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

NCT06016088 · Respirion Pharmaceuticals Pty Ltd
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Official title
A Double-Blind, Active-Controlled, Multiple-Ascending Dose, Phase 1b/2a Study of Aerosolized RSP-1502 Delivered Via the PARI LC Plus® Nebulizer in Subjects With Cystic Fibrosis and Chronic Pseudomonas Aeruginosa Lung Infection
About this study
This dose escalation safety study will evaluate several doses of RSP-1502 or active control administered by inhalation for 14 days. Following determination of the MTD, a dose expansion cohort will receive RSP-1502 at the MTD versus active control administered by inhalation for 14 days. All subjects will be followed for 14 days after completion of dosing.
Eligibility criteria
Inclusion Criteria: * Males or females aged ≥18 years of age for cohorts 1-4; males or females ≥12 years of 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 2 years preceding screening. * P. aeruginosa-positive sputum culture at screening. * Forced expiratory volume in 1 second (FEV1) ≥ 30 and ≤ 120% 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, and be capable and willing to complete all study visits 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 the upper limit of normal range at screening. * Currently taking other medications with known nephrotoxic, neurotoxic, or ototoxic potential (subjects receiving inhaled tobramycin in conjunction with low dose azithromycin prior to study participation without evidence of ototoxicity may continue 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 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 acute upper or lower respiratory tract infection or pulmonary exacerbation requiring changes in therapy (including systemic antibiotics), or other 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. * Vaping or smoking tobacco or any other substance within 1 month prior to screening and anticipated inability to refrain from vaping or smoking throughout the study. * Female subjects who are pregnant, lactating, or have a positive urine 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. * Has any other medical condition(s) which, in the opinion of the Principal Investigator, would jeopardize the safety of the study subject or impact the validity of the study results.
Study design
Enrollment target: 72 participants
Allocation: randomized
Masking: quadruple
Age groups: child, adult, older_adult
Timeline
Starts: 2024-04-01
Estimated completion: 2026-06
Last updated: 2025-12-29
Interventions
Drug: RSP-1502Drug: Tobramycin inhalation solution
Primary outcomes
  • Treatment-emergent adverse events (Day 1 through Day 28)
  • Treatment-emergent serious adverse events (Day 1 through Day 28)
  • Changes in post-dose spirometry (Day 1, Day 2, and Day 14)
Sponsor
Respirion Pharmaceuticals Pty Ltd · industry
Contacts & investigators
ContactBrian Jones, PhD · contact · bjones@respirionpharma.com · 215-732-5452
ContactSarah Coquillette · contact · scoquillette@respirionpharma.com
All locations (22)
Tucson Cystic Fibrosis CenterRecruiting
Tucson, Arizona, United States
Center for Cystic Fibrosis at Keck Medical Center of USCRecruiting
Los Angeles, California, United States
Stanford University Medical CenterRecruiting
Palo Alto, California, United States
Augusta UniversityRecruiting
Augusta, Georgia, United States
The Cystic Fibrosis InstituteRecruiting
Northfield, Illinois, United States
Tulane UniversityRecruiting
New Orleans, Louisiana, United States
The Minnesota Cystic Fibrosis CenterRecruiting
Minneapolis, Minnesota, United States
Washington University School of MedicineRecruiting
St Louis, Missouri, United States
Columbia University Cystic Fibrosis ProgramRecruiting
New York, New York, United States
Rainbow Babies and Children's Hospital / University Hospitals Cleveland Medical CenterRecruiting
Cleveland, Ohio, United States
Nationwide Children's HospitalRecruiting
Columbus, Ohio, United States
University of PennsylvaniaRecruiting
Philadelphia, Pennsylvania, United States
Dell Children's Medical Center of Central TexasRecruiting
Austin, Texas, United States
Royal Prince Albert HospitalRecruiting
Camperdown, New South Wales, Australia
Westmead HospitalRecruiting
Westmead, New South Wales, Australia
Queensland Children's HospitalRecruiting
Brisbane, Queensland, Australia
The Prince Charles HospitalRecruiting
Brisbane, Queensland, Australia
Royal Adelaide HospitalRecruiting
Adelaide, South Australia, Australia
The Alfred HospitalRecruiting
Melbourne, Victoria, Australia
The Royal Children's HospitalRecruiting
Parkville, Victoria, Australia
Lung Institute of Western AustraliaRecruiting
Nedlands, Western Australia, Australia
The Kids Research Institute Australia, Perth Children's HospitalRecruiting
Perth, Western Australia, Australia
A Double-Blind, Active-Controlled, Multiple-Ascending Dose Study of Aerosolized RSP-1502 in Subjects With CF and Chronic PA Lung Infection · TrialPath