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Clinical trials identifierNCT02392234
Study codesVX14-661-108, EXPAND
Study titleA Phase 3, Randomized, Double-Blind, Placebo-Controlled, Crossover 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-CFTR Mutation, and a Second Allele With a CFTR Mutation Predicted to Have Residual Function
Drug (brand name)VX-661 (tezacaftor)
Drug administrationTablet taken by mouth
Eligible CF patientsAged 12 Years and older, heterozygous for the F508del-CFTR mutation and with a second CFTR mutation predicted to have residual function
Controlled study?Yes (placebo controlled)
Randomised study?Yes
Blinded study?Yes (double blind - neither medical staff, nor participants knew which treatment participants were taking)
Extension study?No
Study timeframeThe study was conducted between March 2015 and March 2017


What does this mean for me?This study was in people with one F508del mutation, and a second rare “residual function” mutation – these mutations are generally rare and have some CF channel function already. In these people the combination of VX-661 (tezacaftor) with ivacaftor resulted in a 6.8% improvement in lung function as measured by FEV1 percent predicted, compared to the placebo, or “dummy drug” group. There was also an improvement in self-reported quality of life. Safety appears good. Based on the press release, Vertex Pharmaceuticals now plan to apply to the United States Federal Drug Administration and European Medicines Agency to seek a license for this drug combination to be approved for this specific patient group and age range. As yet the specific list of residual function mutations included in this study is not in the public domain. 
Study:This Phase 3 trial was conducted in more than 80 trial sites, mainly in North America and Europe.
Aim:To evaluate the efficacy and safety of tezacaftor/ivacaftor combination treatment as well as ivacaftor monotherapy
Participants:In total, approximately 250 people were enrolled and randomly assigned to one of six treatment groups. There were 75 participants from 21 ECFS-CTN sites in Belgium, France, Germany, Italy, Israel, the Netherlands, Poland and the UK.
Treatment:Patients were randomized to one of six treatment groups to receive tezacaftor/ivacaftor combination therapy (tezacaftor 100 mg once daily plus ivacaftor 150 mg every 12 hours), ivacaftor monotherapy (150 mg every 12 hours) or placebo for eight weeks. Then participants took no study drugs for 8 weeks (called a washout period) before switching to one of the other two treatment regimens for another eight weeks. In the study, approximately 250 people were treated at more than 80 trial sites, mainly in North America and Europe.
Safety:In the EXPAND study, the safety profile observed for the tezacaftor/ivacaftor combination treatment was favorable and similar to that seen in the EVOLVE study. The Tezacaftor/ivacaftor combination treatment as well as ivacaftor monotherapy were both generally well tolerated. The majority of adverse events were mild or moderate. The most common adverse events (≥15%), regardless of treatment group, were cough and infective pulmonary exacerbation.
Efficacy:Participants in the Tezacaftor/ivacaftor combination group had 6.8% better lung function than the placebo group at the end of the study. Patients in the ivacaftor only group had 4.7% better lung function than the placebo group at the end of the study.
Data source:The summary of data provided here is from a registry posting, available here: from a sponsor press release, available here: