Nebulised RESP30X Nitric Oxide Formulations in NCFB Patients With Pseudomonas Aeruginosa (Pa) (NOPA)

Phase 1/2a Trial to Evaluate the Safety, Tolerability and Efficacy of Nebulised RESP30X Nitric Oxide Formulations in Non-Cystic Fibrosis Bronchiectasis (NCFB) Patients With Pseudomonas Aeruginosa (Pa) or Other Potentially Pathogenic Micro-organisms (PPMs)

A Phase 1/2a, Multi-Centre, Randomised, Open-label study to assess the safety, tolerability, PK, and efficacy of RESP30X in Adult NCFB participants with confirmed high-titre respiratory PPMs.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Cystic Fibrosis Bronchiectasis
• Intervention / Treatment: Drug: RESP303; Drug: RESP302

Detailed Description

A total of approximately 60 participants will be enrolled in this study, to give 30 participants completing the study.

Part 1: Approximately 12 NCFB patients with confirmed high-titre Pa (≥10^5 CFU/mL) to be enrolled to give 6 participants completing the study.

Participants will receive treatment with nebulised RESP303 in a Single Ascending Dose (SAD) phase followed by RESP303 three times a day (TID) multiple daily dosing for 28-days.

A safety review committee will meet after 6 participants have completed the study to determine whether Part 2 of the study can be initiated.

Part 2: Approximately 48 NCFB patients with confirmed high-titre respiratory PPMs (≥10^5 CFU/mL) to be enrolled to give 24 participants completing the study.

Participants will be randomised to receive treatment with nebulised RESP302 in a SAD phase, followed by RESP302 TID multiple daily dosing for 28-days, or nebulised RESP303 in a SAD phase, followed by either RESP303 twice a day (BID) or RESP303 TID multiple daily dosing for 28-days (1:1:1).

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Ukraine
  • Kyiv, Ukraine
    • ARENSIA Exploratory Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provide written, informed consent prior to all study-related procedures and agree to undergo all study procedures.
• Aged between 18 and 75 years, inclusive.
• Clinical history of bronchiectasis affecting 1 or more lobes based on symptoms (cough, sputum productive and/or recurrent lower respiratory tract infections) as confirmed by historical CT scan and radiology report performed within the last 5 years.
• Confirmed high-titre respiratory PPMs (Part 1: Pa only) at screening ≥10^5 CFU/mL (as determined by central laboratory microbiological cultures).
• Individuals of childbearing potential must agree to use protocol defined method(s) of contraception during the study and for at least 90-days after the last dose of IMP.
• Patients who can produce spontaneous sputum on a daily basis.
• Patients who are able to self-administer the SABA inhaler and study nebuliser for IMP administration effectively in the Investigator's opinion, following training.
• Patients appropriately vaccinated against influenza and pneumococcus at least 14-days prior to Day 1.

Exclusion Criteria:

• Currently receiving therapy with any inhaled antibiotic therapy. Patients who have previously received inhaled antibiotic therapy may be eligible if therapy was discontinued at least 28-days prior to screening.
• Treatment with systemic anti-infective therapy within 28-days prior to screening.
• Participation in other clinical studies with investigational agents within 8 weeks prior to screening.
• Treatment with NO and other NO donor agents, phosphodiesterase inhibitors and lung surfactant drugs, within 30 days prior to screening.
• Treatment with immunosuppressive medications within 2 weeks prior to screening, or systemic corticosteroids, or immunoglobulin therapy for more than 7 days within 2 weeks prior to screening.
• HIV positive AND CD4 < 350 cells/mm3
• FEV1 <55% predicted at the screening visit.
• Significant haemoptysis within 60 days of screening defined as an estimated volume of 50ml at any time.
• History of methaemoglobinaemia.
• Taking medications that may induce methaemoglobinaemia, or have received these within 30 days of screening.
• Baseline SpMet >5%.
• Current smokers of tobacco products, marijuana, e-cigarettes/vaping: a current smoker is defined as having inhaled any of these within 3 months of screening.
• In the opinion of the investigator, patients with an acute exacerbation of NCFB.
• In the opinion of the investigator, any other clinically relevant active respiratory disease with the potential to compromise participant safety or confound interpretation of safety or efficacy outcomes. Patients who have experienced >2 exacerbations of asthma or COPD requiring treatment with systemic corticosteroids within the past 12 months are not eligible.
• Asthma which requires treatment with GINA steps 4-5 suggested medications i.e., high dose ICS and LABA or leukotriene modifier/theophylline for the previous year, or systemic corticosteroids for ≥50% of the previous year to prevent it from becoming "uncontrolled", or which remains "uncontrolled" despite this therapy.
• Patients with a diagnosis of primary ciliary dyskinesia.
• Patients with a diagnosis of pulmonary hypertension.
• Patients with a current diagnosis of TB based on clinical testing or symptoms. Patients with a history of TB who have completed a course or eradication therapy at least 2 years prior to screening may be eligible if there is no clinical suspicion of recurrence. Patients with latent TB are eligible provided they have received adequate treatment per local country guidelines.
• Patients with a diagnosis, or suspected diagnosis, of NTM infection according to the ATS/IDSA statement on diagnosis, treatment, and prevention of non-tuberculous mycobacterial diseases. Patients with a previous positive culture that is suspected to be a contaminant are eligible.
• Symptomatic GERD causing NCFB disease.
• Conditions of increased risk for MetHb formation, significant anaemia or haemoglobinopathy.
• Known allergy to active substance or any excipients, or to auxiliary product.
• Known hypersensitivity to NO.
• History of anaphylaxis to any medication or hospitalisation due to an adverse drug reaction (ADR).
• Patients who are pregnant or breastfeeding.
• Patients planning to conceive a child within the anticipated period of study participation and for at least 90-days after the last dose of IMP in the study.
• Patients unable or unwilling to comply with the protocol or to cooperate fully with the investigator or site personnel.
• Alcohol or drug abuse, that in the opinion of the investigator, is sufficient to compromise the safety or cooperation of the participant.

• Patients with the following toxicities at screening as defined by the enhanced CTCAE toxicity table version 5.0, 27Nov2017.

  1. creatinine >1.5 times upper limit of normal (ULN)
  2. haemoglobin ≤8.0 g/dL
  3. platelets <50x10^9 cells/L
  4. serum potassium <3.5 mmol/L
  5. aspartate aminotransferase (AST) >3 x ULN
  6. alanine aminotransferase (ALT) >3 x ULN
  7. alkaline phosphatase (ALP) ≥ 2.5 x ULN
  8. total bilirubin >1.5 x ULN
  9. total white cell count <2 cells x 10^9/L.
• QTcF >450 milliseconds (males) or 470 milliseconds (females) or history of congenital long QT syndrome, Torsades de Pointes or other clinically significant abnormal ECG at screening or baseline.
• History of solid organ transplantation.
• History of malignancy or treatment for malignancy within the past year.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1-1 (Active); RESP303 Single Ascending Dose Phase followed by Multiple Daily Dosing (28-days)	Drug: RESP303; Nitric Oxide agent
Experimental: Part 2-1 (Active); RESP302 TID Single Ascending Dose Phase followed by Multiple Daily Dosing (28-days)	Drug: RESP302; Nitric Oxide agent
Experimental: Part 2-2 (Active); RESP303 BID Single Ascending Dose Phase followed by Multiple Daily Dosing (28-days)	Drug: RESP303; Nitric Oxide agent
Experimental: Part 2-3 (Active); RESP303 TID Single Ascending Dose Phase followed by Multiple Daily Dosing (28-days)	Drug: RESP303; Nitric Oxide agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, intensity, causality, and seriousness of treatment-emergent adverse events (TEAEs).	A TEAE is defined as any event not present before exposure to the study treatment or any event already present that worsens in either intensity or frequency after exposure to the study treatment. The medical assessment of severity is determined per the CTCAE Toxicity Table Version 5 dated 27 November 2017. (Grade 1-Mild, Grade 2-Moderate, Grade 3-Severe, Grade 4 -Potentially Life threatening, Grade 5-Death) The relationship or association of the study treatment in causing or contributing to the AE will be characterised using the classification and criteria based on Adverse Events Attribution/Casualty Ratings Relatedness Rating table. (Not Related, Unlikely, Possible, Probable, Certain)	58 days
Changes in clinical laboratory values (haematology, clinical chemistry) at each time point.	The following haematological tests will be performed: haemoglobin, MetHb (local laboratory only), haematocrit, mean cell haemoglobin, mean cell volume, red blood cell count, white blood cell count with differentials (neutrophils, lymphocytes, monocytes, eosinophils, and basophils), reticulocyte count, platelet count and rheumatoid factor (Day 1 only). The following serum chemistry tests will be performed: albumin, blood urea nitrogen,creatinine, direct, indirect, and total bilirubin, total protein, ALP, AST, ALT, gamma-glutamyl transferase, creatinine, creatine kinase, lactate dehydrogenase, total cholesterol, calcium, sodium, potassium, chloride glucose and follicle stimulating hormone (FSH) (as required).	58 days
Changes in vital signs (blood pressure, heart rate, temperature, respiratory rate) and SpO2 at each time point.	Vital signs include systolic blood pressure (SBP) and diastolic blood pressure (DBP) (mmHg),heart rate (beats per minute (BPM)), respiratory rate (breaths per minute), SpO2 (%) and body temperature (axillary). On days where there is IMP dosing, vital signs should be performed prior to SABA inhaler administration and before blood draws are taken for safety assessments	58 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.	Plasma PK parameter - Cmax	58 days
To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.	Plasma PK parameter - Tmax	58 days
To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.	Plasma PK parameter - AUC0-t,	58 days
To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.	AUC0-tau	58 days
To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.	Plasma PK parameter - AUC0-inf	58 days
To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.	Plasma PK parameter - Ctrough	58 days
To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.	Plasma PK parameter - t1/2	58 days

Collaborators and Investigators

• Sponsor: Thirty Respiratory Limited

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2024
• Primary Completion (Estimated): February 5, 2028
• Study Completion (Estimated): May 5, 2028

Study Registration Dates

• First Submitted: October 25, 2024
• First Submitted That Met QC Criteria: October 28, 2024
• First Posted (Actual): October 29, 2024

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Nitric Oxide
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Bronchial Diseases; Fibrosis; Bronchiectasis
• Other Study ID Numbers: RESP30X-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Thirty Respiratory confirm that within one year of the end of the trial a summary of data will be uploaded to ClinTrials.gov, and all required data will be available in CTIS within the deadlines specified in relevant EU legislation. This data will remain available until the product is withdrawn from the market. This data will include but is not limited to protocol summary, safety and efficacy data related to the use of the product under the conditions of the clinical trial and which adds to the scientific understanding of the product or class of products. Patient data will be anonymised.
• IPD Sharing Time Frame: Within one year of the end of the trial, data will remain available until the product is withdrawn from the market.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No