Pulmonary Deposition Study of Nebulized Liposomal Amphotericin B and Technetium-99m in Chronic Pulmonary Aspergillosis

The primary objective of the study is to assess the **pulmonary deposition** of liposomal amphotericin B, administered via nebulisation as Technetium-99m labelled AmBisome. This aims to evaluate the intrapulmonary distribution and provide insights to optimize treatment design for patients with chronic pulmonary aspergillosis. Understanding the deposition patterns is clinically relevant as it may enhance the efficacy of inhalation therapy, potentially improving patient outcomes by ensuring targeted delivery of the antifungal agent.

Secondary objectives include:

• Developing, preparing, and validating a GMP-grade procedure for Technetium-99m labelled AmBisome.
• Analyzing the safety and tolerability of nebulised AmBisome.
• Investigating patient-reported outcomes regarding the benefits of inhalation therapy compared to conventional intravenous therapy.

The clinical trial involves participants diagnosed with **chronic pulmonary aspergillosis**. The study population includes both male and female subjects, aged 18 years and older. The trial does not involve a vulnerable population. Participants were selected based on their diagnosis and the absence of significant interference with standard care and follow-up. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits have not been specified in the available data.

The clinical trial is designed to evaluate the **pulmonary deposition** of liposomal **amphotericin B** administered via nebulization as Technetium-99m labeled AmBisome in patients with **chronic pulmonary aspergillosis**. This is a phase III, randomized, double-blind, controlled trial. The trial aims to assess the intrapulmonary distribution and optimize treatment design. The study is expected to commence recruitment on January 5, 2026, and conclude by January 1, 2027. Participants will be involved in the study for a maximum treatment period of two weeks.

The trial includes several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit. During the **screening visit**, eligibility criteria will be confirmed, including age (at least 18 years) and diagnosis of chronic pulmonary aspergillosis. The follow-up visits will involve assessments of the primary endpoints, such as the amount of AmBisome deposited in the lungs measured through single-photon emission computed tomography (SPECT/CT) and comparison of lung and blood concentrations to understand drug absorption and distribution. Secondary endpoints include the development of a validated GMP-grade procedure for Technetium-99m labeled AmBisome and monitoring of adverse reactions, including respiratory symptoms and effects on pulmonary function.

The end-of-study visit will finalize data collection and assess the overall safety and efficacy of the treatment. Participants may be withdrawn from the study if they experience significant adverse events or if there is a protocol violation. The trial will ensure that there is no significant interference with standard care and follow-up for the participants. The study will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.

The clinical trial involves the administration of **AmBisome**, a liposomal formulation of **amphotericin B**, which is a fungistatic and, depending on concentration and susceptibility, fungicidal polyene. The pharmaceutical form of AmBisome is a **dispersion for infusion**, specifically a powder for solution for infusion. The active substance, amphotericin B, is of chemical origin. The maximum daily dose of AmBisome is 24 mg, with a total maximum dose of 36 mg over a treatment period of up to 2 days. The route of administration is via **inhalation**. The product is combined with **Technetium-99m** to facilitate the assessment of pulmonary deposition. The product is not a paediatric formulation and is not classified as an orphan drug.

**Technetium (99mTc) pertechnetate** is used in conjunction with AmBisome in this study. It is provided in the form of a **solution for injection**. The active substance, technetium (99mTc) pertechnetate, is used to label AmBisome, allowing for the evaluation of intrapulmonary distribution. The maximum daily dose for technetium (99mTc) pertechnetate is 55 MBq, with a total maximum dose of 110 MBq over a treatment period of up to 2 days. The administration route is also via inhalation. This product is not a paediatric formulation and does not have orphan drug status.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the measurement of the amount of **AmBisome** deposited in the lungs using single-photon emission computed tomography (SPECT/CT), comparison of lung deposition to blood concentrations to evaluate drug absorption and distribution, and determination of the most appropriate dose of nebulised **AmBisome** based on pulmonary deposition and pharmacokinetics. These assessments will provide insights into the intrapulmonary distribution of the drug and help optimize treatment design.

Secondary endpoints will focus on the development of a validated GMP-grade procedure for Technetium-99m labelled **AmBisome**, monitoring the number of adverse reactions associated with nebulised **AmBisome**, including respiratory symptoms, effects on pulmonary function, and serious adverse events (SAEs). Additionally, patient-reported outcomes (PROs) will be assessed using a validated PRO instrument, the Treatment Satisfaction Questionnaire for Medication (TSQM), to evaluate side effects, treatment convenience, and overall satisfaction with the therapy.