Overview

A double-blind, active-controlled, multiple-ascending dose, safety study of aerosolized RSP-1502 in subjects with cystic fibrosis Pseudomonas aeruginosa lung infection.

Eligibility

Inclusion Criteria:

• Males or females aged ≥18 years of age.
• 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 Lung Function Initiative (GLI) equation, pre- or post-bronchodilator.
• Must be able to withhold all other inhaled tobramycin from Day 28 to Day 28 of study 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 symptoms within 30 days prior to screening.
• Hematology, clinical chemistry, and urinalysis results with no clinically significant abnormalities that would interfere with the study assessments at screening as determined by the investigator.
• Female subjects of childbearing potential, defined as not surgically sterile or at least 2 years postmenopausal, must agree to use one of the following forms of contraception from screening through the Day 28 visit: hormonal (oral, implant, or injection) begun > 30 days prior to screening, barrier (condom, diaphragm with spermicide), intrauterine device, or vasectomized partner (6 months minimum).
• Male subjects must show documentation of infertility or agree to use condoms during study participation.
• Must be able to communicate with site personnel and to understand and voluntarily sign the Informed Consent Form.

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 bilirubin > 2X or serum transaminases > 3X the upper limit of normal range at screening.
• Currently taking other medications with known nephrotoxic, neurotoxic, or ototoxic potential.
• Currently taking ethacrynic acid, furosemide, urea, or intravenous mannitol.
• Lung infection with organisms associated with a more rapid decline in pulmonary status (including, but not limited to, Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus). For subjects who have had a history of a positive culture, the investigator will apply the following criteria to establish whether the subject is free of infection with such organisms:
  1. The subject has not had a respiratory tract culture positive for these organisms within the 12 months before the date of informed consent.
  2. The subject has had at least 2 respiratory tract cultures negative for such organisms within the 12 months before the date of informed consent, with the first and last of these separated by at least 3 months, and the most recent one within the 6 months before the date of informed consent.
• Consistent inability to produce sputum and unwillingness to perform sputum induction.
• Any significant clinical/laboratory/radiological/spirometric sign of unstable or unexpectedly deteriorating respiratory disease within 30 days prior to the first study drug administration.
• 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 airway clearance 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.
• Smoking or vaping tobacco or any substance within 6 months prior to screening and anticipated inability to refrain from smoking throughout the study.
• Female subjects who are pregnant, lactating, or have a positive serum human chorionic 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 the investigator will compromise the patient's ability to comply with the study protocol.
• Participation in a clinical study with administration of an investigational drug product within the previous 30 days, or five half-lives of the previously administered investigational product.