A Study to Evaluate the Safety and Efficacy of Long Term Treatment With VX-661 in Combination With Ivacaftor in Subjects With Cystic Fibrosis Who Have an F508del-CFTR Mutation

Inclusion Criteria:

Part A:

- Subjects entering the Treatment Cohort must meet all of the following criteria:

- Elect to enroll in the Treatment Cohort

- Completed study drug Treatment Period in a parent study (NCT02070744, NCT02347657,
NCT02516410, NCT02392234, NCT02412111) or study drug treatment and the Safety Follow
up Visit for subjects from NCT02508207.

- Willing to remain on a stable CF regimen through the Safety Follow-up Visit.

- Subjects re-enrolling in the Part A Treatment Cohort must meet all of the following
criteria:

- Previously received at least 4 weeks of study drug before discontinuing in Part A
of Study NCT02565914 to participate in another qualified Vertex study.

- Completed the last required visit of another qualified Vertex study before or
during the Returning Visit in Part A Study NCT02565914.

- Subjects entering the Part A Observational Cohort must meet the following criteria:

- <18 years of age (age on the date of informed consent/assent in the parent study)

- Completed study drug Treatment Period in a parent study or study drug treatment
and the Safety Follow up Visit for subjects from NCT02508207, but do not elect to
enroll in the NCT02565914 Treatment Cohort; or

- Received at least 4 weeks of study drug treatment and completed visits up to the
last scheduled visit of the Treatment Period of a parent study (and the Safety
Follow up Visit for subjects from NCT02508207), but do not meet eligibility
criteria for enrollment into the Treatment Cohort

Part B:

Part B Subjects who meet all of the following inclusion criteria will be eligible for Part
B.

- Did not withdraw consent from the parent study or Part A of Study NCT02565914.

- Completed study drug treatment during the Treatment Period in Part A of NCT02565914,
Studies NCT02730208 or NCT03150719, or other eligible Vertex studies.

- Willing to remain on a stable CF medication (and supplement) regimen through the 96
week visit of Study NCT02565914.

Subjects re enrolling in Part B must meet all of the following criteria:

- Previously received at least 4 weeks of study drug before discontinuing Study
NCT02565914 to participate in another qualified Vertex study, which is defined as a
Vertex study of investigational CFTR modulators that allows participation of subjects
in Study NCT02565914.

- Completed the last required visit of another qualified Vertex study before or during
the Returning Visit in Part B.

- Willing to remain on a stable CF medication (and supplement) regimen through the 96
week visit in Part B.

Exclusion Criteria:

- History of any comorbidity that, in the opinion of the investigator, might confound
the results of the study or pose an additional risk to the subject.

- Pregnant and nursing females.

- Sexually active subjects of reproductive potential who are not willing to follow the
contraception requirements.

- History of drug intolerance in the parent study that would pose an additional risk to
the subject.

- Participation in an investigational drug trial (including studies investigating
VX-661/ivacaftor or lumacaftor/ivacaftor) other than the parent studies of NCT02565914
or other eligible Vertex studies investigating VX-661 in combination with ivacaftor,
or use of a commercially available CFTR modulator.

Other protocol defined Inclusion/Exclusion criteria may apply.