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

Last updated: July 7, 2021
Sponsor: Bambino Gesù Hospital and Research Institute
Overall Status: Active - Recruiting

Phase

2/3

Condition

Cystic Fibrosis

Scar Tissue

Aspergillosis

Treatment

N/A

Clinical Study ID

NCT04966234
cASPerCF_2007_OPBG_2019
2019-004511-31
  • Ages 8-17
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Diagnosed with cystic fibrosis (genetic diagnosis and/or abnormal sweat test andclinical 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 (andmust agree to continue for 7 days after the last dose of investigational medicinalproduct [IMP]

Exclusion

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 significantworsening 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

Total Participants: 135
Study Start date:
April 22, 2021
Estimated Completion Date:
November 30, 2023

Study 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.

Connect with a study center

  • Motol University Hospital

    Prague,
    Czechia

    Site Not Available

  • Centre hospitalier universitaire Dijon Bourgogne

    Bourgogne,
    France

    Site Not Available

  • Centre hospitalier universitaire Grenoble Alpes

    Grenoble,
    France

    Site Not Available

  • Centre hospitalier universitaire de Montpellier

    Montpellier,
    France

    Site Not Available

  • Katholisches Klinikum Bochum gGMBH, Klinik für Kinder- und Jugendmedizin der Ruhr-Universität Bochum, St. Josef Hospital

    Bochum,
    Germany

    Site Not Available

  • Technische Universität Dresden, Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Kinder- und Jugendmedizin

    Dresden,
    Germany

    Site Not Available

  • Universitätsklinikum Essen,Pediatric Pulmonology and Cystic Fibrosis Center

    Essen,
    Germany

    Site Not Available

  • Medizinische Hochschule Hannover, Klinik für Pädiatrische Pneumologie, Allergologie und Neonatologie

    Hannover,
    Germany

    Site Not Available

  • Universitätsklinikum Jena, Klinik für Kinder- und Jugendmedizin, Pädiatrische Pneumologie/Allergologie/Mukoviszidose-Zentrum

    Jena,
    Germany

    Site Not Available

  • Cystic Fibrosis Department, "Agia Sofia" Children's Hospital

    Athens,
    Greece

    Site Not Available

  • Cystic Fibrosis Center, 3rd Paediatric Dept, Aristotle University of Thessaloniki

    Thessaloniki,
    Greece

    Site Not Available

  • Cork University Hospital

    Cork,
    Ireland

    Site Not Available

  • ASST Spedali Civili Paediatric department

    Brescia,
    Italy

    Active - Recruiting

  • IRCCS Istituto Giannina Gaslini

    Genoa,
    Italy

    Site Not Available

  • University of Parma Department of Medicine and Surgery

    Parma,
    Italy

    Site Not Available

  • IRCCS Ospedale Pediatrico Bambino Gesù

    Rome,
    Italy

    Active - Recruiting

  • University Medical Center Groningen (UMCG)

    Groningen,
    Netherlands

    Site Not Available

  • Radboud University Medical Center (RUMC)

    Nijmegen,
    Netherlands

    Site Not Available

  • Erasmus Medical Center (EMC)

    Rotterdam,
    Netherlands

    Site Not Available

  • University Medical Center Utrecht (UMCU)

    Utrecht,
    Netherlands

    Site Not Available

  • Centro Hospitalar Universitário Lisboa Norte EPE

    Lisbon,
    Portugal

    Site Not Available

  • Hospital Universitario Materno Infantil Reina Sofia

    Córdoba,
    Spain

    Site Not Available

  • Hospital Universitario 12 de Octubre,Unidad Multidisciplinar Fibrosis Quística

    Madrid,
    Spain

    Site Not Available

  • Hospital Universitario La Paz

    Madrid,
    Spain

    Site Not Available

  • Hospital Universitario Ramón y Cajal

    Madrid,
    Spain

    Site Not Available

  • University Children's Hospital Zurich

    Zürich,
    Switzerland

    Site Not Available

  • Birmingham Women's and Children's NHS Foundation Trust

    Birmingham,
    United Kingdom

    Site Not Available

  • University Hospital Nottingham (Queens Medical Centre)

    Nottingham,
    United Kingdom

    Site Not Available

  • Sheffield Childrens NHS Foundation Trust

    Sheffield,
    United Kingdom

    Site Not Available

  • University Hospital Southampton NHS FT

    Southampton,
    United Kingdom

    Site Not Available

  • University Hospitals of North Midlands NHS Trust

    Stoke-on-Trent,
    United Kingdom

    Site Not Available

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