Functional Respiratory Imaging and Orkambi in CF

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

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.

Study Overview

• Status: Terminated
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Orkambi

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • Antwerp University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Antwerp

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Actual): April 1, 2020
• Study Completion (Actual): April 1, 2020

Study Registration Dates

• First Submitted: May 2, 2019
• First Submitted That Met QC Criteria: May 17, 2019
• First Posted (Actual): May 20, 2019

Study Record Updates

• Last Update Posted (Actual): April 8, 2020
• Last Update Submitted That Met QC Criteria: April 7, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: 2018-001573-24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No