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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Pulmonary Aspergillosis
• Intervention / Treatment: Drug: 12 mg of nebulised 99mTc-liposomal amphotericin B; Drug: 24 mg of nebulised 99mTc-liposomal amphotericin B; Radiation: SPECT/CT scan

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Laura A Michon, MSc; Phone Number: +3124 361 1111; Email: laura.michon@radboudumc.nl

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Radboudumc
    • Contact: Laura A Michon, MSc; Phone Number: +3124 361 1111; Email: laura.michon@radboudumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; First dose 12 mg nebulised AmBisome, second dose 24 mg nebulised AmBisome	Drug: 12 mg of nebulised 99mTc-liposomal amphotericin B; All enrolled subjects will receive nebulised liposomal amphotericin B in addition to standard care. Subjects will be randomly assigned to one of two dosage levels: 12 mg or 24 mg. As this study follows a crossover design, each participant will eventually receive both dosages. Each nebulisation session will have a duration of 10 to 20 minutes, separated by a 14-day washout period between the two sessions; Drug: 24 mg of nebulised 99mTc-liposomal amphotericin B; All enrolled subjects will receive nebulised AmBisome in addition to standard care. Subjects will be randomly assigned to one of two dosage levels: 12 mg or 24 mg. As this study follows a crossover design, each participant will eventually receive both dosages. Each nebulisation session will have a duration of 10 to 20 minutes, separated by a 14-day washout period between the two sessions.; Radiation: SPECT/CT scan; After both nebulisation sessions, a SPECT/CT scan will determine 99mTc-liposomal amphotericin B localization
Experimental: Arm B; First dose 24 mg nebulised AmBisome, second dose 12 mg nebulised AmBisome	Drug: 12 mg of nebulised 99mTc-liposomal amphotericin B; All enrolled subjects will receive nebulised liposomal amphotericin B in addition to standard care. Subjects will be randomly assigned to one of two dosage levels: 12 mg or 24 mg. As this study follows a crossover design, each participant will eventually receive both dosages. Each nebulisation session will have a duration of 10 to 20 minutes, separated by a 14-day washout period between the two sessions; Drug: 24 mg of nebulised 99mTc-liposomal amphotericin B; All enrolled subjects will receive nebulised AmBisome in addition to standard care. Subjects will be randomly assigned to one of two dosage levels: 12 mg or 24 mg. As this study follows a crossover design, each participant will eventually receive both dosages. Each nebulisation session will have a duration of 10 to 20 minutes, separated by a 14-day washout period between the two sessions.; Radiation: SPECT/CT scan; After both nebulisation sessions, a SPECT/CT scan will determine 99mTc-liposomal amphotericin B localization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The amount of AmBisome deposited in the lungs measured through single-photon emission computed tomography (SPECT/CT).	Measured at day 1 (study day 1) and at dat 14 (study day 2) after nebulisation
The amount of AmBisome in the lungs compared to the blood concentrations to understand drug absorption and distribution.	Measured at day 1 (study day 1) and at dat 14 (study day 2) after nebulisation
The most appropriate dose of nebulised AmBisome based on pulmonary deposition and pharmacokinetics	Measured at day 1 (study day 1) and at dat 14 (study day 2) after nebulisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse reactions associated with nebulised AmBisome, including respiratory symptoms, effects on pulmonary function and (S)AEs.		All SAEs and SUSARs occurring within 72 hours after administration of 99mTc-liposomal amphotericin B will be reported
Assessment of patient-reported treatment satisfaction using the Treatment Satisfaction Questionnaire for Medication (TSQM), a validated instrument, to assess side effects, treatment convenience and global satisfaction with therapy.	Patient-reported treatment satisfaction and tolerability of nebulised liposomal amphotericin B will be assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM), version 1.4, a validated patient-reported outcome instrument. The following three TSQM domain scores will be evaluated as part of this outcome measure: Side Effects, Convenience, and Global Satisfaction. Each domain score is transformed to a 0 to 100 scale, with higher scores indicating a better outcome. Specifically, for the Side Effects domain, higher scores indicate fewer or less bothersome side effects; for the Convenience domain, higher scores indicate greater treatment convenience; and for the Global Satisfaction domain, higher scores indicate greater overall satisfaction with therapy. There is no single total TSQM score for this outcome measure; results will be reported separately for each domain.	Measured at day 1 (study visit 1) and at dat 14 (study visit 2) after nebulisation

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: March 23, 2026
• First Submitted That Met QC Criteria: April 9, 2026
• First Posted (Actual): April 15, 2026

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: nebulization; deposition; liposomal amphotericin B; chronic pulmonary aspergillosis; ambisome
• Other Study ID Numbers: R0040621A; 2025-521770-34-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No