Deposition of Inhaled Liposomal Amphotericin B in Chronic Pulmonary Aspergillosis (CPA)

Nebulised lIposomal aMphotericin B in Chronic pUlmonary aSpergillosis: a Deposition Study

This study evaluates and aims to optimize inhalation treatment with nebulized liposomal amphotericin B in patients with chronic pulmonary aspergillosis. The primary objective is to assess the pulmonary deposition and intrapulmonary distribution of liposomal amphotericin B after nebulization, using technetium-99m-labeled liposomal amphotericin B and SPECT/CT imaging. The study also aims to generate data to inform optimization of inhalation treatment design.

Participants will receive two different doses of nebulized liposomal amphotericin B (12 mg and 24 mg) on separate study days. After each administration, participants will undergo SPECT/CT imaging to assess pulmonary deposition. Blood samples will be collected on both study days and after study treatment to evaluate safety and measure systemic amphotericin B concentrations. Participants will also perform spirometry using a handheld device and complete a treatment satisfaction questionnaire on both study days.

Prior to participant administration, a Good Manufacturing Practice (GMP)-compliant radiolabelling procedure for technetium-99m-labelled liposomal amphotericin B (99mTc-liposomal amphotericin B) will be developed and validated for clinical use in this study.

Inclusion Criteria:

• The patient is at least 18 years old on the day of inclusion.
• The patients has been diagnosed with chronic pulmonary aspergillosis.
• There is no significant interference with standard care and follow-up.

Exclusion Criteria:

• The patient is breastfeeding, or of childbearing potential and is pregnant, planning to become pregnant within 3 months of the SPECT imaging, unable to provide a negative pregnancy test at screening, or unwilling to use effective contraception during the study and for at least 3 months after the last SPECT scan.
• The patient is not able to lie supine in the scanner.
• The patient has previously reported intolerance to inhalation medication.
• The patient is unable to provide informed consent due to lack of decision-making capacity.