Amendment 1 was written to define post-menopausal status and to increase the number of pregnancy tests performed in subjects taking IP. The number of days that female subjects must use an acceptable effective form of contraception after the final dose of PC945 was increased from 30 days to 55 days to account for the long half-life of PC945. Assessment of subjects’ vital signs were to include temperature recordings. In addition, it was clarified that recognised complications of the lung transplant procedure were not to be recorded as adverse events unless the investigator considered these to be related to the study medication (PC945) or an antifungal prescribed as standard of care.

Amendment 3 included: The criteria for being able to provide Extended PC945 treatment were too stringent (i.e., evidence of Aspergillus fumigatus was required in the Week 6 bronchoscopy for patients to qualify for extended treatment and if these were negative, there was no flexibility to continue treatment). There could be other patients that require >4 weeks of treatment. As cultures may be suppressed by the PC945 in the samples, it was considered to be prudent to also allow continued treatment in those patients that concerned investigators, on clinical grounds (e.g., with clinical or bronchoscopic features of disease). Other changes included : The bronchosorption synthetic absorption matrix (BSAM) sampling for collection of mucosal lining fluid for pharmacokinetic (PK) analysis was removed. Measurement of Aspergillus immunoglobulin (Ig)G, Aspergillus IgE and Total IgE were added. Bacterial microbiome assessments were included. The first in human study data were removed as they were included in the updated Investigator’s Brochure.