A Study Evaluating the Safety and Efficacy of VX-440 Combination Therapy in Subjects With Cystic Fibrosis

Inclusion Criteria:

- Willing and able to comply with scheduled visits, treatment plan, study restrictions,
laboratory tests, contraceptive guidelines, and other study procedures.

- To prevent pregnancy, female participants of childbearing potential and their male
partners will be required to use pre-specified, highly effective methods of
non-hormonal contraception. Male participants with female partners of childbearing
potential will be required to use a condom.

- Body weight ≥35 kg.

- Sweat chloride value ≥60 mmol/L from test results obtained during screening.

- Subjects must have an eligible CFTR genotype:

- Heterozygous for F508del and a minimal function (MF) mutation known or predicted
not to be responsive to TEZ and/or IVA.

- Homozygous for F508del

- Subjects must have an FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height
at the Screening Visit

- Stable CF disease as judged by the investigator.

- Willing to remain on a stable CF medication regimen through the planned end of
treatment or, if applicable, the Safety Follow up Visit.

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 in administering study drug to the
subject.

- History of cirrhosis with portal hypertension.

- Risk factors for Torsade de Pointes

- History of hemolysis.

- Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.

- Clinically significant abnormal laboratory values at screening

- An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in
therapy for pulmonary disease within 28 days before the first dose of study drug.

- Lung infection with organisms associated with a more rapid decline in pulmonary status

- An acute illness not related to CF within 14 days before the first dose of study drug

- A standard digital ECG demonstrating QTc >450 msec at screening.

- History of solid organ or hematological transplantation.

- History or evidence of cataract or lens opacity determined to be clinically
significant by the ophthalmologist or optometrist based on the ophthalmologic
examination during the Screening Period.

- History of alcohol or drug abuse in the past year, including but not limited to,
cannabis, cocaine, and opiates, as deemed by the investigator.

- Ongoing or prior participation in an investigational drug study, with certain
exceptions. (e.g., ongoing participation in NCT02565914)

- Use of commercially available CFTR modulator (e.g., Kalydeco, Orkambi) within 14 days
before screening (applies only to the Heterozygous F508del/MF cohorts; does not apply
to the Homozygous F508del/F508del Cohort).

- Pregnant or nursing females: Females of childbearing potential must have a negative
pregnancy test at screening and Day 1.