This is a Phase 3, 2-arm, multicenter study with an open-label ivacaftor arm and an observational arm to evaluate the safety and efficacy of long-term ivacaftor treatment in participants with cystic fibrosis (CF) who are <24 months of age at treatment initiation and have an approved Ivacaftor-Responsive mutation.

Inclusion Criteria:

Ivacaftor Arm: Participants From Study 124 (NCT02725567 ) Part B:

• Participants transitioning from Study 124 Part B must have completed the last study visit of Study 124 Part B.
• As judged by the investigator, parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions; and must sign the informed consent form (ICF).

Ivacaftor Arm: Participants Not From Study 124 Part B:

• Confirmed diagnosis of CF, or 2 CF-causing mutations.
• An ivacaftor- responsive CFTR mutation on at least 1 allele. Participants will be eligible in countries/regions where ivacaftor is approved for use in participants 2 years of age and older.
• As judged by the investigator, parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions; and must sign the ICF.

Observational Arm:

• Received ivacaftor treatment in Study 124 Part B and elected not to enroll or ineligible to enroll in the ivacaftor arm of Study 126.

Exclusion Criteria:

Ivacaftor Arm: Participants From Study 124 Part B:

• History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering ivacaftor to the participant.
• Participants receiving commercially available ivacaftor treatment

Ivacaftor Arm: Participants Not From Study 124 Part B:

• History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering ivacaftor to the participant
• An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks of Day 1
• Abnormal liver function at screening
• Hemoglobin <9.5 g/dL at screening
• History of solid organ or hematological transplantation
• Use of any moderate or strong inducers or inhibitors of CYP3A within 2 weeks of Day 1

Observational Arm:

• Receiving ivacaftor treatment

Other protocol defined Inclusion/Exclusion criteria may apply.

Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing