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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,131
- 主要终点
- Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 NCT
- •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 NCT
- •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
- •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 NCT
- •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 NCT
- •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 NCT
- •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.
- •Participants who meet all of the following inclusion criteria will be eligible for Part C.
- •Did not withdraw consent from Part B of Study NCT
- •Completed study drug treatment during Part B of NCT
- •Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit of Part C.
排除标准
- •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.
研究组 & 干预措施
TEZ/IVA
Part A: Participants who received either TEZ/IVA, IVA monotherapy or Placebo in parent studies 103,106,107,108,109 and 111 were administered TEZ 100 milligram (mg)/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks.
Part B: Participants who received either TEZ/IVA, IVA monotherapy or Placebo in parent studies 106,108,109,112 and 114 were administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks.
Part C: Participants who received TEZ/IVA, IVA monotherapy or Placebo in parent studies 106,108, and 114 were administered TEZ 100 mg/IVA 150 mg fixed dose tablet in the morning and IVA 150 mg mono tablet in the evening for 192 weeks.
干预措施: TEZ/IVA (Drug)
TEZ/IVA
Part A: Participants who received either TEZ/IVA, IVA monotherapy or Placebo in parent studies 103,106,107,108,109 and 111 were administered TEZ 100 milligram (mg)/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks.
Part B: Participants who received either TEZ/IVA, IVA monotherapy or Placebo in parent studies 106,108,109,112 and 114 were administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks.
Part C: Participants who received TEZ/IVA, IVA monotherapy or Placebo in parent studies 106,108, and 114 were administered TEZ 100 mg/IVA 150 mg fixed dose tablet in the morning and IVA 150 mg mono tablet in the evening for 192 weeks.
干预措施: IVA (Drug)
结局指标
主要结局
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Day 1 up to Week 100
Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs
时间窗: Day 1 up to Week 100
Part C: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Day 1 up to Week 196
次要结局
- Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Number of Pulmonary Exacerbation (PEx) Events for 108/110 PEx Analysis Set(From Baseline up to Week 96)
- Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 108/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Number of Pulmonary Exacerbation (PEx) Events for 106/110 PEx Analysis Set(From Baseline up to Study 110 Week 96)
- Part A: Absolute Change in Body Mass Index (BMI) for 106/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Absolute Change in Body Mass Index (BMI) for 103/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Absolute Change in Body Mass Index (BMI) for Study 111/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Absolute Change in BMI Z-score for 106/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Absolute Change in Body Mass Index (BMI) for 108/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Absolute Change in BMI Z-score for 108/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Plasma Concentrations of TEZ, TEZ Metabolite (M1-TEZ), Ivacaftor (IVA) and Ivacaftor Metabolite (M1-IVA)(Week 24)
- Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)(From Baseline at Study 110 Week 96)
- Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 106/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Absolute Change in Body Weight for 103/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Time-to-first Pulmonary Exacerbation (PEx) for 108/110 PEx Analysis Set(96 weeks)
- Part A: Absolute Change in Body Weight for Study 106/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Absolute Change in Body Weight for 108/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Absolute Change in Height Z-score for 106/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Time-to-first Pulmonary Exacerbation (PEx) for 106/110 PEx Analysis Set(96 weeks)
- Part A: Absolute Change in Body Weight for 111/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Absolute Change in Body Weight Z-score for 106/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Absolute Change in Body Weight Z-score for 108/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part A: Absolute Change in Height Z-score for 108/110 Efficacy Set(From Baseline at Study 110 Week 96)
- Part B: Number of Pulmonary Exacerbation (PEx) Events(From Baseline up to Week 96)
- Part B: Absolute Change in Body Mass Index (BMI)(From Baseline at Week 96)
- Part B: Absolute Change in BMI Z-score(From Baseline at Week 96)