A Double-Blind, Active-Controlled, Multiple-Ascending Dose Study of Aerosolized RSP-1502 in Subjects With CF and Chronic PA Lung Infection

Inclusion Criteria:

• Males or females aged ≥18 years of age for cohorts 1-4; males or females ≥12 yearsof age for cohort 5.

• Diagnosis of CF based on the following: historical positive sweat chloride value ≥ 60 mEq/L, and/or genotype with two identifiable mutations consistent with CF,accompanied by one or more clinical features consistent with the CF phenotype.

• History of P. aeruginosa-positive sputum cultures or throat swabs with at least 50%positive in the year preceding screening.

• P. aeruginosa-positive sputum culture at screening.

• Forced expiratory volume in 1 second (FEV1) ≥ 40 and ≤ 90% predicted per Global LungFunction Initiative (GLI) equation, pre- or post-bronchodilator.

• Must be able to withhold all other inhaled tobramycin from Day -28 to Day 28 ofstudy participation. Must be able to withhold all other inhaled antibiotics from Day -14 to Day 28.

• Medically stable with no evidence of significant new or acute respiratory symptomswithin 30 days prior to screening.

• Hematology, clinical chemistry, and urinalysis results with no clinicallysignificant abnormalities that would interfere with the study assessments atscreening as determined by the investigator.

• Female subjects of childbearing potential, defined as not surgically sterile or atleast 2 years postmenopausal, must agree to use one of the following forms ofcontraception from screening through the Day 28 visit: hormonal (oral, implant, orinjection) begun > 30 days prior to screening, barrier (condom, diaphragm withspermicide), intrauterine device, or vasectomized partner (6 months minimum).

• Male subjects must show documentation of infertility or agree to use condoms duringstudy participation.

• Must be able to communicate with site personnel and to understand and voluntarilysign the Informed Consent Form, and be capable and willing to complete all studyvisits and perform all study required procedures.

Exclusion Criteria:

• A history of previous allergy or sensitivity to components of RSP 1502.

• A history of intolerance to inhaled tobramycin (TOBI®, BETHKIS®, TOBI® Podhaler®,tobramycin inhalation solution).

• eGFR < 40 mL/min, or serum total bilirubin > 2X or serum transaminases > 3X theupper limit of normal range at screening.

• Currently taking other medications with known nephrotoxic, neurotoxic, or ototoxicpotential (subjects receiving inhaled tobramycin in conjunction with low doseazithromycin prior to study participation without evidence of ototoxicity maycontinue taking low dose azithromycin during the study).

• Currently taking ethacrynic acid, furosemide, urea, or intravenous mannitol.

• Lung infection with organisms associated with a more rapid decline in pulmonarystatus (including, but not limited to, Burkholderia cenocepacia, Burkholderiadolosa, and Mycobacterium abscessus). For subjects who have had a history of apositive culture, the investigator will apply the following criteria to establishwhether the subject is free of infection with such organisms:

1. The subject has not had a respiratory tract culture positive for theseorganisms within the 12 months before the date of informed consent.

2. The subject has had at least 2 respiratory tract cultures negative for suchorganisms within the 12 months before the date of informed consent, with thefirst and last of these separated by at least 3 months, and the most recent onewithin the 6 months before the date of informed consent.

• Consistent inability to produce sputum and unwillingness to perform sputuminduction.

• Any acute upper or lower respiratory tract infection or pulmonary exacerbationrequiring changes in therapy (including systemic antibiotics), or other significantclinical/laboratory/radiological/spirometric sign of unstable or unexpectedlydeteriorating respiratory disease within 30 days prior to the first study drugadministration.

• Initiation or adjustment of chronic airway medications (eg, inhaled corticosteroids;chronic suppressive antibacterial treatment) or airway clearance regimen (eg,nebulized saline, rhDNase, initiation of mechanical vest or handheld airwayclearance device) within 28 days prior to screening. Individuals can be rescreened 28 days after these agents/therapies have been established for at least 28 days.

• Is immunocompromised due to illness, or solid or hematological organ transplant.

• Requires systemic prednisone (or equivalent) > 10 mg daily.

• Vaping or smoking tobacco or any other substance within 1 month prior to screeningand anticipated inability to refrain from vaping or smoking throughout the study.

• Female subjects who are pregnant, lactating, or have a positive urine humanchorionic gonadotropin (pregnancy) test, as determined by laboratory testing.

• HIV positive.

• Active Hepatitis B or C.

• History of recreational drug or alcohol use/abuse which in the opinion of theinvestigator will compromise the patient's ability to comply with the studyprotocol.

• Participation in a clinical study with administration of an investigational drugproduct within the previous 30 days, or five half-lives of the previouslyadministered investigational product.

• Has any other medical condition(s) which, in the opinion of the PrincipalInvestigator, would jeopardize the safety of the study subject or impact thevalidity of the study results.