Functional Respiratory Imaging and Orkambi in CF

Study Overview
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Brief Summary
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Open-label study to investigate the effects of Orkambi in CF patients homozygous for the F508del mutation by functional respiratory imaging. Primary endpoints in this study are the changes in Specific airway volumes (siVaw) and Specific Airway resistance (siRaw). A total of 20 ORKAMBI-naive patients with Cystic Fibrosis, homozygous for the F508del mutation will be included in this open label study and will be followed through 3 months of treatment. The treatment will be started after all assessments are performed at visit 1. After the start of the treatment some baseline measurements will be repeated throughout the 3-month treatment period. The patient will be asked to visit the hospital monthly. All study visits should be scheduled around the same time.

Official Title
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Functional Respiratory Imaging (FRI) to Assess the Short-term Effect of the Product ORKAMBI (Lumacaftor/ Ivacaftor) on Lung Function in ORKAMBInaive Patients With Cystic Fibrosis Homozygous for Phe508del

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Orkambi


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of CF (homozygous for the F508del mutation must be present, this should be documented in the medical history). Age ≥ 12 years FEV1 > 50% Signed informed consent. If patient is a minor, parents/guardians must give written informed consent Patient must be on a stable regimen of CF medication for 4 weeks prior to Visit Exclusion Criteria: FEV1 < 50% Anticipated requirement for hospitalization within the next three weeks History of pneumothorax within the past 6 months prior to Visit 1 History of haemoptysis requiring embolization within the past 12 months prior to Visit 1 Unable or unwilling to complete study visits or provide follow-up data as required per the study protocol Has taken Intravenous (IV) antibiotics within the past 4 weeks prior to Visit 1 Has ongoing exacerbation or Allergic bronchopulmonary aspergillosis (ABPA) Pregnant or lactating female Posttransplant patients Patients with severe hepatic impairment

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orkambi open-label arm<br>Open-label study: all subjects will receive Orkambi during 3 months. | Drug: Orkambi<br>* Open label of Orkambi treatment during 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in specific image-based airway resistance (siRaw) | Change in CFD-based airway resistance normalized by the lung volume | baseline and after three months of therapy | 
| Change in specific image-based airway volumes (siVaw) | change in CT-based airway volumes normalized by the lung volume | baseline and after three months of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Internal Airflow Distribution | calculated using thorax HRCT | baseline and after three months of therapy | 
| Air Trapping | calculated using thorax HRCT | baseline and after three months of therapy | 
| Airway Wall Volume | calculated using thorax HRCT | baseline and after three months of therapy | 
| Aerosol Deposition | calculated using thorax HRCT | baseline and after three months of therapy | 
| Dynamic lung volumes | calculated using spirometry | baseline and after three months of therapy | 
| Static lung volumes | calculated using body plethysmography | baseline and after three months of therapy | 
| airway resistances | calculated using body plethysmography | baseline and after three months of therapy | 
| Lung clearance index | Marker of lung ventilation inhomogeneity | baseline and after three months of therapy | 
| 6-minute walking test | Marker of fitness for daily activities | baseline and after three months of therapy | 
| Sweat chloride test | Chloride values in sweat chloride test | baseline and after three months of therapy | 
| CFQ-R | standardized measures of quality of life will be administered to subject and to parents of subjects under 18 years of age. Disease-specific instrument designed to measure impact on overall health, daily life, perceived well-being and symptoms. Developed specifically for use in patients with a diagnosis of cystic fibrosis. Scores range from 0 to 100, with higher scores indicating better health. | baseline and after three months of therapy | 
| Digital lung auscultation | Digital analysis of digital lung sounds obtained by a digital stethoscope | baseline and after three months of therapy | 
| Exacerbation frequency | Number of cystic fibrosis exacerbations | baseline and after three months of therapy |