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

Phase 1RecruitingNCT07709494

Revagenix, Inc.64 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Healthy Participants Non-cystic Fibrosis Bronchiectasis

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Incidence and severity of treatment-emergent adverse events (AEs)

Time frame: 21 days (healthy participants) or 28 days (NCFB patients with P. aeruginosa)

Number of participants with clinically significant abnormalities in lab parameters, vital signs, respiratory function, and ECG parameters graded by FDA Toxicity Grading Scale (for healthy participants) and DAIDS Toxicity Tables (for NCFB patients)

Time frame: 21 days (healthy participants) or 28 days (NCFB patients with P. aeruginosa)

Secondary Outcomes

Maximum observed concentration (Cmax) of Rev-56

Time frame: Healthy Participants: predose, and 5 min, 15 min, 45 min, 90 min, 3h, 6h, 12h, 24h and 48h post inhalation; NCFB Patients: pre-dose, and 5 min, 15 min, 45 min, 90 min, 3h, 8h, 12h (Cohort 2b only) and 24h (Cohort 1b only) after completion of inhalation

Time to Cmax of Rev-56 (Tmax)

Area under the curve from time 0 to last measurable concentration (AUC0-last)

Area under the curve from time 0 to 24 hours after completion of dosing (AUC0-24)

Area under the curve from time 0 to infinity (AUC0-inf)

Clearance of Rev-56 (CL/F)

Half-life of Rev-56 (t½)

Volume of distribution of Rev-56 (Vz/F)

Minimum observed concentration of Rev-56 (Cmin)

Time frame: NCFB Patients: pre-dose, and 5 min, 15 min, 45 min, 90 min, 3h, 8h, 12h (Cohort 2b only) and 24h (Cohort 1b only) after completion of inhalation

Mean P. aeruginosa burden (CFU/mL) in sputum culture compared to baseline

Time frame: 28 days (NCFB patients with P. aeruginosa)