Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia
Condition: Primary Ciliary Dyskinesia
MeSH terms: Ciliary Motility Disorders; Dyskinesias
Intervention: VX-371; Hypertonic Saline; Placebo (0.17% saline); VX-371 + HS; Ivacaftor
Intervention MeSH terms: Ivacaftor
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 123.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

Summary:

      To evaluate the safety and efficacy of treatment with VX-371 with and without ivacaftor, and
      the effect of VX-371 with and without ivacaftor on quality of life (QOL) in subjects with
      primary ciliary dyskinesia (PCD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  The subject must have evidence supportive of a PCD diagnosis.

          -  Subjects with percent predicted FEV1 of ≥40 to <90 percentage points

          -  Non-smoker for at least 90 days prior to the Screening Visit and less than a 5
             pack-year lifetime history of smoking

          -  Stable regimen of medications and chest physiotherapy for the 28 days prior to Day 1

          -  If currently using daily inhaled HS, must be able to discontinue its use for the
             duration of the study.

          -  If taking daily chronic or chronic cycling antibiotics, has been on a consistent
             regimen for at least 4 months prior to the Screening Visit.

          -  Clinically stable (as deemed by the investigator) for at least 14 days prior to the
             Screening Visit

          -  Female subjects of childbearing potential must have a negative serum pregnancy test at
             the Screening Visit. Subjects of childbearing potential and who are sexually active
             must meet the contraception requirements.

        Exclusion Criteria:

          -  Diagnosis of CF based on results of sweat chloride or nasal potential difference (NPD)
             tests or presence of 2 CF-causing mutations in CFTR gene.

          -  History of any organ transplantation or lung resection or chest wall surgery.

          -  Significant congenital heart defects, other than a laterality defect, at the
             discretion of the investigator

          -  Diagnosis of Cri du chat syndrome (chromosome 5p deletion syndrome).

          -  Inability to withhold short-acting bronchodilator use for 4 hours prior to clinic
             visit and long-acting bronchodilator use the night before the first and last clinic
             visit of each treatment period.

          -  Use of diuretics (including amiloride) or renin-angiotensin antihypertensive drugs

          -  Symptoms of acute upper or lower respiratory tract infection, acute pulmonary
             exacerbation, or treatment or was treated with systemic antibiotics for ear or sinus
             disease within 28 days before Day 1 (topical otic antibiotics allowed).

          -  History of significant intolerance to inhaled HS

          -  Pregnant and/or nursing females

          -  Any clinically significant laboratory abnormalities

          -  History of chronic B. cepacia complex or M. abscessus or M. avium

          -  Surgery that required general anesthesia and hospitalization within 3 months of Day 1

        Additional Exclusion Criteria for Part B:

          -  In addition to the exclusion criteria above, subjects who participate in Part B and
             meet any of the following exclusion criteria will not be eligible to continue into
             Part B

          -  Unable to swallow tablets.

          -  Concomitant use of strong or moderate inhibitors or inducers of cytochrome P450 (CYP)
             3A, including consumption of certain herbal medications (e.g., St. John's Wort), and
             grapefruit/grapefruit juice.

          -  Known hypersensitivity to ivacaftor.