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

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 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.