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

• ClinicalTrials.gov Identifier: NCT06016088
• Recruitment Status: Recruiting
• First Posted: August 29, 2023
• Last Update Posted: April 22, 2024
• Sponsor: Respirion Pharmaceuticals Pty Ltd
• Information provided by (Responsible Party): Respirion Pharmaceuticals Pty Ltd

Tracking Information

• First Submitted Date: August 21, 2023
• First Posted Date: August 29, 2023
• Last Update Posted Date: April 22, 2024
• Actual Study Start Date: April 1, 2024
• Estimated Primary Completion Date: April 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 22, 2023)

• Treatment-emergent adverse events [ Time Frame: Day 1 through Day 28 ]
• Treatment-emergent serious adverse events [ Time Frame: Day 1 through Day 28 ]
• Changes in post-dose spirometry [ Time Frame: Day 1, Day 2, and Day 14 ]
  Forced expiratory volume in 1 second
• Pulmonary exacerbations [ Time Frame: Day 1 through Day 28 ]
  A period of treatment with intravenous antibiotics in the hospital and/or at home
• Changes in post-dose electrocardiogram results [ Time Frame: Day 1 and Day 2 ]
  PR interval, QRS interval, QT interval

Original Primary Outcome Measures (submitted: August 24, 2023)

• Treatment-emergent adverse events [ Time Frame: Day 1 through Day 28 ]
• Treatment-emergent serious adverse events [ Time Frame: Day 1 through Day 28 ]
• Changes in post-dose spirometry [ Time Frame: Day 1, Day 2, and Day 14 ]
  forced expiratory volume in 1 second
• Pulmonary exacerbations [ Time Frame: Day 1 through Day 28 ]
  a period of treatment with intravenous antibiotics in the hospital and/or at home
• Changes in post-dose electrocardiogram results [ Time Frame: Day 1 and Day 2 ]
  PR interval, QRS interval, QT interval

Current Secondary Outcome Measures (submitted: December 22, 2023)

• Pharmacokinetic parameters for CaEDTA [ Time Frame: Day 1 ]
• Pharmacokinetic parameters for tobramycin [ Time Frame: Day 1 ]

Original Secondary Outcome Measures (submitted: August 24, 2023)

• Pharmacokinetic parameters for CaEDTA [ Time Frame: Day 1 ]
  Peak serum concentration (Cmax)
• Pharmacokinetic parameters for CaEDTA [ Time Frame: Day 1 through Day 28 ]
  Exposure (area under the serum concentration versus time curve [AUC])
• Pharmacokinetic parameters for CaEDTA [ Time Frame: Day 1 through Day 28 ]
  Time to maximum serum concentration (Tmax)
• Pharmacokinetic parameters for tobramycin [ Time Frame: Day 1 ]
  Peak serum concentration (Cmax)
• Pharmacokinetic parameters for tobramycin [ Time Frame: Day 1 through Day 28 ]
  Exposure (area under the serum concentration versus time curve [AUC])
• Pharmacokinetic parameters for tobramycin [ Time Frame: Day 1 ]
  Time to maximum serum concentration (Tmax)

Current Other Pre-specified Outcome Measures (submitted: December 22, 2023)

• Pharmacodynamic parameters [ Time Frame: Day 1, Day 14, and Day 28 ]
  Biomarkers in sputum
• Microbiology parameters [ Time Frame: Day 1 to Day 14; Day 1 to Day 28 ]
  Change from baseline in Pseudomonas aeruginosa CFUs
• Change from baseline in spirometry [ Time Frame: Day 1 to Day 28 ]
  Forced expiratory volume in 1 second (absolute change; change in % predicted)
• Change from baseline in CFQ-R Respiratory Symptoms Score [ Time Frame: Day 1 to Day 28 ]
• Change from baseline in Chronic Respiratory Infection Symptom Score [ Time Frame: Day 1 to Day 28 ]

Original Other Pre-specified Outcome Measures (submitted: August 24, 2023)

• Pharmacodynamic parameters [ Time Frame: Day 1, Day 14, and Day 28 ]
  Inflammatory markers in sputum
• Microbiology parameters [ Time Frame: Day 1 to Day 14; Day 1 to Day 28 ]
  Change from baseline in Pseudomonas aeruginosa CFUs
• Change from baseline in spirometry [ Time Frame: Day 1 to Day 28 ]
  forced expiratory volume in 1 second (absolute change; change in % predicted)
• Change from baseline in CFQ-R Respiratory Symptoms Score [ Time Frame: Day 1 to Day 28 ]
• Change from baseline in Chronic Respiratory Infection Symptom Score [ Time Frame: Day 1 to Day 28 ]

Descriptive Information

• Brief Title: 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 Study of Aerosolized RSP-1502 Delivered Via the PARI LC Plus® Nebulizer in Subjects With Cystic Fibrosis and Chronic Pseudomonas Aeruginosa Lung Infection
• 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.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Cystic Fibrosis Lung
• Respiratory Infections, Recurrent, Chronic
• Pseudomonas Aeruginosa

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.
• Drug: Tobramycin inhalation solution
  Tobramycin inhalation solution is 300 mg tobramycin in 5 mL solution.

Study Arms

• Experimental: RSP-1502

  Cohorts 1-4 will receive RSP-1502 (300 mg tobramycin plus an ascending dose of CaEDTA).

  Cohort 5 will receive 300 mg tobramycin + CaEDTA at the MTD.

  Intervention: Drug: RSP-1502
• Active Comparator: Active Control
  • Tobramycin Inhalation Solution 300 mg.
  Intervention: Drug: Tobramycin inhalation solution

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 24, 2023): 52
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 2025
• Estimated Primary Completion Date: April 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Brian Jones, PhD; 215-732-5452; bjones@respirionpharma.com

Contact: Sarah Coquillette; scoquillette@respirionpharma.com

• Listed Location Countries: Australia, United States

Administrative Information

• NCT Number: NCT06016088
• Other Study ID Numbers: RESPIR-102
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Respirion Pharmaceuticals Pty Ltd
• Original Responsible Party: Same as current
• Current Study Sponsor: Respirion Pharmaceuticals Pty Ltd
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Respirion Pharmaceuticals Pty Ltd
• Verification Date: April 2024