Testing aerosolized RSP-1502 for lung infections in cystic fibrosis patients

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

This study is testing if a new inhaled treatment called RSP-1502 can help people with cystic fibrosis who have lung infections caused by a specific bacteria.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 72 (estimated)
• Ages: 12 Years and up
• Sex: All
• Sponsor: Respirion Pharmaceuticals Pty Ltd (Industry-sponsored)
• Drugs / interventions: prednisone
• Locations: 22 sites (Tucson, Arizona and 21 other locations)
• Trial ID: NCT06016088 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of aerosolized RSP-1502 in patients with cystic fibrosis who have chronic lung infections caused by Pseudomonas aeruginosa. The study employs a double-blind, active-controlled, multiple-ascending dose design, where participants will receive varying doses of RSP-1502 or an active control via inhalation over a 14-day period. Following the determination of the maximum tolerated dose (MTD), a dose expansion cohort will continue with the MTD treatment. Participants will be monitored for an additional 14 days after completing the dosing regimen.

Who should consider this trial

Good fit: Ideal candidates include males and females aged 12 years and older with a confirmed diagnosis of cystic fibrosis and a history of Pseudomonas aeruginosa lung infections.

Not a fit: Patients with significant acute respiratory symptoms or those unable to withhold other inhaled antibiotics during the study may not benefit from this trial.

Why it matters

Potential benefit: If successful, this treatment could significantly improve lung function and reduce chronic infections in cystic fibrosis patients.

How similar studies have performed: Previous studies have shown promise with similar aerosolized treatments for lung infections in cystic fibrosis, suggesting potential for success in this approach.

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.

Where this trial is running

Tucson, Arizona and 21 other locations

• Tucson Cystic Fibrosis Center — Tucson, Arizona, United States (Recruiting)
• Center for Cystic Fibrosis at Keck Medical Center of USC — Los Angeles, California, United States (Recruiting)
• Stanford University Medical Center — Palo Alto, California, United States (Recruiting)
• Augusta University — Augusta, Georgia, United States (Recruiting)
• The Cystic Fibrosis Institute — Northfield, Illinois, United States (Recruiting)
• Tulane University — New Orleans, Louisiana, United States (Recruiting)
• The Minnesota Cystic Fibrosis Center — Minneapolis, Minnesota, United States (Recruiting)
• Washington University School of Medicine — St Louis, Missouri, United States (Recruiting)
• Columbia University Cystic Fibrosis Program — New York, New York, United States (Recruiting)
• Rainbow Babies and Children's Hospital / University Hospitals Cleveland Medical Center — Cleveland, Ohio, United States (Recruiting)
• Nationwide Children's Hospital — Columbus, Ohio, United States (Recruiting)
• University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)
• Dell Children's Medical Center of Central Texas — Austin, Texas, United States (Recruiting)
• Royal Prince Albert Hospital — Camperdown, New South Wales, Australia (Recruiting)
• Westmead Hospital — Westmead, New South Wales, Australia (Recruiting)
• Queensland Children's Hospital — Brisbane, Queensland, Australia (Recruiting)
• The Prince Charles Hospital — Brisbane, Queensland, Australia (Recruiting)
• Royal Adelaide Hospital — Adelaide, South Australia, Australia (Recruiting)
• The Alfred Hospital — Melbourne, Victoria, Australia (Recruiting)
• The Royal Children's Hospital — Parkville, Victoria, Australia (Recruiting)
• Lung Institute of Western Australia — Nedlands, Western Australia, Australia (Recruiting)
• The Kids Research Institute Australia, Perth Children's Hospital — Perth, Western Australia, Australia (Recruiting)

Study contacts

• Study coordinator: Brian Jones, PhD

Conditions Cystic Fibrosis Lung; Respiratory Infections, Recurrent, Chronic; Pseudomonas Aeruginosa; Pseudomonas aeruginosa; cystic fibrosis; pulmonary infection; tobramycin; lung infection