Study of VX-661 Alone and in Combination With Ivacaftor in Subjects Homozygous or Heterozygous to the F508del-Cystic Fibrosis Transmembrane Conductance Regulator(CFTR) Mutation

This is a Phase 2, randomized, multicenter, double-blinded, placebo-controlled, study of
VX-661 monotherapy, and VX-661/ivacaftor co-therapy in participants with CF who are
homozygous or heterozygous for the F508del CFTR mutation.

This study is separated into seven groups: Group 1-7, respectively. Approximately 180
participants were randomized in a ratio of 4:1; active drug to matching placebo in each
group.

Inclusion Criteria:

- Male or female with confirmed diagnosis of CF

- Must have the F508del-CFTR gene mutation in both alleles (Groups 1, 2, 3, 4, 5, 6).
Group 7 participants must have the F508del-CFTR mutation on 1 allele, and gating
mutation G551D on the second allele and have been on their physician prescribed 150 mg
KalydecoTM q12h (commercially available ivacaftor) for at least 28 days at the
Screening Visit.

- Forced expiratory volume in 1 second(FEV1) 40% to 90% (inclusive) of predicted normal
for age, gender, and height (Knudson standards) at screening

- Weight >40 kg and BMI >18.5

- Participants of child-bearing potential and who are sexually active must meet the
contraception requirements.

Exclusion Criteria:

- History of any illness that, in the opinion of the investigator, might confound the
results of the study or pose an additional risk in administering study drug to the
participant.

- An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in
therapy (including antibiotics) for pulmonary disease within 4 weeks before Study Day
1.

- History of solid organ or hematological transplantation

- Participation in a clinical study involving administration of either an
investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever
is longer) before screening

- History of alcohol, medication, or illicit drug abuse within 1 year prior to screening

- Pregnant, breast-feeding, or not willing to follow contraception requirements