Study of the Effect of VX-770 on Hyperpolarized Helium-3 Magnetic Resonance Imaging in Subjects With Cystic Fibrosis and the G551D Mutation
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: VX-770; Placebo
Intervention description: Tablet.; Tablet.
Intervention MeSH terms: Ivacaftor
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: Single (Participant)
Enrollment: 13.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

Summary:

      Cystic Fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance
      regulator (CFTR) gene. The encoded protein, CFTR, is an epithelial chloride ion channel
      responsible for aiding in the regulation of salt and water absorption and secretion in
      various tissues. Although the disease affects multiple organs, the leading cause of mortality
      is the progressive loss of lung function. Obstruction of airways with thick mucus, chronic
      bacterial infection of the airways, and inflammatory response are all thought to play a role
      in causing lung damage. Through its function as a chloride channel, CFTR is believed to be
      integral in epithelial ion and water transport and hence, maintaining the normal hydration of
      lung secretions.

      VX-770 (ivacaftor) is a potent and selective potentiator of wild-type, G551D, F508del, and
      R117H forms of human CFTR. Based on in vitro studies and pharmacologic, pharmacokinetic (PK),
      and safety profiles, VX-770 has been selected for clinical development as a possible
      treatment for patients with CF.

      Hyperpolarized noble gas magnetic resonance imaging (HG-MRI) is a promising new means of
      assessing lung function by direct imaging of certain non-radioactive isotopes of an inert
      noble gas, such as helium or xenon. Through this technique, high-resolution 3-dimensional
      images of lung ventilation can be obtained in both pediatric and adult patients during a
      single short breath-hold following inhalation of the gas.

      This is a 2-part study to evaluate the effect of VX-770 on hyperpolarized helium-3 magnetic
      resonance imaging (3He-MRI), and to evaluate the safety and efficacy of VX-770 in subjects
      aged 12 years and older with CF who have the G551D-CFTR mutation. Part A is a single-blind,
      placebo-controlled study that includes 4 weeks of VX-770 treatment and 4 weeks of placebo
      treatment. Part B is an open-label, 48 week study of long-term effect of VX 770 on
      hyperpolarized 3He-MRI.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female with Cystic Fibrosis

          -  Must have the G551D-CFTR mutation on at least 1 allele

          -  FEV1 ≥40% of predicted normal for age, gender, and height at Screening

          -  12 years of age or older

          -  Must be able to swallow tablets

        Exclusion Criteria:

          -  History of solid organ or hematological transplantation

          -  Ongoing participation in another therapeutic clinical study or prior participation in
             an investigational drug study within the 30 days prior to screening

          -  Use of inhaled hypertonic saline treatment within 14 days prior to the Screening Visit

          -  Extensive body tattoos or other physical features that will confound MRI