Clinical trial NCT06016088: A Double-Blind, Active-Controlled, Multiple-Ascending Dose Study of Aerosolized RSP-1502 in Subjects With CF and Chronic PA Lung Infection
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Cystic Fibrosis Lung
Respiratory Infections, Recurrent, Chronic
Pseudomonas Aeruginosa
Keywords: Pseudomonas aeruginosa
cystic fibrosis
pulmonary infection
tobramycin
lung infection
EDTA
edetate calcium disodium
Lead sponsor: Respirion Pharmaceuticals Pty Ltd
Sponsor class: INDUSTRY
First posted: 2023-08-29
Enrollment: 72
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

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 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, 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.

Primary outcomes:
measure: Treatment-emergent adverse events
timeFrame: Day 1 through Day 28
measure: Treatment-emergent serious adverse events
timeFrame: Day 1 through Day 28
measure: Changes in post-dose spirometry
timeFrame: Day 1, Day 2, and Day 14
measure: Pulmonary exacerbations
timeFrame: Day 1 through Day 28
measure: Changes in post-dose electrocardiogram results
timeFrame: Day 1, Day 2, and Day 14
Secondary outcomes:
measure: Pharmacokinetic parameters for CaEDTA
timeFrame: Day 1, Day 2, Day 14, and Day 28
measure: Pharmacokinetic parameters for tobramycin
timeFrame: Day 1, Day 2, Day 14, and Day 28
Other outcomes:
measure: Pharmacodynamic parameters
timeFrame: Day 1, Day 14, and Day 28
measure: Microbiology parameters
timeFrame: Day 1 to Day 14; Day 1 to Day 28
measure: Change from baseline in spirometry
timeFrame: Day 1 to Day 28
measure: Change from baseline in CFQ-R Respiratory Symptoms Score
timeFrame: Day 1 to Day 28
measure: Change from baseline in Chronic Respiratory Infection Symptom Score
timeFrame: Day 1 to Day 28
Locations:
city: Tucson
country: United States
facility: Tucson Cystic Fibrosis Center
state: Arizona
city: Los Angeles
country: United States
facility: Center for Cystic Fibrosis at Keck Medical Center of USC
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Minneapolis
country: United States
facility: The Minnesota Cystic Fibrosis Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Columbia University Cystic Fibrosis Program
state: New York
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital / University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Austin
country: United States
facility: Dell Children's Medical Center of Central Texas
state: Texas
city: Camperdown
country: Australia
facility: The Alfred Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Nedlands
country: Australia
facility: Lung Institute of Western Australia
state: Western Australia
Study officials:
References: