A Study to Evaluate the Safety and Efficacy of VX-371 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation

A Phase 2a, Randomized, Double-blind, Placebo-controlled, Incomplete Block, Crossover Study to Evaluate the Safety and Efficacy of VX-371 in Subjects Aged 12 Years or Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation, and Being Treated With Orkambi

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

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.