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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02565914




Registration number
NCT02565914
Ethics application status
Date submitted
18/09/2015
Date registered
1/10/2015
Date last updated
22/11/2018

Titles & IDs
Public title
A Study to Evaluate the Safety and Efficacy of Long Term Treatment With VX-661 in Combination With Ivacaftor in Subjects With Cystic Fibrosis Who Have an F508del-CFTR Mutation
Scientific title
A Phase 3, Open-label, Rollover Study to Evaluate the Safety and Efficacy of Long Term Treatment With VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation
Secondary ID [1] 0 0
2014-004827-29
Secondary ID [2] 0 0
VX14-661-110
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
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
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

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - VX-661/ivacaftor
Treatment: Drugs - ivacaftor

Experimental: Part A Treatment Cohort: VX-661/ivacaftor - VX-661 100 mg/ ivacaftor 150 mg fixed dose combination (FDC) tablet daily (qd) in the morning and ivacaftor 150 mg tablet qd in the evening

No Intervention: Part A Observational Cohort - Long-term Follow-up

Experimental: Part B Treatment: VX-661/ivacaftor - VX-661 100 mg/ ivacaftor 150 mg fixed dose combination (FDC) tablet daily (qd) in the morning and ivacaftor 150 mg tablet qd in the evening


Treatment: Drugs: VX-661/ivacaftor


Treatment: Drugs: ivacaftor


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A: Safety and tolerability of long-term treatment of VX-661 in combination with ivacaftor based on adverse events (AEs), ophthalmologic exams, clinical laboratory values, standard digital electrocardiograms (ECGs), vital signs, and pulse oximetry
Timepoint [1] 0 0
from baseline through Study Completion (up to 3 years)
Secondary outcome [1] 0 0
Parts A and B: Absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1)
Timepoint [1] 0 0
from baseline through Week 96
Secondary outcome [2] 0 0
Part A: Relative change from baseline in ppFEV1
Timepoint [2] 0 0
from baseline through Week 96
Secondary outcome [3] 0 0
Parts A and B: Number of pulmonary exacerbations
Timepoint [3] 0 0
from baseline through Week 96
Secondary outcome [4] 0 0
Parts A and B: Absolute change from baseline in body mass index (BMI)
Timepoint [4] 0 0
from baseline through Week 96
Secondary outcome [5] 0 0
Parts A and B: Absolute change from baseline in BMI z-score for subjects aged <20 years
Timepoint [5] 0 0
from baseline through Week 96
Secondary outcome [6] 0 0
Part A: Absolute change from baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score
Timepoint [6] 0 0
from baseline through Week 96
Secondary outcome [7] 0 0
Part A: Absolute change from baseline in body weight
Timepoint [7] 0 0
from baseline through Week 96
Secondary outcome [8] 0 0
Part A: Absolute change from baseline in body weight z-score for subjects aged <20 years
Timepoint [8] 0 0
from baseline through Week 96
Secondary outcome [9] 0 0
Part A: Absolute change from baseline in height z-score for subjects aged <20 years
Timepoint [9] 0 0
from baseline through Week 96
Secondary outcome [10] 0 0
Part A: Time-to-first pulmonary exacerbation
Timepoint [10] 0 0
from baseline through Week 96
Secondary outcome [11] 0 0
Part A: Pharmacokinetic (PK) parameters: trough concentrations of VX-661 , a VX-661 metabolite (M1-661), ivacaftor, ivacaftor metabolite (M1-ivacaftor)
Timepoint [11] 0 0
from baseline through Week 96
Secondary outcome [12] 0 0
Part A: Observational Cohort: Safety, as determined by related serious adverse events (SAEs)
Timepoint [12] 0 0
from baseline through study Completion (up to 3 years)
Secondary outcome [13] 0 0
Part B: Safety and tolerability assessments including number of subjects with adverse events (AEs) and serious adverse events
Timepoint [13] 0 0
from baseline through safety follow-up visit

Eligibility
Key inclusion criteria
Part A:

- Subjects entering the Treatment Cohort must meet all of the following criteria:

- Elect to enroll in the Treatment Cohort

- Completed study drug Treatment Period in a parent study (NCT02070744, NCT02347657,
NCT02516410, NCT02392234, NCT02412111) or study drug treatment and the Safety Follow
up Visit for subjects from NCT02508207.

- Willing to remain on a stable CF regimen through the Safety Follow-up Visit.

- Subjects re-enrolling in the Part A Treatment Cohort must meet all of the following
criteria:

- Previously received at least 4 weeks of study drug before discontinuing in Part A
of Study NCT02565914 to participate in another qualified Vertex study.

- Completed the last required visit of another qualified Vertex study before or
during the Returning Visit in Part A Study NCT02565914.

- Subjects entering the Part A Observational Cohort must meet the following criteria:

- <18 years of age (age on the date of informed consent/assent in the parent study)

- Completed study drug Treatment Period in a parent study or study drug treatment
and the Safety Follow up Visit for subjects from NCT02508207, but do not elect to
enroll in the NCT02565914 Treatment Cohort; or

- Received at least 4 weeks of study drug treatment and completed visits up to the
last scheduled visit of the Treatment Period of a parent study (and the Safety
Follow up Visit for subjects from NCT02508207), but do not meet eligibility
criteria for enrollment into the Treatment Cohort

Part B:

Part B Subjects who meet all of the following inclusion criteria will be eligible for Part
B.

- Did not withdraw consent from the parent study or Part A of Study NCT02565914.

- Completed study drug treatment during the Treatment Period in Part A of NCT02565914,
Studies NCT02730208 or NCT03150719, or other eligible Vertex studies.

- Willing to remain on a stable CF medication (and supplement) regimen through the 96
week visit of Study NCT02565914.

Subjects re enrolling in Part B must meet all of the following criteria:

- Previously received at least 4 weeks of study drug before discontinuing Study
NCT02565914 to participate in another qualified Vertex study, which is defined as a
Vertex study of investigational CFTR modulators that allows participation of subjects
in Study NCT02565914.

- Completed the last required visit of another qualified Vertex study before or during
the Returning Visit in Part B.

- Willing to remain on a stable CF medication (and supplement) regimen through the 96
week visit in Part B.
Minimum age
12 Years
Maximum age
No limit
Gender
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 to the subject.

- Pregnant and nursing females.

- Sexually active subjects of reproductive potential who are not willing to follow the
contraception requirements.

- History of drug intolerance in the parent study that would pose an additional risk to
the subject.

- Participation in an investigational drug trial (including studies investigating
VX-661/ivacaftor or lumacaftor/ivacaftor) other than the parent studies of NCT02565914
or other eligible Vertex studies investigating VX-661 in combination with ivacaftor,
or use of a commercially available CFTR modulator.

Other protocol defined Inclusion/Exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
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- Chermside
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- Melbourne
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- South Brisbane
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- Westmead
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- Chermside
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- Melbourne
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- South Brisbane
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- Westmead
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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, multicenter, open-label, 2-part rollover study in subjects with CF who are
homozygous or heterozygous for the F508del-CFTR mutation and who participated in Studies
NCT02070744, NCT02347657, NCT02516410, NCT02392234, NCT02412111, and NCT02508207. The study
is designed to evaluate the safety and efficacy of long term treatment of VX-661 in
combination with ivacaftor.
Trial website
https://clinicaltrials.gov/show/NCT02565914
Trial related presentations / publications
Public notes

Contacts
Principal investigator
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Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02565914