Clinical trial NCT02565914: A Study to Evaluate the Safety and Efficacy of Long Term Treatment With VX-661 in Combination With Ivacaftor in Participants With Cystic Fibrosis Who Have an F508del-CFTR Mutation
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2015-10-01
Enrollment: 1131
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 3, multicenter, open-label, 3-part rollover study in subjects with CF who are homozygous or heterozygous for the F508del-CFTR mutation and who participated in studies VX13-661-103 (Study 103, NCT02070744), VX14-661-106 (Study 106, NCT02347657), VX14-661-107 (Study 107, NCT02516410), VX14-661-108 (Study 108, NCT02392234), VX14-661-109 (Study 109, NCT02412111), VX14-661-111 (Study 111, NCT02508207), VX15-661-112 (NCT02730208), and VX16-661-114 (NCT03150719). The study is designed to evaluate the safety and efficacy of long-term treatment of VX-661 in combination with ivacaftor.


Eligibility criteria: Inclusion Criteria:

Part A:

* Participants 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 participants from NCT02508207.
* Willing to remain on a stable CF regimen through the Safety Follow-up Visit.
* Participants 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.
* Participants 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 participants from NCT02508207), but do not meet eligibility criteria for enrollment into the Treatment Cohort

Part B:

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

Participants 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 participants 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.

Part C:

* Participants who meet all of the following inclusion criteria will be eligible for Part C.
* Did not withdraw consent from Part B of Study NCT02565914.
* Completed study drug treatment during Part B of NCT02565914.
* Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit of Part C.

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.

Primary outcomes:
measure: Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Week 100
measure: Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs
timeFrame: Day 1 up to Week 100
measure: Part C: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Week 196
Secondary outcomes:
measure: Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Number of Pulmonary Exacerbation (PEx) Events for 106/110 PEx Analysis Set
timeFrame: From Baseline up to Study 110 Week 96
measure: Part A: Number of Pulmonary Exacerbation (PEx) Events for 108/110 PEx Analysis Set
timeFrame: From Baseline up to Week 96
measure: Part A: Absolute Change in Body Mass Index (BMI) for 106/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change in Body Mass Index (BMI) for 108/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change in Body Mass Index (BMI) for 103/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change in Body Mass Index (BMI) for Study 111/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change in BMI Z-score for 106/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change in BMI Z-score for 108/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 106/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 108/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change in Body Weight for Study 106/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change in Body Weight for 108/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change in Body Weight for 103/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change in Body Weight for 111/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change in Body Weight Z-score for 106/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change in Body Weight Z-score for 108/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change in Height Z-score for 106/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Absolute Change in Height Z-score for 108/110 Efficacy Set
timeFrame: From Baseline at Study 110 Week 96
measure: Part A: Time-to-first Pulmonary Exacerbation (PEx) for 106/110 PEx Analysis Set
timeFrame: 96 weeks
measure: Part A: Time-to-first Pulmonary Exacerbation (PEx) for 108/110 PEx Analysis Set
timeFrame: 96 weeks
measure: Part A: Plasma Concentrations of TEZ, TEZ Metabolite (M1-TEZ), Ivacaftor (IVA) and Ivacaftor Metabolite (M1-IVA)
timeFrame: Week 24
measure: Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
timeFrame: From Baseline at Study 110 Week 96
measure: Part B: Absolute Change in Body Mass Index (BMI)
timeFrame: From Baseline at Week 96
measure: Part B: Absolute Change in BMI Z-score
timeFrame: From Baseline at Week 96
measure: Part B: Number of Pulmonary Exacerbation (PEx) Events
timeFrame: From Baseline up to Week 96
Other outcomes:
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city: Bron Cedex
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city: Lille
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city: Marseilles
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city: Montpellier Cedex 5
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city: Paris Cedex 14
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city: Rouen Cedex
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city: Berlin
country: Germany
city: Bochum
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city: Ancona
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city: Genova
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country: Italy
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country: Italy
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country: Netherlands
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country: Spain
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country: Spain
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country: Sweden
city: Stockholm
country: Sweden
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country: Sweden
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country: Switzerland
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state: West Yorkshire
city: Belfast
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country: United Kingdom
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city: Stoke-on-Trent
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Study officials:
References:
citation: Flume PA, Biner RF, Downey DG, Brown C, Jain M, Fischer R, De Boeck K, Sawicki GS, Chang P, Paz-Diaz H, Rubin JL, Yang Y, Hu X, Pasta DJ, Millar SJ, Campbell D, Wang X, Ahluwalia N, Owen CA, Wainwright CE; VX14-661-110 study group. Long-term safety and efficacy of tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years or older who are homozygous or heterozygous for Phe508del CFTR (EXTEND): an open-label extension study. Lancet Respir Med. 2021 Jul;9(7):733-746. doi: 10.1016/S2213-2600(20)30510-5. Epub 2021 Feb 10.