Cystic Fibrosis, Lung Infection, Lung Infection Pseudomonal, Pseudomonas, Pseudomonas Aeruginosa
Conditions
Keywords
phage, bacteriophage, cystic fibrosis, Pseudomonas, Pseudomonas aeruginosa
Brief summary
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
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.
Interventions
BIOLOGICALAP-PA02
Bacteriophage administered via inhalation
OTHERPlacebo
Inactive Placebo administered via inhalation
Sponsors
Cystic Fibrosis Foundation
Armata Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Randomized, double-blind, 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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Day 1 pre-dose through End of Study Visit (28 days post last dose of study drug), up to 4 weeks for single ascending dose and up to 5.5 weeks for multiple ascending dose. | Incidence and severity of treatment emergent adverse events of single and multiple doses of AP-PA02 administered by inhalation |
Countries
United States
Participant flow
Pre-assignment details
Percentages were based on the number of subjects in the Safety Population in each treatment group. The Safety Population included all subjects who were administered at least 1 dose of study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 SAD 3-phage (1x10\^10 PFU single dose) | 3 |
| Cohort 2 SAD 3-phage (3x10\^10 PFU single dose) | 3 |
| Amendment 5 MAD 3-phage (1E10 PFU/dose x 3 doses/day x 3 days) | 2 |
| Cohort 3 MAD 5-phage (5.75x10\^10 PFU/dose x 2 doses/day x 5 days) | 3 |
| Cohort 4 MAD 5-phage (1.5x10\^11 PFU/dose x 2 doses/day x 10 days) | 10 |
| SAD Placebo single dose placebo | 3 |
| MAD Placebo multiple ascending dose placebo | 5 |
| Total | 29 |
Baseline characteristics
| Characteristic | Cohort 1 SAD | Cohort 2 SAD | Amendment 5 MAD | Cohort 3 MAD | Cohort 4 MAD | SAD Placebo | MAD Placebo | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Customized Age at screening | 41.7 years STANDARD_DEVIATION 3.21 | 40.7 years STANDARD_DEVIATION 6.03 | 31.5 years STANDARD_DEVIATION 9.5 | 44.3 years STANDARD_DEVIATION 18.72 | 38.2 years STANDARD_DEVIATION 8.65 | 39.6 years STANDARD_DEVIATION 19.36 | 47.8 years STANDARD_DEVIATION 16.15 | 40.8 years STANDARD_DEVIATION 12.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 10 Participants | 3 Participants | 5 Participants | 29 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 10 Participants | 3 Participants | 4 Participants | 28 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 0 Participants | 2 Participants | 6 Participants | 2 Participants | 1 Participants | 16 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 4 Participants | 1 Participants | 4 Participants | 13 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 | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 2 | 0 / 3 | 0 / 10 | 0 / 3 | 0 / 5 |
| other Total, other adverse events | 1 / 3 | 1 / 3 | 1 / 2 | 0 / 3 | 5 / 10 | 2 / 3 | 4 / 5 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 2 | 0 / 3 | 1 / 10 | 0 / 3 | 0 / 5 |
Outcome results
Primary
Incidence and Severity Treatment Emergent Adverse Events (TEAEs)
Incidence and severity of treatment emergent adverse events of single and multiple doses of AP-PA02 administered by inhalation
Time frame: Day 1 pre-dose through End of Study Visit (28 days post last dose of study drug), up to 4 weeks for single ascending dose and up to 5.5 weeks for multiple ascending dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs | 1 Participants |
| Cohort 1 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any IMP-related TEAEs | 0 Participants |
| Cohort 1 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any IMP-related serious TEAEs | 0 Participants |
| Cohort 1 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 3 (severe) as the worst severity | 0 Participants |
| Cohort 1 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 1 (mild) as the worst severity | 0 Participants |
| Cohort 1 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 5 (death) as the worst severity | 0 Participants |
| Cohort 1 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any serious TEAEs | 0 Participants |
| Cohort 1 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 2 (moderate) as the worst severity | 1 Participants |
| Cohort 1 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 4 (life-threatening) as the worst severity | 0 Participants |
| Cohort 2 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any serious TEAEs | 0 Participants |
| Cohort 2 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 5 (death) as the worst severity | 0 Participants |
| Cohort 2 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any IMP-related TEAEs | 0 Participants |
| Cohort 2 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs | 1 Participants |
| Cohort 2 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 2 (moderate) as the worst severity | 1 Participants |
| Cohort 2 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 4 (life-threatening) as the worst severity | 0 Participants |
| Cohort 2 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any IMP-related serious TEAEs | 0 Participants |
| Cohort 2 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 3 (severe) as the worst severity | 0 Participants |
| Cohort 2 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 1 (mild) as the worst severity | 0 Participants |
| Amendment 5 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 4 (life-threatening) as the worst severity | 0 Participants |
| Amendment 5 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 3 (severe) as the worst severity | 0 Participants |
| Amendment 5 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs | 1 Participants |
| Amendment 5 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any serious TEAEs | 0 Participants |
| Amendment 5 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 2 (moderate) as the worst severity | 1 Participants |
| Amendment 5 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any IMP-related TEAEs | 0 Participants |
| Amendment 5 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any IMP-related serious TEAEs | 0 Participants |
| Amendment 5 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 5 (death) as the worst severity | 0 Participants |
| Amendment 5 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 1 (mild) as the worst severity | 0 Participants |
| Cohort 3 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs | 0 Participants |
| Cohort 3 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any IMP-related serious TEAEs | 0 Participants |
| Cohort 3 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 1 (mild) as the worst severity | 0 Participants |
| Cohort 3 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any serious TEAEs | 0 Participants |
| Cohort 3 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 3 (severe) as the worst severity | 0 Participants |
| Cohort 3 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 2 (moderate) as the worst severity | 0 Participants |
| Cohort 3 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 5 (death) as the worst severity | 0 Participants |
| Cohort 3 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any IMP-related TEAEs | 0 Participants |
| Cohort 3 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 4 (life-threatening) as the worst severity | 0 Participants |
| Cohort 4 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 5 (death) as the worst severity | 0 Participants |
| Cohort 4 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs | 5 Participants |
| Cohort 4 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any serious TEAEs | 1 Participants |
| Cohort 4 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any IMP-related TEAEs | 4 Participants |
| Cohort 4 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any IMP-related serious TEAEs | 0 Participants |
| Cohort 4 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 1 (mild) as the worst severity | 4 Participants |
| Cohort 4 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 2 (moderate) as the worst severity | 0 Participants |
| Cohort 4 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 3 (severe) as the worst severity | 1 Participants |
| Cohort 4 | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 4 (life-threatening) as the worst severity | 0 Participants |
| SAD Placebo | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 2 (moderate) as the worst severity | 1 Participants |
| SAD Placebo | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 1 (mild) as the worst severity | 2 Participants |
| SAD Placebo | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 3 (severe) as the worst severity | 0 Participants |
| SAD Placebo | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any IMP-related serious TEAEs | 0 Participants |
| SAD Placebo | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any serious TEAEs | 0 Participants |
| SAD Placebo | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 5 (death) as the worst severity | 0 Participants |
| SAD Placebo | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 4 (life-threatening) as the worst severity | 0 Participants |
| SAD Placebo | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs | 2 Participants |
| SAD Placebo | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any IMP-related TEAEs | 0 Participants |
| MAD Placebo | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs | 4 Participants |
| MAD Placebo | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 2 (moderate) as the worst severity | 2 Participants |
| MAD Placebo | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any IMP-related serious TEAEs | 0 Participants |
| MAD Placebo | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 5 (death) as the worst severity | 0 Participants |
| MAD Placebo | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 1 (mild) as the worst severity | 2 Participants |
| MAD Placebo | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 3 (severe) as the worst severity | 0 Participants |
| MAD Placebo | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any TEAEs with Grade 4 (life-threatening) as the worst severity | 0 Participants |
| MAD Placebo | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any IMP-related TEAEs | 2 Participants |
| MAD Placebo | Incidence and Severity Treatment Emergent Adverse Events (TEAEs) | Any serious TEAEs | 0 Participants |