Back to resultsA 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
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ivacaftor
Tezacaftor/Ivacaftor
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Ivacaftor (Run-in Period)
VX-661 + Ivacaftor (Active comparator period)
Ivacaftor monotherapy (Active comparator period)
Arm Description
Ivacaftor 150 milligram (mg) tablet orally every 12 hours for 4 weeks.
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.
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
Outcomes
Primary Outcome Measures
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Secondary Outcome Measures
Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline Through Week 8
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Absolute Change From Baseline in Sweat Chloride Through Week 8
Sweat samples were collected using an approved collection device.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
Full Information
NCT ID
NCT02412111
First Posted
April 3, 2015
Last Updated
January 7, 2019
Sponsor
Vertex Pharmaceuticals Incorporated
1. Study Identification
Unique Protocol Identification Number
NCT02412111
Brief Title
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
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
June 2015 (Actual)
Primary Completion Date
September 2017 (Actual)
Study Completion Date
September 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
156 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ivacaftor (Run-in Period)
Arm Type
Experimental
Arm Description
Ivacaftor 150 milligram (mg) tablet orally every 12 hours for 4 weeks.
Arm Title
VX-661 + Ivacaftor (Active comparator period)
Arm Type
Experimental
Arm 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.
Arm Title
Ivacaftor monotherapy (Active comparator period)
Arm Type
Active Comparator
Arm Description
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Ivacaftor
Other Intervention Name(s)
VX-770
Intervention Type
Drug
Intervention Name(s)
Tezacaftor/Ivacaftor
Other Intervention Name(s)
VX-661/VX-770
Primary Outcome Measure Information:
Title
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame
Baseline, Through Week 8
Secondary Outcome Measure Information:
Title
Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame
Baseline, Through Week 8
Title
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline Through Week 8
Description
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time Frame
Baseline, Through Week 8
Title
Absolute Change From Baseline in Sweat Chloride Through Week 8
Description
Sweat samples were collected using an approved collection device.
Time Frame
Baseline, Through Week 8
Title
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
Baseline up to Week 16
Title
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
Time Frame
Predose on Week -2 for Run-in period; Pre-dose on Week 2 for Active comparator period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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
Facility Information:
City
Birmingham
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Alabama
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United States
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Oakland
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San Diego
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Chermside
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Australia
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Clayton
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Australia
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Westmead
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Innsbruck
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Austria
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Bruxelles
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Gent
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London
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Manchester
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Newcastle
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Southampton
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United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
33339768
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.
Results Reference
derived
Learn more about this trial
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
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