This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter, crossover study that will evaluate the efficacy of LUM/IVA in subjects with CF 12 years of age and older who have at least one A455E mutation.

Inclusion Criteria:

• Male or female with confirmed diagnosis of CF
• All subjects must have an A455E mutation on at least 1 CFTR allele; no more than 10 subjects may have an F508del mutation on 1 CFTR allele.
• Forced expiratory volume in one second (FEV1) ≥30% of predicted and ≤90% of predicted at the Screening Visit, based on the Global Lung Function Initiative (GLI)-2012 multi ethnic all-age reference equations.
• Stable CF disease as judged by the investigator.
• Willing to remain on a stable medication regimen for CF from 4 weeks before Day 1 through the Follow up Visit.

Exclusion Criteria:

• History of any comorbidity reviewed at the Screening Visit 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.
• A G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or R117H mutation on at least one CFTR allele.
• Pregnant or breastfeeding.
• Any abnormal laboratory values at the Screening Visit.
• History of cataract/lens opacity, or evidence of cataract/lens opacity determined to be clinically significant by the ophthalmologist or optometrist during the ophthalmologic examination at the Screening Visit.
• Use of strong inhibitors or strong inducers of CYP3A, including consumption of certain herbal medications and certain fruit and fruit juices, within 14 days before Day 1
• Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements

Up to Week 28