Chronic Pulmonary Aspergillosis
Conditions
Keywords
ambisome, liposomal amphotericin B, nebulization, chronic pulmonary aspergillosis, deposition
Brief summary
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.
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.
Interventions
DRUG12 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
DRUG24 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.
RADIATIONSPECT/CT scan
After both nebulisation sessions, a SPECT/CT scan will determine 99mTc-liposomal amphotericin B localization
Sponsors
Radboud University Medical Center
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. | Measured at day 1 (study visit 1) and at dat 14 (study visit 2) after nebulisation | 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. |
Countries
Netherlands
Contacts
CONTACTLaura A Michon, MSc
Outcome results
None listed