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

An Open-label, Pilot Study to Assess Safety, Tolerability, Pharmacokinetics and Effects of Inhaled PC945 in the Pre-emptive Treatment of Aspergillus Fumigatus Colonisation in Lung Transplant Recipients

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.

Inclusion Criteria (Surveillance Phase)

• Between the ages of 18 and 85 years.
• Received a single or bilateral lung transplant.
• Provided written informed consent prior to transplant

Exclusion Criteria (Surveillance Phase)

• Is precluded from participating in this study as a result of treatment with another investigational drug or participation in another clinical trial.
• If female, the subject is pregnant, lactating or breast feeding.
• Any other clinically significant disease or condition, which in the Investigator's medical opinion would preclude the subject's participation in a clinical trial (e.g., recent myocardial infarction).
• 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.
• Is receiving antiretroviral protease inhibitor therapy.
• Has human immunodeficiency virus or chronic, active hepatitis infection, or had a positive hepatitis B surface antigen or hepatitis C virus RNA test prior to transplant.
• Any known history or current evidence of alcohol or drug abuse that, in the Investigator's opinion, would exclude the subject from participation in the study

Inclusion Criteria (Pre-emptive Treatment Phase)

• A positive test for A. fumigatus in BAL during the Surveillance Phase of the study
• Provided written informed consent for participating in the Pre-Emptive Treatment Phase.

Exclusion Criteria (Pre-emptive Treatment Phase)

• Clinical, endobronchial and/or radiological features of fungal disease.*
• Any other disease or condition, which in the Investigator's medical opinion would preclude the subject's participation in the Pre-Emptive Treatment Phase of the study (e.g., recent myocardial infarction).

Inclusion Criteria (Follow-up Phase - SOC Antifungal Treatment)

• Subject is not eligible to receive pre-emptive PC945 treatment due to either clinical, endobronchial and/or radiological features of fungal disease OR a fungal infection other than A. fumigatus in BAL, that requires SoC antifungal treatment to be started during the Surveillance Phase of the study.
• Provided written informed consent for participating in the Follow-Up Phase for SoC antifungal treatment.

Exclusion Criteria (Follow-up Phase - SOC Antifungal Treatment)

• Any other disease or condition, which in the Investigator's medical opinion would preclude the subject's participation in the Follow-Up Phase for SoC antifungal treatment.