Cystic Fibrosis
Conditions
Keywords
Pseudomonas, bacteriophage, phage
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.
Interventions
DRUGStandard Dose YPT-01
Participants will be randomized to receive the standard dose of phage therapy YPT-01.
OTHERPlacebo
Participants will be randomized to receive the placebo.
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sputum Bacterial Culture | Day 14 | Change in sputum bacterial culture titers of Pseudomonas as measured by colony forming units/mL at day 14 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Lung Function | Screening, day 14, day 21, day 28, and day 56 | 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 |
| Difference in the Rate of Pulmonary Exacerbations | Baseline, day 56 | Compare the rates of pulmonary exacerbations between subjects randomized to phage therapy versus placebo during the first 56 days of the study |
| Difference in the Rate of Hospitalization | Baseline, day 56 | Compare the rates of hospitalizations between subjects randomized to phage therapy versus placebo during the first 56 days of the study |
| Difference in the Rate of Acute Antibiotic Use | Baseline, day 56 | Compare the rates of acute antibiotic use between subjects randomized to phage therapy versus placebo during the first 56 days of the study |
| Patient's Quality of Life | Baseline, day 56 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phage Therapy Participants will be randomized to receive 3mL phage therapy, nebulized daily for 7 days.
Standard Dose YPT-01: Participants will be randomized to receive the standard dose of phage therapy YPT-01. | 4 |
| Placebo Participants will be randomized to receive the 3mL placebo, nebulized daily for 7 days.
Placebo: Participants will be randomized to receive the placebo. | 4 |
| Total | 8 |
Baseline characteristics
| Characteristic | Phage Therapy | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 3 Participants | 5 Participants |
| Age, Continuous | 50.50 Years STANDARD_DEVIATION 24.96 | 49.50 Years STANDARD_DEVIATION 18.27 | 50.00 Years STANDARD_DEVIATION 20.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 4 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 4 Participants | 8 Participants |
| Region of Enrollment United States | 4 participants | 4 participants | 8 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 4 / 4 | 4 / 4 |
| serious Total, serious adverse events | 1 / 4 | 1 / 4 |
Outcome results
Primary
Change in Sputum Bacterial Culture
Change in sputum bacterial culture titers of Pseudomonas as measured by colony forming units/mL at day 14
Time frame: Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phage Therapy | Change in Sputum Bacterial Culture | -0.59 CFU/mL | Standard Deviation 1.62 |
| Placebo | Change in Sputum Bacterial Culture | -0.89 CFU/mL | Standard Deviation 1.77 |
Secondary
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
Time frame: Screening, day 14, day 21, day 28, and day 56
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phage Therapy | Change in Lung Function | Change in FEV1pp from Screening to Day 28 | -1.50 FEV1pp | Standard Deviation 4.2 |
| Phage Therapy | Change in Lung Function | Change in FEV1pp from Screening to Day 21 | -3.25 FEV1pp | Standard Deviation 3.5 |
| Phage Therapy | Change in Lung Function | Change in FEV1pp from Screening to Day 56 | -1.00 FEV1pp | Standard Deviation 2.65 |
| Phage Therapy | Change in Lung Function | Change in FEV1pp from Screening to Day 14 | -1.25 FEV1pp | Standard Deviation 4.65 |
| Placebo | Change in Lung Function | Change in FEV1pp from Screening to Day 56 | -1.00 FEV1pp | Standard Deviation 9.9 |
| Placebo | Change in Lung Function | Change in FEV1pp from Screening to Day 21 | 0.00 FEV1pp | Standard Deviation 4.36 |
| Placebo | Change in Lung Function | Change in FEV1pp from Screening to Day 28 | 0.25 FEV1pp | Standard Deviation 4.11 |
| Placebo | Change in Lung Function | Change in FEV1pp from Screening to Day 14 | 0.50 FEV1pp | Standard Deviation 1.29 |
Secondary
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
Time frame: Baseline, day 56
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phage Therapy | Difference in the Rate of Acute Antibiotic Use | 1 Instance(s) of acute antibiotic use |
| Placebo | Difference in the Rate of Acute Antibiotic Use | 1 Instance(s) of acute antibiotic use |
Secondary
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
Time frame: Baseline, day 56
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phage Therapy | Difference in the Rate of Hospitalization | 0 Count of Hospitalization(s) |
| Placebo | Difference in the Rate of Hospitalization | 1 Count of Hospitalization(s) |
Secondary
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
Time frame: Baseline, day 56
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phage Therapy | Difference in the Rate of Pulmonary Exacerbations | 1 Count of Pulmonary Exacerbation(s) |
| Placebo | Difference in the Rate of Pulmonary Exacerbations | 1 Count of Pulmonary Exacerbation(s) |
Secondary
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.
Time frame: Baseline, day 56
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phage Therapy | Patient's Quality of Life | Physical | -6.25 Change in CFQR score from baseline | Standard Deviation 12.95 |
| Phage Therapy | Patient's Quality of Life | Vitality | -12.50 Change in CFQR score from baseline | Standard Deviation 17.35 |
| Phage Therapy | Patient's Quality of Life | Emotion | -8.33 Change in CFQR score from baseline | Standard Deviation 3.33 |
| Phage Therapy | Patient's Quality of Life | Eat | 2.78 Change in CFQR score from baseline | Standard Deviation 5.56 |
| Phage Therapy | Patient's Quality of Life | Treatment Burden | -2.78 Change in CFQR score from baseline | Standard Deviation 16.67 |
| Phage Therapy | Patient's Quality of Life | Health Perceptions | -8.33 Change in CFQR score from baseline | Standard Deviation 5.56 |
| Phage Therapy | Patient's Quality of Life | Social | 1.39 Change in CFQR score from baseline | Standard Deviation 9.49 |
| Phage Therapy | Patient's Quality of Life | Body | 0.00 Change in CFQR score from baseline | Standard Deviation 9.07 |
| Phage Therapy | Patient's Quality of Life | Role | -8.33 Change in CFQR score from baseline | Standard Deviation 11.79 |
| Phage Therapy | Patient's Quality of Life | Weight | 0.00 Change in CFQR score from baseline | Standard Deviation 0 |
| Phage Therapy | Patient's Quality of Life | Respiratory | -5.56 Change in CFQR score from baseline | Standard Deviation 16.36 |
| Phage Therapy | Patient's Quality of Life | Digestion | 0.00 Change in CFQR score from baseline | Standard Deviation 0 |
| Placebo | Patient's Quality of Life | Respiratory | -4.17 Change in CFQR score from baseline | Standard Deviation 13.89 |
| Placebo | Patient's Quality of Life | Physical | 0.00 Change in CFQR score from baseline | Standard Deviation 22.82 |
| Placebo | Patient's Quality of Life | Social | -2.78 Change in CFQR score from baseline | Standard Deviation 7.17 |
| Placebo | Patient's Quality of Life | Vitality | -2.08 Change in CFQR score from baseline | Standard Deviation 21.92 |
| Placebo | Patient's Quality of Life | Weight | 0.00 Change in CFQR score from baseline | Standard Deviation 0 |
| Placebo | Patient's Quality of Life | Emotion | -10.00 Change in CFQR score from baseline | Standard Deviation 20 |
| Placebo | Patient's Quality of Life | Body | 0.00 Change in CFQR score from baseline | Standard Deviation 0 |
| Placebo | Patient's Quality of Life | Eat | -16.67 Change in CFQR score from baseline | Standard Deviation 26.45 |
| Placebo | Patient's Quality of Life | Digestion | -8.33 Change in CFQR score from baseline | Standard Deviation 16.66666667 |
| Placebo | Patient's Quality of Life | Treatment Burden | -8.33 Change in CFQR score from baseline | Standard Deviation 31.91 |
| Placebo | Patient's Quality of Life | Role | -4.17 Change in CFQR score from baseline | Standard Deviation 4.81 |
| Placebo | Patient's Quality of Life | Health Perceptions | 11.11 Change in CFQR score from baseline | Standard Deviation 24 |