Pulmonary aspergillosis MedDRA version: 20.0 Level: LLT Classification code 10059259 Term: Pulmonary aspergillosis System Organ Class: 100000004862
Conditions
Interventions
Product Name: PC945
Pharmaceutical Form: Nebuliser suspension
Current Sponsor code: PC945
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 4.0-
Sponsors
Pulmocide Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject must be male or female, aged 18 years inclusive or older (at the time of consent). 2. Subject must be willing and able to adhere to the restrictions and prohibitions required by this protocol. 3. Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose and requirements of the study and that they are willing to participate. 4. A confirmed diagnosis of CF by standard criteria. 5. Subject is able to produce sputum. 6. A history of persistently positive A. fumigatus sputum cultures from at least 2 sputum samples in the last year, the most recent of which must have been within the last 6 months. 7. Subject must have a positive sputum fungal culture at screening with one or more colonies of A. fumigatus detected using a modified standard approach. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 18 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: 1. Any other disease or condition, which in the Investigator’s medical opinion would preclude the subject’s participation in a clinical trial. 2. Is taking inhaled amphotericin B or has taken it within 7 weeks of Day 1. 3. Is taking systemic steroid treatment or has taken it within 4 weeks of Day 1. Subjects considered to be stable on a systemic steroid dose of 200 mL per episode) within 90 days before screening. 14. Subject is mentally or legally incapacitated. 15. Subject is employed or is a first-degree relative of anyone employed by Pulmocide, a participating clinical trial site, or any contract research organisation involved in the study. 16. Any other reason that the Investigator considers makes the subject unsuitable to participate.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To investigate the safety and tolerability of once daily treatment with inhaled PC945 for 28 days in adult subjects with CF who have persistent pulmonary Aspergillus fumigatus infection • To obtain estimates of derived systemic pharmacokinetic parameters of PC945 and the potential circulating metabolite(s), if detectable, following single and repeat doses of PC945;Secondary Objective: To investigate the effect of PC945 on: - A. fumigatus burden in sputum, measured by the number of CFUs, on fungal culture - The conversion of sputum culture from A. fumigatus +ve to A. fumigatus -ve - A. fumigatus burden in sputum measured by qPCR - A. fumigatus-specific IgG levels - Clinically relevant outcome measures, in particular QoL, cough, breathlessness and sputum characteristic - Markers of A. fumigatus sensitisation: total IgE in subjects with elevated Total IgE levels at study entry, A. fumigatus-specific IgE in subjects with elevated levels of A. fumigatus-specific IgE at study entry To determine if changes in sputum A. fumigatus concentrations on qPCR are related to measures of fungal burden in sputum To investigate correlation between sputum A. fumigatus levels measured by qPCR and clinical variables including CF QoL questionnaire and lung function and to investigate if changes in sputum A. fumigatus measured by qPCR predict clinical response;Primary end point(s): Safety and tolerability parameters: • Adverse events (AEs) • Twelve-lead electrocardiogram (ECG; including QT corrected according to Bazett’s formulae interval, QT interval, QRS Interval, PR Interval and ventricular rate). • Vital signs (systolic and diastolic blood pressure, heart rate and respiratory rate) • Clinical laboratory evaluations (haematology, clinical chemistry, and urinalysis) • Spirometry (FEV1, FVC, MEF25-75 and PEFR) • Visual analogue score (VAS) to assess tolerability (cough, breathlessness) Derived pharmacokinetic parameters for PC945 and the potential circulating meta | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in the number of sputum A. fumigatus CFU from baseline to Visit 3, Visit 4 and at followup (Visit 5) • A. fumigatus status (presence or absence) at Visit 3, Visit 4 and at follow-up Visit 5 in subjects with an A. fumigatus-positive sputum culture at baseline • Change in sputum A. fumigatus measured by qPCR from baseline to Visit 3, Visit 4 and at followup Visit 5 • Change in the serum concentration of A. fumigatus-specific IgG from baseline to Visit 3, Visit 4 and at follow-up Visit 5 • Change in serum Total IgE levels from baseline to Visit 3, Visit 4 and at follow-up Visit 5 • Change in serum Aspergillus-specific IgE levels from baseline to Visit 3, Visit 4 and at follow-up Visit 5 • CFQ-R scores, cough (visual analogue scale), breathlessness (visual analogue scale) and sputum characteristics (e.g. colour, quality) at baseline, Visit 3, Visit 4, and at follow-up at Visit 5 • Correlation between A. fumigatus measured by qPCR and clinical response: e.g., culture, CFQ-R and lung function (FEV1, FVC, MEF25–75 and PEFR) and to investigate if the change in sputum A. fumigatus measured by qPCR predicts clinical response;Timepoint(s) of evaluation of this end point: Sputum: S, D14, 32-36, 84 Blood samples for circulating biomarkers: D1, 14, 32-36, 84 CFQ-R: D1, 14, 32-36, 84 Lung function: S, D1 (PD,0.5 h), D14 (PD, 0.5 h), D32-36, D84 | — |
Countries
United Kingdom
Contacts
Public ContactDirector of Clinical Development
Pulmocide Ltd
Outcome results
None listed