Lung Infection, Non-cystic Fibrosis Bronchiectasis, Pseudomonas Aeruginosa
Conditions
Keywords
Bacteriophage, Phage, NCFB, BE, Pseudomonas, Pseudomonas Aeruginosa
Brief summary
A phase 2, multi-center, double-blind, randomized, placebo-controlled study to evaluate the safety, phage kinetics, and efficacy of inhaled AP-PA02 administered in subjects with non-cystic fibrosis bronchiectasis and chronic pulmonary Pseudomonas aeruginosa infection.
Detailed description
This study will be conducted in two cohorts running in parallel: Cohort A will evaluate the safety, tolerability, and efficacy of inhaled AP-PA02 in subjects who have not received an antipseudomonal inhaled antibiotic for a minimum of 3 months prior. Cohort B will evaluate the safety, tolerability, and efficacy of inhaled AP-PA02 in subjects who have received an antipseudomonal inhaled antibiotic for a minimum of 3 months prior. Subjects in both Cohorts A and B will be followed for approximately 4 weeks after last dose of study drug and evaluated for safety, tolerability, and efficacy.
Interventions
BIOLOGICALAP-PA02
Bacteriophage administered via inhalation
OTHERPlacebo
Inactive Placebo administered via inhalation
Sponsors
Armata Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Double-blind, randomized, placebo-controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * ≥ 18 years old * Body mass index (BMI) of ≥ 18 kg/m2 * Evidence of bronchiectasis per CT * 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) * FEV1 ≥ 35% of predicted normal \[per Global Lung Function Initiative (GLI) standards\] at Screening * For Cohort A: have not received chronic inhaled antipseudomonal antibiotics regimen for at least 3 months prior to Visit 1 * For Cohort B: have received chronic inhaled antipseudomonal antibiotics regimen for at least 3 months prior to Visit 1 Key
Exclusion criteria
* Abnormal vital signs at Screening * History of lung transplantation * History of cystic fibrosis * History of α1-antitrypsin deficiency * History of primary or acquired immunodeficiency syndromes * History of COPD * History of pulmonary malignancy or any other malignancy requiring treatment * History of prolonged QT syndrome * History of hemoptysis * Recent significant weight loss * Recent use of supplemental oxygen during the day while at rest * Recent use of cigarettes, cigars, or pipes, or used tobacco or other nicotine source by vaping * Recent changes in either the treatment regimen or initiation of treatment with: oral macrolides, hypertonic saline, mucolytics, bronchodilator medications, or oral corticosteroids * Currently receiving treatment for active infection at any site * Female pregnant of breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| P. Aeruginosa Recovery in Sputum Following Multiple Doses of AP-PA02 Administered by Inhalation | Day 17 | Change from baseline in P. Aeruginosa density (colony forming units) as measured in induced sputum samples one week after end of treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: AP-PA02, 1.5x10^11 PFU/Dose Subjects receive AP-PA02 | 4 |
| Cohort A: AP-PA02, 3x10^11 PFU/Dose Subjects receive AP-PA02 | 19 |
| Cohort A: Placebo Subjects receive placebo | 12 |
| Cohort B: AP-PA02, 1.5x10^11 PFU/Dose Subjects receive AP-PA02 plus inhaled antibiotic | 1 |
| Cohort B: AP-PA02, 3x10^11 PFU/Dose Subjects receive AP-PA02 plus inhaled antibiotic | 9 |
| Cohort B: Placebo Subjects receive placebo plus inhaled antibiotic | 3 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort A: AP-PA02, 1.5x10^11 PFU/Dose | Total | Cohort B: Placebo | Cohort B: AP-PA02, 3x10^11 PFU/Dose | Cohort B: AP-PA02, 1.5x10^11 PFU/Dose | Cohort A: Placebo | Cohort A: AP-PA02, 3x10^11 PFU/Dose |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 66.5 years STANDARD_DEVIATION 7.85 | 64.5 years STANDARD_DEVIATION 15.53 | 53.7 years STANDARD_DEVIATION 28.43 | 64.1 years STANDARD_DEVIATION 16.24 | 75.0 years STANDARD_DEVIATION 0 | 71.7 years STANDARD_DEVIATION 11.02 | 60.9 years STANDARD_DEVIATION 16.26 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 41 Participants | 3 Participants | 7 Participants | 0 Participants | 11 Participants | 17 Participants |
| Sex: Female, Male Female | 3 Participants | 36 Participants | 3 Participants | 7 Participants | 0 Participants | 8 Participants | 15 Participants |
| Sex: Female, Male Male | 1 Participants | 12 Participants | 0 Participants | 2 Participants | 1 Participants | 4 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 19 | 0 / 12 | 0 / 1 | 0 / 9 | 0 / 3 |
| other Total, other adverse events | 4 / 4 | 15 / 19 | 5 / 12 | 0 / 1 | 7 / 9 | 1 / 3 |
| serious Total, serious adverse events | 1 / 4 | 1 / 19 | 0 / 12 | 0 / 1 | 3 / 9 | 0 / 3 |
Outcome results
Primary
P. Aeruginosa Recovery in Sputum Following Multiple Doses of AP-PA02 Administered by Inhalation
Change from baseline in P. Aeruginosa density (colony forming units) as measured in induced sputum samples one week after end of treatment.
Time frame: Day 17
Population: According to the Statistical Analysis Plan, participants who enrolled before the first DSMB meeting received a lower dose of AP-PA02 (1.5×10¹¹ PFU) and were not included in the primary analysis. In addition, two participants were excluded due to major protocol deviations related to study drug compliance. After applying these prespecified criteria, 41 participants were included in the primary outcome analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: AP-PA02, 3x10^11 PFU/Dose | P. Aeruginosa Recovery in Sputum Following Multiple Doses of AP-PA02 Administered by Inhalation | -0.5 colony forming units log10 | Standard Deviation 0.72 |
| Cohort A: Placebo | P. Aeruginosa Recovery in Sputum Following Multiple Doses of AP-PA02 Administered by Inhalation | -0.1 colony forming units log10 | Standard Deviation 1.11 |
| Cohort B: AP-PA02, 3x10^11 PFU/Dose | P. Aeruginosa Recovery in Sputum Following Multiple Doses of AP-PA02 Administered by Inhalation | -0.4 colony forming units log10 | Standard Deviation 1.63 |
| Cohort B: Placebo | P. Aeruginosa Recovery in Sputum Following Multiple Doses of AP-PA02 Administered by Inhalation | 1.0 colony forming units log10 | Standard Deviation 1.13 |
Post Hoc
Post Hoc, Pooled Analysis: P. Aeruginosa Recovery in Sputum Following Multiple Doses of AP-PA02 Administered by Inhalation
Change from baseline in P. Aeruginosa density (colony forming units) as measured in induced sputum samples one week after end of treatment.
Time frame: Day 17
Population: Post hoc analysis included all enrolled subjects, regardless of dose level or protocol deviations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A: AP-PA02, 1.5x10^11 PFU/Dose | Post Hoc, Pooled Analysis: P. Aeruginosa Recovery in Sputum Following Multiple Doses of AP-PA02 Administered by Inhalation | -0.6 colony forming units log10 | Standard Deviation 0.93 |
| Cohort A: AP-PA02, 3x10^11 PFU/Dose | Post Hoc, Pooled Analysis: P. Aeruginosa Recovery in Sputum Following Multiple Doses of AP-PA02 Administered by Inhalation | 0.1 colony forming units log10 | Standard Deviation 1.17 |