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

• ClinicalTrials.gov Identifier: NCT02565914
• Recruitment Status: Completed
• First Posted: October 1, 2015
• Results First Posted: June 16, 2020
• Last Update Posted: January 9, 2023
• Sponsor: Vertex Pharmaceuticals Incorporated
• Information provided by (Responsible Party): Vertex Pharmaceuticals Incorporated

Study Description

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), and VX14-661-111 (Study 111, NCT02508207). The study is designed to evaluate the safety and efficacy of long-term treatment of VX-661 in combination with ivacaftor.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: TEZ/IVA; Drug: IVA	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1044 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: August 2015
• Actual Primary Completion Date: May 2019
• Actual Study Completion Date: December 5, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part A: TEZ/IVA; TEZ 100 mg/IVA150 mg fixed dose tablet once daily in the morning and IVA150 mg mono tablet once daily in the evening.	Drug: TEZ/IVA; Other Names: VX-661/VX-770; tezacaftor/ivacaftor; Drug: IVA; Other Names: VX-770; ivacaftor
Experimental: Part B: TEZ/IVA; TEZ 100 mg/IVA150 mg fixed dose tablet once daily in the morning and IVA150 mg mono tablet once daily in the evening.	Drug: TEZ/IVA; Other Names: VX-661/VX-770; tezacaftor/ivacaftor; Drug: IVA; Other Names: VX-770; ivacaftor
Experimental: Part C: TEZ/IVA; TEZ 100 mg/IVA150 mg fixed dose tablet once daily in the morning and IVA150 mg mono tablet once daily in the evening.	Drug: TEZ/IVA; Other Names: VX-661/VX-770; tezacaftor/ivacaftor; Drug: IVA; Other Names: VX-770; ivacaftor

Outcome Measures

Primary Outcome Measures :

1. Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 up to Week 100 ]

Secondary Outcome Measures :

1. Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
2. Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
3. Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline.
4. Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 111 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 111 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
5. Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
6. Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
7. Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline.
8. Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 111 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 111 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
9. Part A: Number of Pulmonary Exacerbation (PEx) Events for 106/110 PEx Analysis Set [ Time Frame: From Baseline up to Study 110 Week 96 ]
   Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
10. Part A: Number of Pulmonary Exacerbation (PEx) Events for 108/110 PEx Analysis Set [ Time Frame: From Baseline up to Week 96 ]
    Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
11. Part A: Absolute Change in Body Mass Index (BMI) for 106/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
    BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2). Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
12. Part A: Absolute Change in Body Mass Index (BMI) for 108/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
    BMI was defined as weight in kg divided by height in square meter (m^2). Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
13. Part A: Absolute Change in Body Mass Index (BMI) for 103/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
    BMI was defined as weight in kg divided by height in square meter (m^2). Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline.
14. Part A: Absolute Change in Body Mass Index (BMI) for Study 111/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
    BMI was defined as weight in kg divided by height in square meter (m^2). Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 111 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 111 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
15. Part A: Absolute Change in BMI Z-score for 106/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
    The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
16. Part A: Absolute Change in BMI Z-score for 108/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
    The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
17. Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 106/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
    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. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
18. Part A: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 108/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
    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. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
19. Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
    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. Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline.
20. Part A: Absolute Change in Body Weight for Study 106/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
    Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
21. Part A: Absolute Change in Body Weight for 108/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
    Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
22. Part A: Absolute Change in Body Weight for 103/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
    Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline.
23. Part A: Absolute Change in Body Weight for 111/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
    Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 111 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 111 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
24. Part A: Absolute Change in Body Weight Z-score for 106/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
    The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
25. Part A: Absolute Change in Body Weight Z-score for 108/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
    The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
26. Part A: Absolute Change in Height Z-score for 106/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
    The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
27. Part A: Absolute Change in Height Z-score for 108/110 Efficacy Set [ Time Frame: From Baseline at Study 110 Week 96 ]
    The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
28. Part A: Time-to-first Pulmonary Exacerbation (PEx) for 106/110 PEx Analysis Set [ Time Frame: 96 weeks ]
    Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan.
29. Part A: Time-to-first Pulmonary Exacerbation (PEx) for 108/110 PEx Analysis Set [ Time Frame: 96 weeks ]
    Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan.
30. Part A: Plasma Concentrations of TEZ, TEZ Metabolite (M1-TEZ), Ivacaftor (IVA) and Ivacaftor Metabolite (M1-IVA) [ Time Frame: Week 24 ]

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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:

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 - 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.

Part C:

• Subjects 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.

Contacts and Locations

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Ireland

Cork, Ireland

Dublin 4, Ireland

Dublin, Ireland

Limerick, Ireland

Israel

Haifa, NAP, Israel

Haifa, Israel

Jerusalem, Israel

Petah Tikva, Israel

Tel Hashomer, Israel

Italy

Ancona, Italy

Genova, Italy

Milano, Italy

Orbassano, Italy

Palermo, Italy

Potenza, Italy

Roma, Italy

Rome, Italy

Torino, Italy

Verona, Italy

Netherlands

Amsterdam, Netherlands

Den Haag, Netherlands

Heidelberglaan, Netherlands

Nijmegen, Netherlands

Rotterdam, Netherlands

Spain

Barcelona, Spain

Madrid, Spain

Sabadell, Spain

Sevilla, Spain

Valencia, Spain

Sweden

Goteborg, Sweden

Stockholm, Sweden

Uppsala, Sweden

Switzerland

Bern, Switzerland

Zurich, Switzerland

United Kingdom

Leeds, West Yorkshire, United Kingdom

Belfast, United Kingdom

Birmingham, United Kingdom

Exeter, United Kingdom

Glasgow, United Kingdom

Leeds, United Kingdom

Liverpool, United Kingdom

London, United Kingdom

Manchester, United Kingdom

Newcastle Upon Tyne, United Kingdom

Penarth, United Kingdom

Sheffield, United Kingdom

Southampton, United Kingdom

Stoke-on-Trent, United Kingdom

Sponsors and Collaborators

Vertex Pharmaceuticals Incorporated

  Study Documents (Full-Text)

Documents provided by Vertex Pharmaceuticals Incorporated:

Study Protocol  [PDF] June 9, 2017

Statistical Analysis Plan  [PDF] March 20, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Erratum In: Lancet Respir Med. 2021 Apr;9(4):e38.

• Responsible Party: Vertex Pharmaceuticals Incorporated
• ClinicalTrials.gov Identifier: NCT02565914
• Other Study ID Numbers: VX14-661-110; 2014-004827-29 ( EudraCT Number )
• First Posted: October 1, 2015
• Results First Posted: June 16, 2020
• Last Update Posted: January 9, 2023
• Last Verified: January 2023

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Ivacaftor; Chloride Channel Agonists; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action