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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02412111




Registration number
NCT02412111
Ethics application status
Date submitted
3/04/2015
Date registered
8/04/2015
Date last updated
8/01/2019

Titles & IDs
Public 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
Scientific 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
Secondary ID [1] 0 0
VX14-661-109
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Ivacaftor (Run-in Period) - Ivacaftor 150 milligram (mg) tablet orally every 12 hours for 4 weeks.

Experimental: VX-661 + Ivacaftor (Active comparator period) - 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.

Active comparator: Ivacaftor monotherapy (Active comparator period) - Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
Timepoint [1] 0 0
Baseline, Through Week 8
Secondary outcome [1] 0 0
Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
Timepoint [1] 0 0
Baseline, Through Week 8
Secondary outcome [2] 0 0
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline Through Week 8
Timepoint [2] 0 0
Baseline, Through Week 8
Secondary outcome [3] 0 0
Absolute Change From Baseline in Sweat Chloride Through Week 8
Timepoint [3] 0 0
Baseline, Through Week 8
Secondary outcome [4] 0 0
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [4] 0 0
Baseline up to Week 16
Secondary outcome [5] 0 0
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
Timepoint [5] 0 0
Predose on Week -2 for Run-in period; Pre-dose on Week 2 for Active comparator period

Eligibility
Key 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.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2017
Sample size
Target
Accrual to date
Final
156
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Chermside
Recruitment hospital [2] 0 0
- Clayton
Recruitment hospital [3] 0 0
- Melbourne
Recruitment hospital [4] 0 0
- South Brisbane
Recruitment hospital [5] 0 0
- Westmead
Recruitment postcode(s) [1] 0 0
- Chermside
Recruitment postcode(s) [2] 0 0
- Clayton
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
- South Brisbane
Recruitment postcode(s) [5] 0 0
- Westmead
Recruitment outside Australia
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United States of America
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Alabama
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California
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Colorado
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District of Columbia
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Florida
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Michigan
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Bruxelles
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Gent
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Leuven
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Calgary
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Toronto
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Vancouver
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France
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Paris Cedex 14
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Germany
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Dresden
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Germany
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Erlangen
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Essen
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Germany
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Frankfurt
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Germany
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Giessen
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Germany
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Heidelberg
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Bari
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Roma
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Vertex Pharmaceuticals Incorporated
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02412111
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
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Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02412111