A New Posaconazole Dosing Regimen for Paediatric Patients With Cystic Fibrosis and Aspergillus Infection

• Status: Recruiting
• Trial end date: 2023-11-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will provide: (1) new insights in the prevalence of Aspergillus infection in children and adolescents with CF aged 8-17 yrs; (2) an in silico modelled dose of posaconazole for children and adolescents with CF and Aspergillus infection aged 8-17 yrs; (3) an intensive sampling PK study to define the optimal dose in a limited number of children and adolescents with CF and Aspergillus infection aged 8-17 yrs; (4) a prospective clinical validation to reduce the residual variability and to allow investigation into PK-PD; and (5) an efficacy evaluation of this dosing regimen to treat Aspergillus infection in children and adolescents with CF to inform future primary efficacy trials.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Bambino Gesù Hospital and Research Institute
• Collaborators: Consorzio per Valutazioni Biologiche e Farmacologiche; Radboud University; University of Exeter
• Treatments: Posaconazole

Criteria

Inclusion Criteria:

1. Diagnosed with cystic fibrosis (genetic diagnosis and/or abnormal sweat test and clinical phenotype of lung disease)

2. Age ≥ 8 yrs and < 18 yrs

3. Body weight ≥20 kg

4. Presence 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 over the previous month

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 [IMP]

Exclusion Criteria:

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