Validation of Respiratory Epithelial Functional Assessment to Predict Clinical Efficacy of Orkambi®. (PREDICT-CF)

Assistance Publique - Hôpitaux de Paris

Status

Completed

Conditions

Homozygous F508del Mutation

Cystic Fibrosis

Treatments

Other: Sputum sample

Other: blood sample

Diagnostic Test: Nasal brushing

Drug: Orkambi

Study type

Interventional

Funder types

Other

Identifiers

NCT03894657

P170907J

2018-002624-16 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment

91 patients

Sex

All

Ages

5+ years old

Volunteers

No Healthy Volunteers

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