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

Summary

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.

Timeline

Start

2015-06

Primary completion

2017-09

Completion

2017-09

Outcome

Sources disagree · no verdict is set; each source's reading is shown below

registry analysis (superiority test); VX-661 + Ivacaftor (Active Comparator Period) vs Ivacaftor Monotherapy (Active Comparator Period); p = 0.5846; Least Square (LS) mean difference 0.3 (95% CI -0.8 to 1.4); Mixed Model for Repeated Measures (MMRM) reads as missed primary endpoint NCT02412111 ↗

paper No significant differences in ppFEV1 or any key secondary endpoint were observed between the IVA and TEZ/IVA groups. reads as missed primary endpoint PMID 33339768 ↗

release “The EXPAND study met its primary endpoint of absolute improvement in lung function” reads as met primary endpoint vrtx.com ↗

release “change in ppFEV1 compared to placebo of 4.0 percentage points (P<0.0001) and 6.8 percentage points (P<0.0001) in EVOLVE and EXPAND respectively.” reads as met primary endpoint vrtx.com ↗

Publications

• McKone EF, DiMango EA, Sutharsan S, Barto TL, Campbell D, Ahluwalia N, Higgins M, Owen CA, Tullis E. A phase 3, randomized, double-blind, parallel-group study to evaluate tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for F508del-CFTR and a gating mutation. J Cyst Fibros. 2021 Mar;20(2):234-242. doi: 10.1016/j.jcf.2020.11.003. Epub 2020 Dec 16.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Ivacaftor	Other / unclassified	150 mg	Oral
Subject	Tezacaftor/Ivacaftor	Unknown	100 mg	Oral
Subject	Tezacaftor/Ivacaftor	Unknown	150 mg	Oral

Indications