Ignite Creation Date:
2025-12-24 @ 6:33 PM
Ignite Modification Date:
2026-02-01 @ 9:14 PM
Study NCT ID:
NCT03894657
Status:
COMPLETED
Last Update Posted:
2025-08-29
First Post:
2019-02-12
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Validation of Respiratory Epithelial Functional Assessment to Predict Clinical Efficacy of Orkambi®.
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003550', 'term': 'Cystic Fibrosis'}], 'ancestors': [{'id': 'D010182', 'term': 'Pancreatic Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D007232', 'term': 'Infant, Newborn, Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D001800', 'term': 'Blood Specimen Collection'}, {'id': 'C000599212', 'term': 'lumacaftor, ivacaftor drug combination'}], 'ancestors': [{'id': 'D013048', 'term': 'Specimen Handling'}, {'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D011677', 'term': 'Punctures'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}, {'id': 'D008919', 'term': 'Investigative Techniques'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 91}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2019-12-18', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-05', 'completionDateStruct': {'date': '2022-05-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-08-22', 'studyFirstSubmitDate': '2019-02-12', 'studyFirstSubmitQcDate': '2019-03-27', 'lastUpdatePostDateStruct': {'date': '2025-08-29', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2019-03-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-11-25', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Percentage of FEV1', 'timeFrame': 'Baseline, Week 24', 'description': 'Absolute change in the percentage of predicted forced expiratory volume in 1 second (%FEV1) from baseline to week 24 of Orkambi®'}], 'secondaryOutcomes': [{'measure': 'Z-score of FEV1', 'timeFrame': 'Baseline, Week 24, week 48', 'description': 'Absolute change in the Z-score of forced expiratory volume in 1 second (FEV1) from baseline to week 24 and to week 48'}, {'measure': 'Percentage of FEV1', 'timeFrame': 'Week 48', 'description': 'Absolute change in the percentage of predicted forced expiratory volume in 1 second (FEV1) from baseline through week 48'}, {'measure': '% of FVC', 'timeFrame': 'Baseline, Week 24 and week 48', 'description': 'Absolute change in percent predicted of forced vital capacity (%FVC) from baseline through week 24 and 48'}, {'measure': '% of RFC', 'timeFrame': 'Baseline, Week 24 and week 48', 'description': 'Absolute change in percent predicted of Functional Residual Capacity (%RFC) from baseline through week 24 and 48'}, {'measure': 'Lung clearance index', 'timeFrame': 'Baseline, Week 48', 'description': 'Absolute change in lung clearance index 2.5 (LCI2.5) from baseline through Week 48'}, {'measure': 'Height', 'timeFrame': 'Baseline, Week 24 and week 48', 'description': 'Absolute change in height-for-age-z-score from baseline to week 24 and 48'}, {'measure': 'Weight', 'timeFrame': 'Baseline, Week 24 and week 48', 'description': 'Absolute change in weight-for-age-z-score from baseline to week 24 and 48'}, {'measure': 'colony forming unit (CFU)', 'timeFrame': 'Baseline, Week 24 and week 48', 'description': 'Absolute change in colony forming unit (CFU) of sputum microorganisms from baseline to week 24 and 48'}, {'measure': 'Number of exacerbations', 'timeFrame': 'Baseline, Week 48', 'description': 'Number of exacerbations to week 48 in comparison to the year previous treatment with Orkambi®'}, {'measure': 'Sweat Cl-', 'timeFrame': 'Baseline, Week 48', 'description': 'Absolute change in sweat Cl- from baseline to week 48'}, {'measure': 'Level in Forskolin/IBMXdependant Short Circuit Current', 'timeFrame': 'Baseline', 'description': 'Level in Forskolin/IBMXdependant Short Circuit Current change in patient nasal epithelial (HNE) cells incubated with Lumacaftor/Ivacaftor'}, {'measure': 'percentage of cells displaying apical staining', 'timeFrame': 'baseline', 'description': 'Correction of CFTR expression at the apical membrane in HNE cells incubated with Lumacaftor/Ivacaftor, assessed by the percentage of cells displaying apical staining.'}, {'measure': 'Area under the curve (AUC) of Lumacaftor/Ivacaftor', 'timeFrame': 'Week 24, week 48', 'description': 'Pharmacokinetic parameters of Lumacaftor, M28-lumacaftor, Ivacaftor, M1-ivacaftor, and M6-ivacaftor'}, {'measure': 'Drug concentrations of Lumacaftor/Ivacaftor', 'timeFrame': 'Week 24, week 48', 'description': 'Pharmacokinetic parameters of Lumacaftor, M28-lumacaftor, Ivacaftor, M1-ivacaftor, and M6-ivacaftor'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['CYSTIC FIBROSIS', 'ORKAMBI'], 'conditions': ['Cystic Fibrosis', 'Homozygous F508del Mutation']}, 'referencesModule': {'references': [{'pmid': '38310629', 'type': 'BACKGROUND', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nThe 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '5 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Homozygous F508del patient aged 5 years or older\n* Patient with an indication for Orkambi® treatment according to the marketing authorization application\n* Patient never received Orkambi® in the past\n* Patient able to perform FEV1\n* 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\n\nExclusion Criteria:\n\n* Homozygous F508del patients who do not meet the treatment indications according to the marketing authorization application\n* Patients refusing Orkambi®\n* CF patients not homozygous for the p.Phe508del mutation\n* Active smoker\n* Severe nasal mucosa disrepair\n* Contraindications to xylocaine anesthesia,\n* Participation with another interventional study with drug"}, 'identificationModule': {'nctId': 'NCT03894657', 'acronym': 'PREDICT-CF', 'briefTitle': 'Validation of Respiratory Epithelial Functional Assessment to Predict Clinical Efficacy of Orkambi®.', 'organization': {'class': 'OTHER', 'fullName': 'Assistance Publique - Hôpitaux de Paris'}, 'officialTitle': 'Validation of Respiratory Epithelial Functional Assessment to Predict Clinical Efficacy of Orkambi®. Pathway to Personalized Therapy in Cystic Fibrosis', 'orgStudyIdInfo': {'id': 'P170907J'}, 'secondaryIdInfos': [{'id': '2018-002624-16', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'interventions': [{'name': 'Nasal brushing', 'type': 'DIAGNOSTIC_TEST', 'description': 'Nasal scrapping at visit V0'}, {'name': 'Sputum sample', 'type': 'OTHER', 'description': 'Visit V0 : 1 Aliquot for Sputum biobank\n\nVisit V1 : 2 Aliquots\n\n* for Sputum biobank\n* for pharmacokinetic (PK) study\n\nVisit V2 : 2 Aliquots\n\n* for Sputum biobank\n* for pharmacokinetic (PK) study'}, {'name': 'blood sample', 'type': 'OTHER', 'description': 'Visit V0 : Additional 14 mL\n\n* 5 mL in ethylenediaminetetraacetic acid (EDTA) tube for DNA Analysis\n* 3 mL in Dry tube for Serum biobank\n* 6 mL in acid citrate dextrose (ACD) tube for peripheral blood mononuclear cell (PBMC) biobank\n\nVisit V1 : Additional 9 mL\n\n* 2x3 mL in dry tube for pharmacokinetic (PK) study\n* 3 mL in Dry tube for Serum biobank\n\nVisit V2 : Additional 6 mL\n\n* 3 mL in dry tube for pharmacokinetic (PK) study\n* 3 mL in Dry tube for Serum biobank'}, {'name': 'Orkambi', 'type': 'DRUG', 'description': 'Study the predictive value for improvement of the respiratory function after 24 weeks of Orkambi treatment.\n\nOrkambi treatment is part of usual care.'}]}, 'contactsLocationsModule': {'locations': [{'zip': '75015', 'city': 'Paris', 'state': 'Île-de-France Region', 'country': 'France', 'facility': 'Hôpital Necker-Enfants Malades', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}], 'overallOfficials': [{'name': 'ISABELLE SERMET, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Hospital Necker Enfants Malades'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Assistance Publique - Hôpitaux de Paris', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}