A Phase 1a/1b Study to Investigate the Safety, Tolerability, Microbiological Response, and Pharmacokinetics of Inhaled Rev-56 in Adult Healthy Volunteers and Adult Non-cystic Fibrosis Bronchiectasis (NCFB) Patients With Chronic P. Aeruginosa

A Sequential, Phase 1a/1b, Double-blind, 2-part Study to Investigate the Safety, Tolerability, Microbiological Response, and Pharmacokinetics of Rev-56 for Inhalation Compared With Placebo in Healthy Adult Participants and Adult Non-cystic Fibrosis Bronchiectasis (NCFB) Patients With Chronic Pseudomonas Aeruginosa

This is a Phase 1a/1b study to test the safety, tolerability, microbiological response, and pharmacokinetics of inhaled Rev-56 compared to placebo in adult healthy participants and non-cystic fibrosis bronchiectasis (NCFB) patients with P. aeruginosa, respectively.

Phase 1a (Part A) will evaluate single doses of inhaled Rev-56 in adult healthy participants and includes up to 5 cohorts. Eligible participants will be randomized to active treatment or placebo in a 3:1 randomization scheme.

Phase 1b (Part B) will evaluate the safety, tolerability, microbiological response, and pharmacokinetics of multiple doses of inhaled Rev-56 in NCFB patients with P. aeruginosa and includes 2 cohorts evaluating once daily dosing and twice daily dosing, respectively. Eligible participants will be randomized to active treatment or placebo in a 2:1 randomization scheme.

Inclusion Criteria (Healthy Participants):

• Healthy male and female participants aged 18 to 55 years, inclusive
• Body mass index > 18 to ≤ 32 kg/m^2
• Forced expiratory volume in 1 second (FEV1) ≥ 80%
• Creatinine clearance ≥ 90 mL/min
• Normal laboratory values and physical exam at screening, or Grade 1 abnormalities that are not clinically significant

Inclusion Criteria (NCFB Patients with P. aeruginosa):

• Male and female NCFB patients aged 18 to 80 years, inclusive
• Bronchiectasis confirmed by prior computerized tomography (CT) scan
• Chronic P. aeruginosa infection (≥ 2 positive cultures within prior 12 months)
• Screening sputum culture positive for P. aeruginosa at ≥ 10^4 CFU/mL
• FEV1 ≥ 50% (post bronchodilator)

Exclusion Criteria (Healthy Participants):

• Clinically significant medical history
• Acute illness within 4 weeks of screening
• Current smoker or nicotine user
• History of alcohol abuse (within prior 12 months) or drug/chemical abuse

Exclusion Criteria (NCFB Patients with P. aeruginosa):

• Primary asthma, chronic obstructive pulmonary disease (COPD), or cystic fibrosis (CF)
• More than 2 pulmonary exacerbations requiring IV antibiotics within 12 months prior to screening
• Receipt of antibiotics (excluding macrolides) within 30 days prior to screening
• Clinically significant hemoptysis requiring intervention within 30 days prior to screening
• Receiving anti-infective treatment for concurrent nontuberculosis mycobacteria (NTM) or fungal infection