A Phase 3 Study of Tezacaftor (VX-661) in Combination With Ivacaftor (VX-770) in Subjects Aged 12 Years and Older With Cystic Fibrosis (CF), Who Have One F508del-CFTR Mutation and a Second Mutation That Has Been Demonstrated to be Clinically Responsive to Ivacaftor

Vertex Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Cystic Fibrosis

Treatments: Drug: Ivacaftor; Drug: Tezacaftor/Ivacaftor

Study type: Interventional

Funder types: Industry

Identifiers

NCT02412111

VX14-661-109

Details and patient eligibility

About

This is a Phase 3, randomized, double-blind, ivacaftor-controlled, parallel-group, multicenter study of tezacaftor in combination with ivacaftor in subjects aged 12 years and older with CF who are heterozygous for the F508del-CFTR mutation and a second CFTR allele with a gating defect that is clinically demonstrated to be ivacaftor responsive.

Enrollment: 156 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Heterozygous for F508del-CFTR mutation and a second CFTR allele with a gating defect that is clinically demonstrated to be ivacaftor responsive
• FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height during screening
• 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 subject.
• Pregnant and nursing females (females of childbearing potential must have a negative pregnancy test at Screening and Week -4 Visits).
• Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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156 participants in 3 patient groups

Ivacaftor (Run-in Period)

Experimental group

Description:

Ivacaftor 150 milligram (mg) tablet orally every 12 hours for 4 weeks.

Treatment:

Drug: Ivacaftor

VX-661 + Ivacaftor (Active comparator period)

Experimental group

Description:

VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks.

Treatment:

Drug: Tezacaftor/Ivacaftor

Drug: Ivacaftor

Ivacaftor monotherapy (Active comparator period)

Active Comparator group

Description:

Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.

Treatment:

Drug: Ivacaftor