A Study to Evaluate the Safety and Efficacy of VX-371 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: VX-371 + HS; Hypertonic saline; Placebo; Orkambi; VX-371
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: 147.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the safety and efficacy of treatment with VX-371 in
      hypertonic saline compared to hypertonic saline alone in subjects with cystic fibrosis (CF)
      who are ≥12 years of age, homozygous for the F508del-cystic fibrosis transmembrane
      conductance regulator (CFTR) mutation, and being treated with Orkambi
    

Eligibility criteria:

        Inclusion Criteria:

          -  Willing and able to use the delivery device as directed by the study manual.

          -  Confirmed diagnosis of CF, defined as a sweat chloride value ≥60 mmol/L by
             quantitative pilocarpine iontophoresis.

          -  Homozygous for the F508del CFTR mutation. If the CFTR screening genotype result is not
             received before randomization, a previous CFTR genotype lab report may be used to
             establish eligibility.

          -  Percent predicted forced expiratory volume at one second (FEV1) of ≥40 to <90
             percentage points adjusted for age, sex, and height according to the Global Lung
             Initiative (GLI) at the Screening Visit.

          -  Willing to discontinue physician-prescribed saline use.

          -  Female subjects of childbearing potential with a negative serum pregnancy test at the
             Screening Visit.

        Exclusion Criteria:

          -  History of any comorbidity, which in the opinion of the investigator, might confound
             the results of the study or pose an additional risk in administering study drug to the
             subject.

          -  Any clinically significant laboratory abnormalities at the Screening Visit that would
             interfere with the study assessments or pose an undue risk for the subject.

          -  An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in
             therapy (including antibiotics) for pulmonary disease within 28 days before Day 1
             (first dose of study drug).

          -  A 12 lead ECG demonstrating QTcF >450 msec at the Screening Visit.

          -  History of solid organ or hematological transplantation.

          -  Used diuretics or renin-angiotensin aldosterone system antihypertensive drugs in the
             28 days prior to Screening or an anticipated need for any of these medications during
             the study.

          -  Ongoing or prior participation in an investigational drug study within 30 days of the
             Screening Visit.

          -  Inability to withhold short-acting, long-acting, or once-daily, long-acting
             bronchodilator use for 4, 12, or 24 hours prior to clinic visit, respectively.

          -  History of significant intolerance to inhaled saline, or intolerance to the single
             dose of saline at Screening

          -  Known hypersensitivity or history of intolerance to Orkambi.

          -  Pregnant and nursing females.

          -  Subjects who have participated in Parion Sciences Study NCT02343445.