CPET in CF Patients With One G551D Mutation Taking VX770

Study Overview
=================
Brief Summary
-----------------
Ivacaftor will restore CFTR function in treated CF patients with the G551D mutation. Improvement in ventilation, salt balance and well-being will contribute to better exercise capacity at all levels of lung function. While potential improvements may be variable across the spectrum of lung function, even small gains at low levels of FEV1 may have significant benefit for some subjects.

Detailed Description
-----------------
The Alfred CF Service is ready to initiate therapy with VX-770 in it's cohort. Investigators therefore have an opportunity to examine correlates between improvements in lung function, exercise capacity, inflammatory markers and indices of wellbeing in CF that may not be repeatable in a single cohort. Investigators propose a double-blind, placebo-controlled cross-over study of 20 patients currently awaiting initiation of ivacaftor therapy. Patients enrolled in the study will be asked to undergo screening (day -28), and baseline assessments (day 0) and re-assessment studies (day 28) after treatment period 1, followed by baseline assessment at the beginning of treatment period 2 (day 56) and at the conclusion of treatment period 2 (day 84). A further assessment (day 224) will be performed 140 (+/-7) days following commencement on open label Ivacaftor. After satisfying eligibility criteria, subjects will be randomly assigned to initial active treatment or placebo following a 4 week run-in period. After completion of period 1 and a 4 week washout period, subjects will cross-over to the alternative treatment. After 4 weeks of period 2, subjects will undergo final assessment as shown in the diagram below. However participants choosing not to continue taking ivacaftor in a Named Patient Program or another similar program run by Vertex Pharmaceuticals, Inc., ('Vertex'), at the end of the study period will be required to undergo a Safety Follow-Up visit 28 days after the final dose of study drug. Safety Follow-Up assessments will not include the CPET.

Official Title
-----------------
Airway Infection, Inflammatory Markers and Exercise Capacity in Patients With Cystic Fibrosis and at Least One G551D Mutation Taking VX770 (Ivacaftor)

Conditions
-----------------
Cystic Fibrosis

Intervention / Treatment
-----------------
* Drug: ivacaftor
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All participants will have CF proven based on established criteria (sweat test, genotype and phenotype). All participants will have at least one copy of the G551D mutation. All will be able to perform an exercise study and complete study questionnaires and assessments. Age range will be between 16 and 75 years of age. Lung function inclusion will be above 25% predicted FEV1. Exclusion Criteria: Participants will not be included if they are unable to complete study assessments or have had a known adverse reaction to Ivacaftor. Female participants will be excluded if found to return a positive pregnancy test at screening. Participants will be excluded if using St. John's Wort or rifampicin (strong CYP3A inducers). Participants with significant liver dysfunction will be excluded (ALT or ALT above 5 times upper limit of normal).

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ivacaftor<br>150mg orally twice daily | Drug: ivacaftor<br>* active arm<br>* Other names: Kalydeco;|
| Placebo Comparator: Placebo<br>Matching placebo | Drug: placebo<br>* active arm<br>* Other names: ivacaftor matched placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| exercise capacity | Respiratory exercise testing, including spirometry and V02 max. | one month, 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory profile | Cytokine levels (IL-1β, IL-6, TNFα, IL-8, VEGF & Activin A) determined using cytometric bead analysis and / or ELISA | One month, 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Eligible CF patients with G551D gene mutation