Prospective validation and clinical evaluation of a new posaconazole dosing regimen for children and adolescents with cystic fibrosis and Aspergillus infectio

Phase 2

Withdrawn

• Conditions: 10038686; 10017528; 10006436; Aspergillus infection; cystic fibrosis

• Registration Number: NL-OMON54920
• Lead Sponsor: IRCCS Ospendale Pediatrico Bambino Gesu

Brief Summary

Trial never started

Detailed Description

Not available

Study Timeline

• Results First Posted: 2022-07-21
• Last Update Posted: 9 April 2024

Recruitment & Eligibility

• Status: Withdrawn
• Sex: Not specified
• Target Recruitment: 18

Inclusion Criteria

135 children and adolescents will be included. We strive to include 45 children
each in the following weight bands: 20-30 kg; 30-40 kg; >40 kg body weight
Inclusion criteria for the screening phase of the study (n<=1500):
Subjects must meet the following criteria to be eligible for participation in
the screening phase:
1. Diagnosed with CF (genetic diagnosis and/or abnormal sweat test and clinical
phenotype of lung disease).
2. Age * 8 yrs and < 18 yrs.
3. Able to produce sputum sample (spontaneous or induced sputum).
4. Informed Consent given.

Inclusion criteria for the posaconazole trial
1. Diagnosed with CF (genetic diagnosis and clinical phenotype of lung disease).
2. Age * 8 yrs and < 18 yrs.
3. Body weight *20 kg
4. Signs of Aspergillus infection as defined for this study.
5. Clinically stable condition without a significant change in lung function
(FEV1 +/- 10%) or significant worsening of respiratory symptoms in the month
preceding signing of the ICF
6. Able to perform lung function test (FEV1%).
7. Able to produce a sputum sample (spontaneous or induced sputum)
8. Informed Consent given.
9. If female and of childbearing age must be using highly effective
contraception (and must agree to continue for 7 days after the last dose of
investigational medicinal product

Exclusion Criteria

Exclusion criteria for the screening phase of the study (n=1500):
1. Non-CF lung disorder
2. Age < 8 yrs of age or * 18 yrs of age
3. Body weight <20 kg
4. Not able to provide sputum sample
5. Informed Consent not given

Exclusion criteria for the posaconazole trial (n=135)
1. Non-CF lung disorder
2. Age < 8 yrs or * 18 yrs
3. Body weight < 20 kg
4. Not able to perform lung function test (FEV1%)
5. Unable to produce a sputum sample (spontaneous or induced sputum)
6. Clinically unstable condition with significant change in lung function or
significant worsening of respiratory symptoms
7. Unable to tolerate oral medication
8. Known hypersensitivity to itraconazole or posaconazole, or it*s excipients.
9. On active transplant list or transplant recipient
10. Azole resistant Aspergillus sp. cultured
11. Patients receiving terfenadine, ergot alkaloids, astemizole, cisapride,
pimozide, halofantrine, quinidine, or HMG-CoA reductase inhibitors metabolised
through CYP3A4 (eg. simvastatin, lovastatin, and atorvastatin)
12. Patients receiving omalizumab
13. Received systemic mould-active antifungals in the last month
14. Shortened or elongated QT interval
15. Cardiac failure
16. ALT * 200 U/L
17. AST * 225 U/L
18. Alkaline phosphatase * 460 U/L
19. Bilirubin * 50 umol/L
20. eGFR < 20 ml/min/1.73 m2 (calculated with the Schwartz formula
21. Patients with known glucose-galactose malabsorption problems
22. Pregnancy2 or breastfeeding
23. Females of childbearing age who do not intend to use contraception measures.
24. Informed Consent not given

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>In view of the dual objectives for this trial, which is reflected in the<br /><br>design, there are two primary endpoints.<br /><br>Primary endpoints:<br /><br>-For validation of the dosing algorithm: The number of children and adolescents<br /><br>with CF and Aspergillus infection aged 8 to 17 years reaching the pre-defined<br /><br>area under the concentration time curve (AUC) of posaconazole at the first<br /><br>assessment (between day 5 and 10) based on the adult reference concentrations<br /><br>for treatment of susceptible pathogens.<br /><br>-For clinical efficacy: The number of children with negative sputum sample for<br /><br>Aspergillus infection at 3 months.</p><br>