Functional Respiratory Imaging and Orkambi in CF

Phase 4

Terminated

• Conditions: Cystic Fibrosis
• Interventions: Drug: Orkambi

• Registration Number: NCT03956589
• Lead Sponsor: University Hospital, Antwerp

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-10-01
• Study First Submitted: 2019-05-02
• Study First Submitted QC: 2019-05-17
• Study First Posted: 2019-05-20
• Status Verified: 2020-04
• Primary Completion: 2020-04-01
• Study Completion: 2020-04-01
• Last Update Submitted: 2020-04-07
• Last Update Posted: 2020-04-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 12

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Orkambi open-label arm	Orkambi	Open-label study: all subjects will receive Orkambi during 3 months.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Exacerbation frequency	baseline and after three months of therapy	Number of cystic fibrosis exacerbations
airway resistances	baseline and after three months of therapy	calculated using body plethysmography
Lung clearance index	baseline and after three months of therapy	Marker of lung ventilation inhomogeneity
Digital lung auscultation	baseline and after three months of therapy	Digital analysis of digital lung sounds obtained by a digital stethoscope
Internal Airflow Distribution	baseline and after three months of therapy	calculated using thorax HRCT
Dynamic lung volumes	baseline and after three months of therapy	calculated using spirometry
Air Trapping	baseline and after three months of therapy	calculated using thorax HRCT
Airway Wall Volume	baseline and after three months of therapy	calculated using thorax HRCT
Aerosol Deposition	baseline and after three months of therapy	calculated using thorax HRCT
Static lung volumes	baseline and after three months of therapy	calculated using body plethysmography
6-minute walking test	baseline and after three months of therapy	Marker of fitness for daily activities
Sweat chloride test	baseline and after three months of therapy	Chloride values in sweat chloride test
CFQ-R	baseline and after three months of therapy	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.

Trial Locations

Locations (1)

Antwerp University Hospital; 🇧🇪 Edegem, Belgium