NCT04966234

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

Prospective Validation and Clinical Evaluation of a New Posaconazole Dosing Regimen for Children and Adolescents With Cystic Fibrosis and Aspergillus Infection

• Status: Unknown
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 135 (estimated)
• Sponsor: Bambino Gesù Hospital and Research Institute · Academic / Other
• Sex: All
• Age: 8 Years – 17 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Cystic fibrosis (CF) is the most common inherited life-limiting disease in North European people affecting 90,000 people worldwide with about 45,000 registered in the Patient Registry of the European Cystic Fibrosis Society (ECFS). Progressive lung damage caused by recurrent infection and persistent inflammation is the major determinant of survival with a median age of death at 29 years. Approximately 60% of CF patients are infected with A. fumigatus, a ubiquitous environmental fungus,and its presence is associated with accelerated lung function decline. Half of the patients infected with Aspergillus are \<18 years of age. Evidence to guide clinical management of CF-related Aspergillus disease is lacking. A recent survey showed considerable variability in clinical practice among CF consultants. Two-thirds would treat Aspergillus colonization in patients with CF and two-thirds would use an azole antifungal in addition to steroids in the first line treatment of CF-related allergic bronchopulmonary aspergillosis (ABPA). The results of this survey underscore the limited evidence available to guide management of Aspergillus infection in CF. Posaconazole, being one of the 4 licensed triazole antifungals with good efficacy against Aspergillus species has been chosen as the study drug as it has a better tolerability compared to itraconazole, less toxicity and drug-drug interactions compared to voriconazole and can be administered once daily. Posaconazole is licensed in Europe for the prevention of invasive aspergillus in adult neutropenic patient populations and as salvage therapy for invasive aspergillosis. Several studies have reported on the safety and tolerability of the use of posaconazole in children and adolescents with either haematological malignancies, or chronic granulomatous disease, or those undergoing haematopoietic stem cell transplantation. Currently, no dosing algorithm is available to guide posaconazole dosing in children.

Conditions

• Cystic Fibrosis
• Aspergillosis

Interventions

Type	Name	Description
DRUG	Posaconazole 100 MG [Noxafil]	Posaconazole is a lipophilic, highly permeable triazole, which is practically insoluble in water. Posaconazole inhibits the enzyme CYP51a (also known as Erg11p or lanosterol demethylase). This enzyme is required for catalysation of an essential step in biosynthesis of ergosterol in filamentous fungi and yeasts. Posaconazole is favoured over itraconazole and voriconazole with respect to palatability, tolerability and toxicity profile
DRUG	Posaconazole 40 MG/ML	Posaconazole is a lipophilic, highly permeable triazole, which is practically insoluble in water. Posaconazole inhibits the enzyme CYP51a (also known as Erg11p or lanosterol demethylase). This enzyme is required for catalysation of an essential step in biosynthesis of ergosterol in filamentous fungi and yeasts. Posaconazole is favoured over itraconazole and voriconazole with respect to palatability, tolerability and toxicity profile

Timeline

• Start date: 2021-04-22
• Primary completion: 2023-04-01
• Completion: 2023-11-01
• First posted: 2021-07-19
• Last updated: 2021-07-19

Locations

31 sites across 11 countries: Czechia, France, Germany, Greece, Ireland, Italy, Netherlands, Portugal, Spain, Switzerland, United Kingdom