Validation of Respiratory Epithelial Functional Assessment to Predict Clinical Efficacy of Orkambi®. Pathway to Personalized Therapy in Cystic Fibrosis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 91
- 试验地点
- 2
- 主要终点
- Percentage of FEV1
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Percentage of FEV1
时间窗: Baseline, Week 24
Absolute change in the percentage of predicted forced expiratory volume in 1 second (%FEV1) from baseline to week 24 of Orkambi®
次要结局
- Z-score of FEV1(Baseline, Week 24, week 48)
- Lung clearance index(Baseline, Week 48)
- Area under the curve (AUC) of Lumacaftor/Ivacaftor(Week 24, week 48)
- % of RFC(Baseline, Week 24 and week 48)
- colony forming unit (CFU)(Baseline, Week 24 and week 48)
- Level in Forskolin/IBMXdependant Short Circuit Current(Baseline)
- Percentage of FEV1(Week 48)
- Height(Baseline, Week 24 and week 48)
- Sweat Cl-(Baseline, Week 48)
- % of FVC(Baseline, Week 24 and week 48)
- Weight(Baseline, Week 24 and week 48)
- percentage of cells displaying apical staining(baseline)
- Number of exacerbations(Baseline, Week 48)
- Drug concentrations of Lumacaftor/Ivacaftor(Week 24, week 48)