Clinical trial NCT03894657: Validation of Respiratory Epithelial Functional Assessment to Predict Clinical Efficacy of Orkambi®.
Official title: Validation of Respiratory Epithelial Functional Assessment to Predict Clinical Efficacy of Orkambi®. Pathway to Personalized Therapy in Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cystic Fibrosis
Homozygous F508del Mutation
Keywords: CYSTIC FIBROSIS
ORKAMBI
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2019-03-28
Enrollment: 91
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of FEV1
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Z-score of FEV1
timeFrame: Baseline, Week 24, week 48
measure: Percentage of FEV1
timeFrame: Week 48
measure: % of FVC
timeFrame: Baseline, Week 24 and week 48
measure: % of RFC
timeFrame: Baseline, Week 24 and week 48
measure: Lung clearance index
timeFrame: Baseline, Week 48
measure: Height
timeFrame: Baseline, Week 24 and week 48
measure: Weight
timeFrame: Baseline, Week 24 and week 48
measure: colony forming unit (CFU)
timeFrame: Baseline, Week 24 and week 48
measure: Number of exacerbations
timeFrame: Baseline, Week 48
measure: Sweat Cl-
timeFrame: Baseline, Week 48
measure: Level in Forskolin/IBMXdependant Short Circuit Current
timeFrame: Baseline
measure: percentage of cells displaying apical staining
timeFrame: baseline
measure: Area under the curve (AUC) of Lumacaftor/Ivacaftor
timeFrame: Week 24, week 48
measure: Drug concentrations of Lumacaftor/Ivacaftor
timeFrame: Week 24, week 48
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
state: ILE DE France
Study officials:
affiliation: Hospital Necker Enfants Malades
name: ISABELLE SERMET, PhD
role: PRINCIPAL_INVESTIGATOR
References: