A Phase 1b/2a, Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of AP-PA02 Multi-Phage Therapeutic Candidate for Inhalation in Subjects With Cystic Fibrosis and Chronic Pulmonary Pseudomonas Aeruginosa (Pa) Infection
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Cystic Fibrosis
- Sponsor
- Armata Pharmaceuticals, Inc.
- Enrollment
- 29
- Locations
- 20
- Primary Endpoint
- Incidence and Severity Treatment Emergent Adverse Events (TEAEs)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
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
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
Outcomes
Primary Outcomes
Incidence and Severity Treatment Emergent Adverse Events (TEAEs)
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.
Incidence and severity of treatment emergent adverse events of single and multiple doses of AP-PA02 administered by inhalation