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

Pseudomonas Aeruginosa Clinical Trial

Official title:

A Double-Blind, Active-Controlled, Multiple-Ascending Dose, Phase 1b Study of Aerosolized RSP-1502 Delivered Via the PARI LC Plus® Nebulizer in Subjects With Cystic Fibrosis and Chronic Pseudomonas Aeruginosa Lung Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06016088
• Other study ID #: RESPIR-102
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 1, 2024
• Est. completion date: April 2025

Study information

• Verified date: May 2024
• Source: Respirion Pharmaceuticals Pty Ltd
• Contact: Brian Jones, PhD
• Phone: 215-732-5452
• Email: bjones[@]respirionpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 52
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Cystic Fibrosis
• Cystic Fibrosis Lung
• Fibrosis
• Infections
• Pseudomonas Aeruginosa
• Pseudomonas Infections
• Pulmonary Fibrosis
• Respiratory Tract Infections

Intervention

Drug:
• RSP-1502
RSP-1502 is a sterile, preservative free solution to be administered by inhalation via a nebulizer. Each dose of RSP-1502 contains the active components tobramycin (300 mg) and CaEDTA in a 5 mL solution.
• Tobramycin inhalation solution
Tobramycin inhalation solution is 300 mg tobramycin in 5 mL solution.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	The Alfred Hospital	Camperdown	New South Wales
Australia	Lung Institute of Western Australia	Nedlands	Western Australia
Australia	Westmead Hospital	Westmead	New South Wales
United States	Augusta University	Augusta	Georgia
United States	Dell Children's Medical Center of Central Texas	Austin	Texas
United States	Rainbow Babies and Children's Hospital / University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Center for Cystic Fibrosis at Keck Medical Center of USC	Los Angeles	California
United States	The Minnesota Cystic Fibrosis Center	Minneapolis	Minnesota
United States	Tulane University	New Orleans	Louisiana
United States	Columbia University Cystic Fibrosis Program	New York	New York
United States	Stanford University Medical Center	Palo Alto	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Tucson Cystic Fibrosis Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Respirion Pharmaceuticals Pty Ltd

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacodynamic parameters	Biomarkers in sputum	Day 1, Day 14, and Day 28
Other	Microbiology parameters	Change from baseline in Pseudomonas aeruginosa CFUs	Day 1 to Day 14; Day 1 to Day 28
Other	Change from baseline in spirometry	Forced expiratory volume in 1 second (absolute change; change in % predicted)	Day 1 to Day 28
Other	Change from baseline in CFQ-R Respiratory Symptoms Score		Day 1 to Day 28
Other	Change from baseline in Chronic Respiratory Infection Symptom Score		Day 1 to Day 28
Primary	Treatment-emergent adverse events		Day 1 through Day 28
Primary	Treatment-emergent serious adverse events		Day 1 through Day 28
Primary	Changes in post-dose spirometry	Forced expiratory volume in 1 second	Day 1, Day 2, and Day 14
Primary	Pulmonary exacerbations	A period of treatment with intravenous antibiotics in the hospital and/or at home	Day 1 through Day 28
Primary	Changes in post-dose electrocardiogram results	PR interval, QRS interval, QT interval	Day 1 and Day 2
Secondary	Pharmacokinetic parameters for CaEDTA		Day 1
Secondary	Pharmacokinetic parameters for tobramycin		Day 1