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Completed

NCT Number: NCT03894657

Validation of Respiratory Epithelial Functional Assessment to Predict Clinical Efficacy of Orkambi®.

The purpose of the study is to investigate whether the correction of CFTR function by Lumacaftor/Ivacaftor in a patient-derived primary nasal cell model is a surrogate biomarker for respiratory improvement in Orkambi® treated patients.

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Key information

Conditions

Cystic Fibrosis Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Genetic Diseases, Inborn Homozygous F508del Mutation Infant, Newborn, Diseases Lung Diseases Pancreatic Diseases Respiratory Tract Diseases

Age range

5 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Hôpital Necker-Enfants Malades

Paris, Île-de-France Region, 75015, France

About this study

Orkambi® is a combination of Ivacaftor (a CFTR channel potentiator) and Lumacaftor (a corrector partially rescuing the traffic of mutated CFTR). This treatment is now marketed in France for patients homozygotes for the mutation p.Phe508del, aged 12 and above. Systematic use of this product is a concern due to the lack of predictive markers of efficacy, the highly variable respiratory improvement in patients and potential serious side effects.

The purpose of this study is to investigate the predictive value for improvement of the respiratory function after 24 weeks of Orkambi treatment of an in vitro test. This test quantifies the correction of CFTR activity as assessed by the change of cyclic AMP (cAMP) dependant chloride (Cl-) secretion in patient derived Human Nasal Epithelial (HNE) derived primary culture after Lumacaftor/Ivacaftor 48 hours incubation.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Homozygous F508del patient aged 5 years or older
  • Patient with an indication for Orkambi® treatment according to the marketing authorization application
  • Patient never received Orkambi® in the past
  • Patient able to perform FEV1
  • Signed Informed consent form by the patient (if aged ≥ 18 years), or by parents / legal guardian and patient's agreement (if aged < 18 years) Patient affiliated to the health insurance system

Exclusion criteria

  • Homozygous F508del patients who do not meet the treatment indications according to the marketing authorization application
  • Patients refusing Orkambi®
  • CF patients not homozygous for the p.Phe508del mutation
  • Active smoker
  • Severe nasal mucosa disrepair
  • Contraindications to xylocaine anesthesia,
  • Participation with another interventional study with drug

Treatment and study plan

Nasal brushing

Diagnostic Test

Nasal scrapping at visit V0

Sputum sample

Other

Visit V0 : 1 Aliquot for Sputum biobank

Visit V1 : 2 Aliquots

  • for Sputum biobank
  • for pharmacokinetic (PK) study

Visit V2 : 2 Aliquots

  • for Sputum biobank
  • for pharmacokinetic (PK) study

blood sample

Other

Visit V0 : Additional 14 mL

  • 5 mL in ethylenediaminetetraacetic acid (EDTA) tube for DNA Analysis
  • 3 mL in Dry tube for Serum biobank
  • 6 mL in acid citrate dextrose (ACD) tube for peripheral blood mononuclear cell (PBMC) biobank

Visit V1 : Additional 9 mL

  • 2x3 mL in dry tube for pharmacokinetic (PK) study
  • 3 mL in Dry tube for Serum biobank

Visit V2 : Additional 6 mL

  • 3 mL in dry tube for pharmacokinetic (PK) study
  • 3 mL in Dry tube for Serum biobank

Orkambi

Drug

Study the predictive value for improvement of the respiratory function after 24 weeks of Orkambi treatment.

Orkambi treatment is part of usual care.

Primary outcomes

  1. Percentage of FEV1

    Time frame: Baseline, Week 24

    Absolute change in the percentage of predicted forced expiratory volume in 1 second (%FEV1) from baseline to week 24 of Orkambi®

Secondary outcomes

  1. Z-score of FEV1

    Time frame: Baseline, Week 24, week 48

    Absolute change in the Z-score of forced expiratory volume in 1 second (FEV1) from baseline to week 24 and to week 48

  2. Percentage of FEV1

    Time frame: Week 48

    Absolute change in the percentage of predicted forced expiratory volume in 1 second (FEV1) from baseline through week 48

  3. % of FVC

    Time frame: Baseline, Week 24 and week 48

    Absolute change in percent predicted of forced vital capacity (%FVC) from baseline through week 24 and 48

  4. % of RFC

    Time frame: Baseline, Week 24 and week 48

    Absolute change in percent predicted of Functional Residual Capacity (%RFC) from baseline through week 24 and 48

  5. Lung clearance index

    Time frame: Baseline, Week 48

    Absolute change in lung clearance index 2.5 (LCI2.5) from baseline through Week 48

  6. Height

    Time frame: Baseline, Week 24 and week 48

    Absolute change in height-for-age-z-score from baseline to week 24 and 48

  7. Weight

    Time frame: Baseline, Week 24 and week 48

    Absolute change in weight-for-age-z-score from baseline to week 24 and 48

  8. colony forming unit (CFU)

    Time frame: Baseline, Week 24 and week 48

    Absolute change in colony forming unit (CFU) of sputum microorganisms from baseline to week 24 and 48

  9. Number of exacerbations

    Time frame: Baseline, Week 48

    Number of exacerbations to week 48 in comparison to the year previous treatment with Orkambi®

  10. Sweat Cl-

    Time frame: Baseline, Week 48

    Absolute change in sweat Cl- from baseline to week 48

  11. Level in Forskolin/IBMXdependant Short Circuit Current

    Time frame: Baseline

    Level in Forskolin/IBMXdependant Short Circuit Current change in patient nasal epithelial (HNE) cells incubated with Lumacaftor/Ivacaftor

  12. percentage of cells displaying apical staining

    Time frame: baseline

    Correction of CFTR expression at the apical membrane in HNE cells incubated with Lumacaftor/Ivacaftor, assessed by the percentage of cells displaying apical staining.

  13. Area under the curve (AUC) of Lumacaftor/Ivacaftor

    Time frame: Week 24, week 48

    Pharmacokinetic parameters of Lumacaftor, M28-lumacaftor, Ivacaftor, M1-ivacaftor, and M6-ivacaftor

  14. Drug concentrations of Lumacaftor/Ivacaftor

    Time frame: Week 24, week 48

    Pharmacokinetic parameters of Lumacaftor, M28-lumacaftor, Ivacaftor, M1-ivacaftor, and M6-ivacaftor

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Collaborators

  • URC-CIC Paris Descartes Necker Cochin

Registry information

Official study title

Validation of Respiratory Epithelial Functional Assessment to Predict Clinical Efficacy of Orkambi®. Pathway to Personalized Therapy in Cystic Fibrosis

Acronym: PREDICT-CF

Important dates

Study start
2019
Primary completion
2021
Study completion
2022
First posted
Mar 28, 2019
Registry last updated
Mar 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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