A Phase 3 Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation

Phase 3

Completed

Interventions: Drug: VX-661/Ivacaftor
Drug: Ivacaftor
Drug: Placebo matched to VX-661/ ivacaftor
Drug: Placebo matched to Ivacaftor

Brief Summary: The purpose of this study is to evaluate the efficacy and safety of VX-661 in combination with ivacaftor (IVA, VX-770) and IVA monotherapy in participants with Cystic Fibrosis (CF) who are heterozygous for F508del-CFTR allele and a second allele with a CFTR mutation predicted to have residual function.

Recruitment & Eligibility

Inclusion Criteria

Heterozygous for F508del-CFTR and a second allele with a CFTR mutation predicted to have residual function
Forced Expiratory Volume in 1 Second (FEV1) greater than or equal to (≥) 40 percent (%) and less than or equal to (≤) 90% of predicted normal for age, sex, and height during screening
Sweat chloride value ≥60 millimole per liter (mmol/L) during screening OR as documented in the participant's medical record
Stable CF disease as judged by the investigator

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 participant
An acute upper or lower respiratory infection, pulmonary exacerbation
History of solid organ or hematological transplantation
Ongoing or prior participation in an investigational drug study (including studies investigating VX-661, lumacaftor [VX-809], and/or ivacaftor) within 30 days of screening
Pregnant and nursing females
Sexually active participants of reproductive potential who are not willing to follow the contraception requirements

Arm && Interventions

Group	Intervention	Description
VX-661/Ivacaftor combination	VX-661/Ivacaftor	-
VX-661/Ivacaftor combination	Placebo matched to Ivacaftor	-
Ivacaftor monotherapy	Placebo matched to VX-661/ ivacaftor	-
Placebo	Placebo matched to VX-661/ ivacaftor	-
Placebo	Placebo matched to Ivacaftor	-
Ivacaftor monotherapy	Ivacaftor	-
VX-661/Ivacaftor combination	Ivacaftor	-

Primary Outcome Measures

Name	Time	Method
Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Week 4 and Week 8	Baseline, Week 4 and Week 8 of each treatment period	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Secondary Outcome Measures

Name	Time	Method
Absolute Change From Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Week 4 and Week 8	Baseline, Week 4 and Week 8 of each treatment period	The CFQ-R assessed respiratory symptoms on a scale with scores ranging from 0 to 100; where higher scores indicated fewer symptoms and better health-related quality of life.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Day 1 up to Week 28
Relative Change From Study Baseline in ppFEV1 at Average of Week 4 and Week 8	Baseline, Week 4 and Week 8 of each treatment period	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change From Study Baseline in Sweat Chloride at Average of Week 4 and Week 8	Baseline, Week 4 and Week 8 of each treatment period
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661), IVA and IVA Metabolite (M1 IVA) After Administration of VX-661/IVA Combination Therapy	Pre-morning dose on Week 8 of each treatment period
Ctrough of IVA and IVA Metabolite (M1 IVA) After Administration of IVA Monotherapy	Pre-morning dose on Week 8 of each treatment period