A Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation

Vertex Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Cystic Fibrosis

Treatments: Drug: Placebo (matched to ivacaftor); Drug: Placebo (matched to VX-661 plus ivacaftor combination); Drug: Ivacaftor; Drug: VX-661 plus ivacaftor combination

Study type: Interventional

Funder types: Industry

Identifiers

NCT02516410

2014-004787-37 (EudraCT Number)

VX14-661-107

Details and patient eligibility

About

Study to evaluate the efficacy of VX-661 in combination with ivacaftor (IVA, VX-770) through Week 12 in participants with cystic fibrosis (CF) who are heterozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene and with a second CFTR mutation that is not likely to respond to VX-661 and/or IVA therapy (F508del/not responsive [NR]).

Enrollment: 168 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Confirmed diagnosis of CF defined as a sweat chloride value greater than or equal to (>=)60 millimole per liter (mmol/L) by quantitative pilocarpine iontophoresis.
• Heterozygous for the F508del-CFTR mutation and with a second CFTR mutation that is not likely to respond to VX-661 and/or ivacaftor therapy, genotype to be confirmed via assessment at the Screening Visit.
• Forced Expiratory Volume in 1 Second (FEV1) >=40 percent (%) and less than or equal to (<=)90% of predicted normal for age, sex, and height at Screening 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 participant.
• An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug).
• History of solid organ or hematological transplantation.
• Ongoing or prior participation in an investigational drug study or use of commercially available CFTR modulator within 30 days of screening.
• Pregnant or nursing females.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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168 participants in 2 patient groups, including a placebo group

VX-661/IVA

Experimental group

Description:

VX-661 100 milligram (mg) plus IVA 150 mg fixed dose combination (FDC) tablet administered orally in the morning and IVA 150 mg film-coated tablet administered orally in the evening up to Week 12.

Treatment:

Drug: Ivacaftor

Drug: VX-661 plus ivacaftor combination

Placebo

Placebo Comparator group

Description:

Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA film-coated tablet administered orally in the evening up to Week 12.

Treatment:

Drug: Placebo (matched to ivacaftor)

Drug: Placebo (matched to VX-661 plus ivacaftor combination)