, nebulized daily for 7 days. | Drug: Standard Dose YPT-01<br>* Participants will be randomized to receive the standard dose of phage therapy YPT-01.<br>* Other names: Phage Therapy;|
| Active Comparator: Placebo<br>Participants will be randomized to receive the 3mL placebo, nebulized daily for 7 days. | Other: Placebo<br>* Participants will be randomized to receive the placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Sputum Bacterial Culture | Change in sputum bacterial culture titers of Pseudomonas as measured by colony forming units/mL at day 14 | Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Lung Function | Change in lung function [percent predicted forced expiratory volume in 1 second (FEV1pp)] in subjects randomized to phage therapy and placebo from screening to day 14, 21, 28, and 56 | Screening, day 14, day 21, day 28, and day 56 | 
| Difference in the Rate of Pulmonary Exacerbations | Compare the rates of pulmonary exacerbations between subjects randomized to phage therapy versus placebo during the first 56 days of the study | Baseline, day 56 | 
| Difference in the Rate of Hospitalization | Compare the rates of hospitalizations between subjects randomized to phage therapy versus placebo during the first 56 days of the study | Baseline, day 56 | 
| Difference in the Rate of Acute Antibiotic Use | Compare the rates of acute antibiotic use between subjects randomized to phage therapy versus placebo during the first 56 days of the study | Baseline, day 56 | 
| Patient's Quality of Life | Changes in subject-reported quality of life, using the Cystic Fibrosis Questionnaire Revised (CFQ-R) Teen/Adult, from baseline to Day 56. This survey consists of 50 questions that relate to a subjects clinical condition and mental health. Scores for each domain range from 0 to 100, with higher scores indicating a higher patient-reported quality of life with regard to the domain being evaluated. | Baseline, day 56 | 

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