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

Vertex Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Cystic Fibrosis

Treatments: Drug: Ivacaftor; Drug: Placebo matched to VX-661/ ivacaftor; Drug: Placebo matched to Ivacaftor; Drug: VX-661/Ivacaftor

Study type: Interventional

Funder types: Industry

Identifiers

NCT02392234

VX14-661-108

2014-004788-18 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 248 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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248 participants in 3 patient groups, including a placebo group

VX-661/Ivacaftor combination

Experimental group

Treatment:

Drug: VX-661/Ivacaftor

Drug: Ivacaftor

Drug: Placebo matched to Ivacaftor

Ivacaftor monotherapy

Experimental group

Treatment:

Drug: Placebo matched to VX-661/ ivacaftor

Drug: Ivacaftor

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo matched to VX-661/ ivacaftor

Drug: Placebo matched to Ivacaftor