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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
ARENSIA Exploratory Medicine
Kyiv, Ukraine
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)
Time frame: 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).
Time frame: 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
Time frame: 58 days
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.
Plasma PK parameter - Cmax
Time frame: 58 days
To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.
Plasma PK parameter - Tmax
Time frame: 58 days
To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.
Plasma PK parameter - AUC0-t,
Time frame: 58 days
To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.
AUC0-tau
Time frame: 58 days
To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.
Plasma PK parameter - AUC0-inf
Time frame: 58 days
To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.
Plasma PK parameter - Ctrough
Time frame: 58 days
To characterise the PK of RESP30X in NCFB participants with confirmed high-titre respiratory PPMs.
Plasma PK parameter - t1/2
Time frame: 58 days