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

NCT06663176 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: RESP30X-001
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-Cystic Fibrosis Bronchiectasis

Keywords

Nitric Oxide

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (7)

• To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.

  58 days

• To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.

  58 days

• To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.

  58 days

• To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.

  58 days

• To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.

  58 days

Study Arms (4)

Part 1-1 (Active)

EXPERIMENTAL

RESP303 Single Ascending Dose Phase followed by Multiple Daily Dosing (28-days)

Drug: RESP303

Part 2-1 (Active)

EXPERIMENTAL

RESP302 TID Single Ascending Dose Phase followed by Multiple Daily Dosing (28-days)

Drug: RESP302

Part 2-2 (Active)

EXPERIMENTAL

RESP303 BID Single Ascending Dose Phase followed by Multiple Daily Dosing (28-days)

Drug: RESP303

Part 2-3 (Active)

EXPERIMENTAL

RESP303 TID Single Ascending Dose Phase followed by Multiple Daily Dosing (28-days)

Drug: RESP303

Interventions

RESP302 DRUG

Nitric Oxide agent

Part 2-1 (Active)

RESP303 DRUG

Nitric Oxide agent

Part 1-1 (Active); Part 2-2 (Active); Part 2-3 (Active)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Thirty Respiratory Limited: lead

Study Sites (1)

ARENSIA Exploratory Medicine

Kyiv, Ukraine

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single Ascending Dose, Multiple Daily Dosing

Study Record Dates

• First Submitted: October 25, 2024
• First Posted: October 29, 2024
• Study Start: October 16, 2024
• Primary Completion (Estimated): February 5, 2028
• Study Completion (Estimated): May 5, 2028
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: Within one year of the end of the trial, data will remain available until the product is withdrawn from the market.

Locations

UA (1)