This study tests the effects of pre-emptive treatment with an experimental drug PC945 in lung transplant recipients whose lungs are infected by the fungus Aspergillus fumigatus. PC945 may be useful in treating patients infected with Aspergillus fumigatus as, unlike the usual treatments, it is inhaled into the lung and has been designed to stay there and treat the infection. Participants will be monitored for up-to 12 weeks for the presence of Aspergillus in their lungs. Suitable participants will receive PC945 for an initial 28 days (Pre-emptive treatment phase) and, if needed, a further 8-weeks (Extended treatment phase).The amount of fungus in the patients' lungs will be measured over the course of the study. Participants with lung infections but not eligible for PC945 will be followed-up for 16-weeks on standard of care treatment. The study will take place at multiple sites in UK and 10 participants will receive PC945. The maximum study duration will be about 28 weeks.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
2
Nebulized PC945 5mg OD for 28 days with an optional extended treatment period of a further 56 days.
Standard of Care antifungal medication
Papworth Hospital
Papworth Everard, Cambridge, United Kingdom
Harefield Hospital
Harefield, Uxbridge, United Kingdom
Wythenshawe Hospital
Manchester, United Kingdom
Adverse events (AEs)
Time frame: 48 hours Post Transplant to Week 16 post treatment
Proportion of participants receiving PC945 who meet the markedly abnormal criteria for 12-lead ECG assessment at lease once post dose
Time frame: Baseline to Week 16
Proportion of participants receiving PC945 who meet the markedly abnormal criteria for vital signs assessment at lease once post dose
Time frame: Baseline to Week 16
Proportion of participants receiving PC945 who meet the markedly abnormal criteria for safety laboratory assessment at lease once post dose
Time frame: Baseline to Week 16
Predicted post bronchodilator forced expiratory volume in 1 second (FEV1) values from participants receiving PC945
Time frame: Baseline to Week 16
Forced vital capacity (FVC) values from participants receiving PC945
Time frame: Baseline to Week 16
Area under the curve from time 0 to 2 h post-dose (AUC0-2)
Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable
Time frame: Baseline to Week 16
Maximum plasma concentration
Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable
Time frame: Baseline to Week 16
Concentration at the end of the dosage interval (Ctrough)
Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable
Time frame: Baseline to Week 16
Lung Concentration of PC945
Time frame: Baseline to Week 16
A. fumigatus fungal culture status (presence or absence) in subjects with a baseline A. fumigatus-positive bronchoalveolar lavage (BAL)
Time frame: Baseline to Week 16
Change in BAL A. fumigatus measured by quantitative polymerase chain reaction (qPCR)
Time frame: Baseline to Week 16
Change in the number of sputum A. fumigatus colony forming units (CFU) in cultured BAL.
Time frame: Baseline to Week 16
Galactomannan levels in BAL
Time frame: Baseline to Week 16
Aspergillus status (Presence or absence) of BAL using an Aspergillus immunochromatographic lateral flow device (AspLFD).
Time frame: Baseline to Week 16
Status of fungal hyphae or pseudohyphae (presence or absence) on cytological examination
Time frame: Baseline to Week 16
Subject experience of inhaled PC945
Assessed by a standardised study-specific questionnaire assessing participants' subjective experience across a number of domains including taste, smell and overall acceptability following inhalation of PC945.
Time frame: Baseline to Week 16
Subject experience of inhaled amphotericin B
Assessed by a standardised study-specific questionnaire assessing participants' subjective experience across a number of domains including taste, smell and overall acceptability, following inhalation of amphotericin B.
Time frame: Baseline to Week 16
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.