The Effect of Early Treatment of PC945 on Aspergillus Fumigatus Lung Infection in Lung Transplant Patients.

Phase 2

Terminated

• Conditions: Lung Transplant Infection; Aspergillosis
• Interventions: Drug: Standard of Care; Drug: PC945

• Registration Number: NCT03905447
• Lead Sponsor: Pulmocide Ltd

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-03-06
• Study First Submitted QC: 2019-04-04
• Study First Posted: 2019-04-05
• Study Start: 2019-09-17
• Status Verified: 2020-06
• Primary Completion: 2020-06-01
• Study Completion: 2020-06-01
• Last Update Submitted: 2021-07-15
• Last Update Posted: 2021-07-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care	Standard of Care	Standard of care anti-fungal medication
PC945	PC945	-

Primary Outcome Measures

Name	Time	Method
Proportion of participants receiving PC945 who meet the markedly abnormal criteria for 12-lead ECG assessment at lease once post dose	Baseline to Week 16
Forced vital capacity (FVC) values from participants receiving PC945	Baseline to Week 16
Proportion of participants receiving PC945 who meet the markedly abnormal criteria for safety laboratory assessment at lease once post dose	Baseline to Week 16
Predicted post bronchodilator forced expiratory volume in 1 second (FEV1) values from participants receiving PC945	Baseline to Week 16
Adverse events (AEs)	48 hours Post Transplant to Week 16 post treatment
Maximum plasma concentration	Baseline to Week 16	Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable
Proportion of participants receiving PC945 who meet the markedly abnormal criteria for vital signs assessment at lease once post dose	Baseline to Week 16
Area under the curve from time 0 to 2 h post-dose (AUC0-2)	Baseline to Week 16	Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable
Concentration at the end of the dosage interval (Ctrough)	Baseline to Week 16	Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable

Secondary Outcome Measures

Name	Time	Method
Lung Concentration of PC945	Baseline to Week 16
A. fumigatus fungal culture status (presence or absence) in subjects with a baseline A. fumigatus-positive bronchoalveolar lavage (BAL)	Baseline to Week 16
Change in BAL A. fumigatus measured by quantitative polymerase chain reaction (qPCR)	Baseline to Week 16
Aspergillus status (Presence or absence) of BAL using an Aspergillus immunochromatographic lateral flow device (AspLFD).	Baseline to Week 16
Subject experience of inhaled amphotericin B	Baseline to Week 16	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.
Change in the number of sputum A. fumigatus colony forming units (CFU) in cultured BAL.	Baseline to Week 16
Galactomannan levels in BAL	Baseline to Week 16
Status of fungal hyphae or pseudohyphae (presence or absence) on cytological examination	Baseline to Week 16
Subject experience of inhaled PC945	Baseline to Week 16	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.

Trial Locations

Locations (3)

Papworth Hospital; 🇬🇧 Papworth Everard, Cambridge, United Kingdom

Wythenshawe Hospital; 🇬🇧 Manchester, United Kingdom

Harefield Hospital; 🇬🇧 Harefield, Uxbridge, United Kingdom