MedPath

CPET in CF Patients With One G551D Mutation Taking VX770

Phase 4
Conditions
Cystic Fibrosis
Interventions
Drug: placebo
Registration Number
NCT01937325
Lead Sponsor
The Alfred
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
20
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).

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
PlaceboplaceboMatching placebo
Ivacaftorivacaftor150mg orally twice daily
Primary Outcome Measures
NameTimeMethod
exercise capacityone month, 3 months

Respiratory exercise testing, including spirometry and V02 max.

Secondary Outcome Measures
NameTimeMethod
Inflammatory profileOne month, 3 months

Cytokine levels (IL-1β, IL-6, TNFα, IL-8, VEGF \& Activin A) determined using cytometric bead analysis and / or ELISA

Trial Locations

Locations (1)

The Alfred

🇦🇺

Melbourne, Victoria, Australia

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