Evaluation of the short-term effect of ORKAMBI on lung function in patients with cystic fibrosis who have two copies of the F508del mutation using functional respiratory imaging

• Register: EUCTR
• Last refreshed on: 6 April 2020
• Main ID: EUCTR2018-001573-24-BE
• Date of registration: 08/05/2018
• Prospective Registration: Yes
• Primary sponsor: Antwerp University Hospital
• Public title: Evaluation of the short-term effect of ORKAMBI on lung function in patients with cystic fibrosis who have two copies of the F508del mutation using functional respiratory imaging
• Scientific title: Functional Respiratory Imaging (FRI) to assess the short-term effect of the product ORKAMBI (lumacaftor/ ivacaftor) on lung function in ORKAMBI-naive patients with Cystic Fibrosis Homozygous for Phe508del.
• Date of first enrolment: 11/06/2018
• Target sample size: 20
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-001573-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Belgium

Contacts

• Name: Kinderpneumologie UZA
• Affiliation: Antwerp University Hospital

• Name: Kinderpneumologie UZA
• Affiliation: Antwerp University Hospital

Key inclusion & exclusion criteria

Inclusion criteria:
1. Documented diagnosis of CF (homozygous for the F508del mutation must be present, this should be documented in the medical history).
2. Age = 12 years
3. FEV1 ³ 50%
4. Signed informed consent. If patient is a minor, parents/guardians must give written informed consent
5. Patient must be on a stable regimen of CF medication for 4 weeks prior to Visit 1
Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. FEV1 < 50%
2. Anticipated requirement for hospitalization within the next three weeks
3. History of pneumothorax within the past 6 months prior to Visit 1
4. History of haemoptysis requiring embolization within the past 12 months prior to Visit 1
5. Unable or unwilling to complete study visits or provide follow-up data as required per the study protocol
6. Has taken Intravenous (IV) antibiotics within the past 4 weeks prior to Visit 1
7. Has ongoing exacerbation or Allergic bronchopulmonary aspergillosis (ABPA)
8. Pregnant or lactating female
9. Posttransplant patients
10. Patients with severe hepatic impairment


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Cystic Fibrosis Homozygous (homozygous for the F508del mutation)
MedDRA version: 20.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Trade Name: Orkambi
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: LUMACAFTOR
Other descriptive name: LUMACAFTOR
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: IVACAFTOR
CAS Number: 873054-44-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-

Primary Outcome(s)

Secondary Objective: Secondary outcome variables are Patient Reported Outcome, lung function tests, digital lung auscultation, exercise tolerance and exacerbation frequencies.

Timepoint(s) of evaluation of this end point: HRCT scans will be taken at baseline (visit 1) and after 3 months of treatment (Visit 4).

Main Objective: The primary objective of this study is to assess the efficacy of ORKAMBI on lung functionality across multiple FRI parameters.

Primary end point(s): FRI parameters:
• Specific airway resistance (siRaw)
• Specific Airway volumes (siVaw)

Secondary Outcome(s)

Secondary end point(s): FRI parameters:
• Lung and lobe volumes
• Internal airflow distribution
• Airway wall thickness
• Blood vessel volume
• Air trapping
• Deposition of inhaled medications

Spirometry measurements:
• FEV1
• FVC
• FEV1/FVC

Lung Clearance Index (LCI)

Exercise Tolerance:
• 6 Minute Walk Test

Patient Reported Outcome (PRO):
• Borg Category Ratio 10 Scale: measure of the present dyspnea and leg fatigue before and after exercise
• Cystic Fibrosis Questionnaire- Revised (CFQ-R) respiratory domain score: measure Health-Related Quality of Life

Exacerbation frequency:
• Exacerbations requiring oral antibiotics
• Exacerbations requiring intravenous antibiotics

Timepoint(s) of evaluation of this end point: HRCT scans will be taken at baseline (visit 1) and after 3 months of treatment (visit 4).

Spirometry will taken at baseline (visit 1), after 1 month of tratement (visit 2), after 2 months of treatment (visit 3) and after 3 months of teratment (visit 4).

LCI will be done at baseline (visit 1) and after 3 months of treatment (visit 4).

6 MWT and PRO will be done at baseline (visit 1) and after 3 months of treatment (visit 4).

Exacerbation frequency will be checked at every visit (1,2,3, and 4).

Secondary ID(s)

1.0-22/3/2018

Source(s) of Monetary Support

Vertex Pharmaceuticals Incorporated

Ethics review

Status: Approved
Approval date: 11/06/2018
Contact: