Clinical trial NCT02412111: 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
Official title: A Phase 3, Randomized, Double-Blind, Ivacaftor-Controlled, Parallel-Group 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 and a Second CFTR Allele With a Gating Defect That Is Clinically Demonstrated to be Ivacaftor Responsive
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2015-04-08
Enrollment: 156
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
timeFrame: Baseline, Through Week 8
Secondary outcomes:
measure: Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
timeFrame: Baseline, Through Week 8
measure: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline Through Week 8
timeFrame: Baseline, Through Week 8
measure: Absolute Change From Baseline in Sweat Chloride Through Week 8
timeFrame: Baseline, Through Week 8
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 16
measure: Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
timeFrame: Predose on Week -2 for Run-in period; Pre-dose on Week 2 for Active comparator period
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Oakland
country: United States
state: California
city: San Diego
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Orlando
country: United States
state: Florida
city: Augusta
country: United States
state: Georgia
city: Indianapolis
country: United States
state: Indiana
city: Lexington
country: United States
state: Kentucky
city: Boston
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: Grand Rapids
country: United States
state: Michigan
city: Saint Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Lebanon
country: United States
state: New Hampshire
city: Manchester
country: United States
state: New Hampshire
city: Morristown
country: United States
state: New Jersey
city: New Brunswick
country: United States
state: New Jersey
city: Albany
country: United States
state: New York
city: New York
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Knoxville
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Morgantown
country: United States
state: West Virginia
city: Chermside
country: Australia
city: Clayton
country: Australia
city: Melbourne
country: Australia
city: South Brisbane
country: Australia
city: Westmead
country: Australia
city: Innsbruck
country: Austria
city: Bruxelles
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Calgary
country: Canada
city: Toronto
country: Canada
city: Vancouver
country: Canada
city: Paris Cedex 14
country: France
city: Dresden
country: Germany
city: Erlangen
country: Germany
city: Essen
country: Germany
city: Frankfurt
country: Germany
city: Giessen
country: Germany
city: Heidelberg
country: Germany
city: Jena
country: Germany
city: Munchen
country: Germany
city: Cork
country: Ireland
city: Dublin
country: Ireland
city: Bari
country: Italy
city: Milano
country: Italy
city: Roma
country: Italy
city: Belfast
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Cardiff
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle
country: United Kingdom
city: Southampton
country: United Kingdom
Study officials:
References:
citation: 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.