Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2018-002624-16 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| URC-CIC Paris Descartes Necker Cochin | OTHER |
Not provided
Not provided
Not provided
Not provided
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 OrkambiĀ® treated patients.
OrkambiĀ® 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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nasal brushing | Diagnostic Test | Nasal scrapping at visit V0 | ||
| Sputum sample | Other | Visit V0 : 1 Aliquot for Sputum biobank Visit V1 : 2 Aliquots
Visit V2 : 2 Aliquots
| ||
| blood sample | Other | Visit V0 : Additional 14 mL
Visit V1 : Additional 9 mL
Visit V2 : Additional 6 mL
| ||
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of FEV1 | Absolute change in the percentage of predicted forced expiratory volume in 1 second (%FEV1) from baseline to week 24 of OrkambiĀ® | Baseline, Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Z-score of FEV1 | Absolute change in the Z-score of forced expiratory volume in 1 second (FEV1) from baseline to week 24 and to week 48 | Baseline, Week 24, week 48 |
| Percentage of FEV1 | Absolute change in the percentage of predicted forced expiratory volume in 1 second (FEV1) from baseline through week 48 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| ISABELLE SERMET, PhD | Hospital Necker Enfants Malades | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| HĆ“pital Necker-Enfants Malades | Paris | Ćle-de-France Region | 75015 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38310629 | Result | Bouazza N, Urien S, Foissac F, Choupeaux L, Lui G, Froelicher Bournaud L, Rouillon S, Zheng Y, Bardin E, Stremler N, Bessaci K, Bihouee T, Coirier-Duet E, Marguet C, Deneuville E, Laurans M, Reix P, Gerardin M, Mittaine M, Epaud R, Thumerelle C, Weiss L, Berthaud R, Semeraro M, Treluyer JM, Benaboud S, Sermet-Gaudelus I. Lumacaftor/Ivacaftor Population Pharmacokinetics in Pediatric Patients with Cystic Fibrosis: A First Step Toward Personalized Therapy. Clin Pharmacokinet. 2024 Mar;63(3):333-342. doi: 10.1007/s40262-023-01342-3. Epub 2024 Feb 4. |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| C000599212 | lumacaftor, ivacaftor drug combination |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Week 48 |
| % of FVC | Absolute change in percent predicted of forced vital capacity (%FVC) from baseline through week 24 and 48 | Baseline, Week 24 and week 48 |
| % of RFC | Absolute change in percent predicted of Functional Residual Capacity (%RFC) from baseline through week 24 and 48 | Baseline, Week 24 and week 48 |
| Lung clearance index | Absolute change in lung clearance index 2.5 (LCI2.5) from baseline through Week 48 | Baseline, Week 48 |
| Height | Absolute change in height-for-age-z-score from baseline to week 24 and 48 | Baseline, Week 24 and week 48 |
| Weight | Absolute change in weight-for-age-z-score from baseline to week 24 and 48 | Baseline, Week 24 and week 48 |
| colony forming unit (CFU) | Absolute change in colony forming unit (CFU) of sputum microorganisms from baseline to week 24 and 48 | Baseline, Week 24 and week 48 |
| Number of exacerbations | Number of exacerbations to week 48 in comparison to the year previous treatment with OrkambiĀ® | Baseline, Week 48 |
| Sweat Cl- | Absolute change in sweat Cl- from baseline to week 48 | Baseline, Week 48 |
| Level in Forskolin/IBMXdependant Short Circuit Current | Level in Forskolin/IBMXdependant Short Circuit Current change in patient nasal epithelial (HNE) cells incubated with Lumacaftor/Ivacaftor | Baseline |
| percentage of cells displaying apical staining | Correction of CFTR expression at the apical membrane in HNE cells incubated with Lumacaftor/Ivacaftor, assessed by the percentage of cells displaying apical staining. | baseline |
| Area under the curve (AUC) of Lumacaftor/Ivacaftor | Pharmacokinetic parameters of Lumacaftor, M28-lumacaftor, Ivacaftor, M1-ivacaftor, and M6-ivacaftor | Week 24, week 48 |
| Drug concentrations of Lumacaftor/Ivacaftor | Pharmacokinetic parameters of Lumacaftor, M28-lumacaftor, Ivacaftor, M1-ivacaftor, and M6-ivacaftor | Week 24, week 48 |
| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |