A Phase 3, Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Lumacaftor in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation
Overview
- Phase
- Phase 3
- Intervention
- Lumacaftor Plus Ivacaftor Combination
- Conditions
- Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation
- Sponsor
- Vertex Pharmaceuticals Incorporated
- Enrollment
- 1164
- Primary Endpoint
- Part A Treatment Cohort: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of long-term treatment with lumacaftor in combination with ivacaftor in people 12 years and older with Cystic Fibrosis.
Detailed Description
This is a Phase 3, parallel group, multicenter, rollover study in participants with CF who are homozygous or heterozygous for the F508del CFTR mutation and who previously participated in Study 103 (Study VX12-809-103, NCT01807923), Study 104 (Study VX12-809-104, NCT01807949), or Cohort 4 of Study 102 (Study VX09-809-102, NCT01225211).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed informed consent form (ICF), and where appropriate, signed assent form.
- •Participants entering the Part A Treatment Cohort: Completed 24 weeks of study drug treatment in Study 103 or Study 104 and elect to enroll in Part A treatment cohort.
- •Participants entering the Part B Treatment Cohort: Completed 56 days of study drug treatment in Cohort 4 of Study 102 and elect to enroll in Part B treatment cohort.
- •Participants entering the Part A Observational Cohort: Completed 24 weeks of study drug treatment in Study 103 or Study 104, but do not elect to enroll in the Part A Treatment Cohort or do not qualify to enroll in Part A treatment cohort.
- •Willing to remain on a stable CF medication regimen through the end of study (Part A and Part B Treatment Cohorts only).
Exclusion Criteria
- •Any comorbidity or laboratory abnormality 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 participant (e.g., cirrhosis with portal hypertension).
- •Pregnant and nursing females. Females of childbearing potential must have a negative pregnancy test at the Day 1 Visit.
- •History of drug intolerance in the prior study that would pose an additional risk to the participant in the opinion of investigator or Vertex.
- •History of poor compliance with study drug and/or procedures in the previous study as deemed by the investigator.
- •Participation in an investigational drug trial (including studies investigating lumacaftor and/or ivacaftor, or studies requiring blood collections with or without administration of study drug)
Arms & Interventions
Arm 1 Part A: LUM 600 mg qd/ IVA 250 mg q12h
Participants who received lumacaftor (LUM, VX-809) 600 milligram (mg) plus ivacaftor (IVA, VX-770) 250 mg fixed-dose combination (FDC) tablet orally in the morning and IVA 250 mg film-coated tablet orally in the evening, in the previous study VX12-809-103 or VX12-809-104, and will receive the same treatment in this study VX12-809-105 up to Week 96.
Intervention: Lumacaftor Plus Ivacaftor Combination
Arm 1 Part A: LUM 600 mg qd/ IVA 250 mg q12h
Participants who received lumacaftor (LUM, VX-809) 600 milligram (mg) plus ivacaftor (IVA, VX-770) 250 mg fixed-dose combination (FDC) tablet orally in the morning and IVA 250 mg film-coated tablet orally in the evening, in the previous study VX12-809-103 or VX12-809-104, and will receive the same treatment in this study VX12-809-105 up to Week 96.
Intervention: Ivacaftor
Arm 4 Part A: Placebo - LUM 400 mg q12h/ IVA 250 mg q12h
Participants who received placebo matched to LUM and IVA tablet in the previous study VX12-809-103 or VX12-809-104, and will receive LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening in this study VX12-809-105 up to Week 96.
Intervention: Lumacaftor Plus Ivacaftor Combination
Arm 2 Part A: Placebo - LUM 600 mg qd/ IVA 250 mg q12h
Participants who received placebo matched to LUM and IVA tablet in the previous study VX12-809-103 or VX12-809-104, and will receive LUM 600 mg plus IVA 250 mg FDC tablet orally in the morning and IVA 250 mg film-coated tablet orally in the evening in this study VX12-809-105 up to Week 96.
Intervention: Lumacaftor Plus Ivacaftor Combination
Arm 2 Part A: Placebo - LUM 600 mg qd/ IVA 250 mg q12h
Participants who received placebo matched to LUM and IVA tablet in the previous study VX12-809-103 or VX12-809-104, and will receive LUM 600 mg plus IVA 250 mg FDC tablet orally in the morning and IVA 250 mg film-coated tablet orally in the evening in this study VX12-809-105 up to Week 96.
Intervention: Ivacaftor
Arm 3 Part A: LUM 400 mg q12h/ IVA 250 mg q12h
Participants who received LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening in the previous study VX12-809-103 or VX12-809-104, and will receive the same treatment in this study VX12-809-105 up to Week 96.
Intervention: Lumacaftor Plus Ivacaftor Combination
Arm 6 Part B: LUM 400 mg q12h/ IVA 250 mg q12h
Participants who received LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening in Cohort 4 of the previous study VX09-809-102, and will receive the same treatment in this study VX12-809-105 up to Week 96.
Intervention: Lumacaftor Plus Ivacaftor Combination
Arm 7 Part B: Placebo - LUM 400 mg q12h/ IVA 250 mg q12h
Participants who received placebo matched to LUM and IVA tablet in Cohort 4 of the previous study VX09-809-102, and will receive LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening in this study VX12-809-105 up to Week 96.
Intervention: Lumacaftor Plus Ivacaftor Combination
Outcomes
Primary Outcomes
Part A Treatment Cohort: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Day 1 up to Week 105 (Study 105)
AE: as any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, In-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Any AE that increased in severity or newly developed at or after initial dosing of study drug was considered treatment-emergent.
Part B Treatment Cohort: Number of Participants With Treatment-Emergent AEs and SAEs
Time Frame: Day 1 up to Week 105 (Study 105)
AE: as any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, In-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Any AE that increased in severity or newly developed at or after initial dosing of study drug was considered treatment-emergent.
Secondary Outcomes
- Part A Treatment Cohort: Absolute Change From Baseline in Body Mass Index (BMI) at Day 15, Week 8, 16, 24, 36, 48, 60 and 72(Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105))
- Part A Treatment Cohort: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) At Day 15, Week 8, 16, 24, 36, 48, 60 and 72(Baseline (Study 103/104/105); Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105))
- Part B Treatment Cohort: Absolute Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72(Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105))
- Part A Treatment Cohort: Relative Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72(Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105))
- Part B Treatment Cohort: Relative Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72(Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105))
- Part B Treatment Cohort: Absolute Change From Baseline in BMI at Day 15, Week 8, 16, 24, 36, 48, 60 and 72(Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105))
- Part A Treatment Cohort: Number of Pulmonary Exacerbations Events Per Patient-Year(Baseline (Study 103/104) up to Week 100 (Study 105) for Arm 1 and 3 (Cumulative study period); Baseline (Study 105) up to Week 100 (Study 105) for Arm 2 and 4 (current study period))
- Part A Treatment Cohort: Absolute Change From Baseline in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Domain Score at Day 15, Week 8, 16, 24, 48 and 72(Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 48, 72 (Study 105))
- Part B Treatment Cohort: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 15, Week 8, 16, 24, 48 and 72(Baseline (Study 102 Study), Day 15, Week 8, 16, 24, 48, 72 (Study 105))
- Part A Treatment Cohort: Absolute Change From Baseline in BMI Z-score at Day 15, Week 8, 16, 24, 36, 48, 60 and 72(Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105))
- Part A Treatment Cohort: Absolute Change From Baseline in Body Weight at Day 15, Week 8, 16, 24, 36, 48, 60 and 72(Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105))
- Part B Treatment Cohort: Absolute Change From Baseline in Body Weight at Day 15, Week 8, 16, 24, 36, 48, 60 and 72(Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105))
- Part A Treatment Cohort: Time-to-First Pulmonary Exacerbation(Baseline (Study 103/104) up to Week 100 (Study 105) for Arm 1 and 3 (Cumulative study period); Baseline (Study 105) up to Week 100 (Study 105) for Arm 2 and 4 (current study period))
- Part A Treatment Cohort: Percentage of Participants With at Least 1 Pulmonary Exacerbation(Baseline (Study 103/104) up to Week 100 (Study 105) for Arm 1 and 3 (Cumulative study period); Baseline (Study 105) up to Week 100 (Study 105) for Arm 2 and 4 (current study period))
- Part A Treatment Cohort: Percentage of Participants With Response Based on Relative Change in Percent Predicted FEV1 From Baseline(Baseline (Study 103/104/105); Day 15, Week 8, 16, 24, 36, 48, 60, 72, 84, 96 (Study 105))
- Part B Treatment Cohort: Percentage of Participants With Response Based on Relative Change in Percent Predicted FEV1 From Baseline(Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105))
- Part A Observation Cohort: Number of Participants With Serious Adverse Events (SAEs)(up to 2 years)