Clinical trial NCT04684641: CYstic Fibrosis bacterioPHage Study at Yale (CYPHY)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cystic Fibrosis
Keywords: Pseudomonas
bacteriophage
phage
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2020-12-24
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Capable of giving signed informed consent;
2. Stated willingness to comply with all study procedures and availability for the duration of the study;
3. Age ≥18;
4. CF diagnosis based upon genetics, sweat chloride testing, or clinical manifestations;
5. Able to provide repeated induced sputum samples;
6. Able to use a nebulizer;
7. PsA culture positive on one occasions within past 2 years and in sputum at screening visit;
8. FEV1 \>40%;
9. Clinically stable lung disease, defined as no decrease in FEV1 \>10% or pulmonary exacerbations in the 4 weeks prior to screening;
10. 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;
11. 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;
12. 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:

1. History of solid organ transplant (e.g., lung or liver);
2. Severe neutropenia, as defined by absolute neutrophil count (ANC) of \< 500 per microliter;
3. No YPT-01 phage identified that effectively targets sputum PsA;
4. Treatment for pulmonary exacerbation within the prior 4 weeks;
5. Change in pulmonary medications within the prior 4 weeks;
6. Subjects who are pregnant, who intend to become pregnant, or who do not wish to use contraception;
7. Subjects who are breastfeeding;
8. Participation in another clinical research study concurrently or within the prior 2 months;
9. Known allergy to soy, egg, yeast, or meat.
10. Any genetic or acquired (including medication-induced) immunocompromised condition, beyond the level of immunocompromise typically associated with CF and its management.

Primary outcomes:
measure: Change in Sputum Bacterial Culture
timeFrame: Day 14
Secondary outcomes:
measure: Change in Lung Function
timeFrame: Screening, day 14, day 21, day 28, and day 56
measure: Difference in the Rate of Pulmonary Exacerbations
timeFrame: Baseline, day 56
measure: Difference in the Rate of Hospitalization
timeFrame: Baseline, day 56
measure: Difference in the Rate of Acute Antibiotic Use
timeFrame: Baseline, day 56
measure: Patient's Quality of Life
timeFrame: Baseline, day 56
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
Study officials:
affiliation: Yale University
name: Jonathan Koff, MD
role: STUDY_DIRECTOR
affiliation: Yale University
name: Benjamin Chan, PhD
role: PRINCIPAL_INVESTIGATOR
References: