CClinicalTrials.gg
Sign In
CompletedNCT01931839Updated May 12, 2017Results posted

A Phase 3 Rollover Study of Lumacaftor in Combination With Ivacaftor in Subjects 12 Years and Older With Cystic Fibrosis

A Phase 3 interventional study of Lumacaftor Plus Ivacaftor Combination and Ivacaftor in Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation, sponsored by Vertex Pharmaceuticals Incorporated. Completed at 167 sites in 15 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2017-05-12.

Sponsored by Vertex Pharmaceuticals Incorporated · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
1,164
Allocation
Randomized
Ages
12 Years and older
Sex
All
01

Study 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.

Read the 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).

02

Conditions studied

  • Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation
03

In context

Cystic Fibrosis

1,581 studies on the registry are indexed under Cystic Fibrosis; 190 are open to participants now.

This study's enrollment of 1,164 is above the median of 36 across 1,034 interventional studies indexed under Cystic Fibrosis.

Browse Cystic Fibrosis studies →

Lead sponsor

Vertex Pharmaceuticals Incorporated is the lead sponsor of 243 studies on the registry; 19 are open to participants now.

Of its 102 completed or terminated interventional studies of FDA-regulated products, 49 (48%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
12 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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)
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
1,164 participants (actual)

Study arms

  • Experimental
    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.

    Drug: Lumacaftor Plus Ivacaftor Combination · Drug: Ivacaftor

  • Experimental
    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.

    Drug: Lumacaftor Plus Ivacaftor Combination · Drug: Ivacaftor

  • Experimental
    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.

    Drug: Lumacaftor Plus Ivacaftor Combination

  • Experimental
    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.

    Drug: Lumacaftor Plus Ivacaftor Combination

  • No intervention
    Arm 5 Part A: Observational Cohort

    Participants who received either LUM 600 mg plus IVA 250 mg FDC tablet orally in the morning and IVA 250 mg film-coated tablet orally in the evening OR LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening OR placebo matched to LUM and IVA in the morning and evening, in the previous study VX12-809-103 or VX12-809-104, and will be observed (will not receive study drug) in this study VX12-809-105 for up to 2 years.

  • Experimental
    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.

    Drug: Lumacaftor Plus Ivacaftor Combination

  • Experimental
    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.

    Drug: Lumacaftor Plus Ivacaftor Combination

Interventions

  • DrugLumacaftor Plus Ivacaftor Combination

    Fixed dose combination tablet, oral use

  • DrugIvacaftor

    Film-coated tablet, oral use

06

What researchers measure

Primary outcomes

  1. Part A Treatment Cohort: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    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.

    Time frame: Day 1 up to Week 105 (Study 105)

  2. Part B Treatment Cohort: Number of Participants With Treatment-Emergent AEs and SAEs

    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.

    Time frame: Day 1 up to Week 105 (Study 105)

Secondary outcomes

  1. 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

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, race, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Analysis was performed using baseline of the previous study VX12-809-103 (NCT01807923) and Study VX12-809-104 (NCT01807949) for Arm 1 and 3. Analysis was performed using baseline of the current study VX12-809-105 (NCT01931839) for Arm 2 and 4.

    Time frame: Baseline (Study 103/104/105); Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)

  2. Part B Treatment Cohort: Absolute Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, race, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Analysis was performed using baseline of Cohort 4 of previous study VX09-809-102 (NCT01225211) for Arm 6 and 7.

    Time frame: Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)

  3. Part A Treatment Cohort: Relative Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, race, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Analysis was performed using baseline of the previous study VX12-809-103 (NCT01807923) and Study VX12-809-104 (NCT01807949) for Arm 1 and 3. Analysis was performed using baseline of the current study VX12-809-105 (NCT01931839) for Arm 2 and 4.

    Time frame: Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)

  4. Part B Treatment Cohort: Relative Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, race, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Analysis was performed using baseline of Cohort 4 of previous study VX09-809-102 (NCT01225211) for Arm 6 and 7.

    Time frame: Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)

  5. 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

    BMI = (Weight in kilogram \[kg\]) divided by (Stature in meters \[m\]) \^2. Analysis was performed using baseline of the previous study VX12-809-103 (NCT01807923) and Study VX12-809-104 (NCT01807949) for Arm 1 and 3. Analysis was performed using baseline of the current study VX12-809-105 (NCT01931839) for Arm 2 and 4.

    Time frame: Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)

  6. Part B Treatment Cohort: Absolute Change From Baseline in BMI at Day 15, Week 8, 16, 24, 36, 48, 60 and 72

    BMI = (Weight \[in kg\]) divided by (Stature \[in meters\]) \^2. Analysis was performed using baseline of Cohort 4 of previous study VX09-809-102 (NCT01225211) for Arm 6 and 7.

    Time frame: Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)

  7. Part A Treatment Cohort: Number of Pulmonary Exacerbations Events Per Patient-Year

    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. The number of events per patient year were reported, where patient years = total number of days on study/336. Analysis includes all events in the Cumulative Study Period for Arm 1 and 3, and all events in the Current Study period (Study 105) for Arm 2 and 4. As per planned analysis, endpoint evaluation included subjects from the parent study VX12-809-103 and VX12-809-104 as well for cumulative study period.

    Time frame: 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)

  8. 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

    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 (for example, coughing, congestion, wheezing), the scaled score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Analysis was performed using baseline of the previous study VX12-809-103 (NCT01807923) and Study VX12-809-104 (NCT01807949) for Arm 1 and 3. Analysis was performed using baseline of the current study VX12-809-105 (NCT01931839) for Arm 2 and 4.

    Time frame: Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 48, 72 (Study 105)

  9. Part B Treatment Cohort: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 15, Week 8, 16, 24, 48 and 72

    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 (for example, coughing, congestion, wheezing), the scaled score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Analysis was performed using baseline of Cohort 4 of previous study VX09-809-102 (NCT01225211) for Arm 6 and 7.

    Time frame: Baseline (Study 102 Study), Day 15, Week 8, 16, 24, 48, 72 (Study 105)

  10. Part A Treatment Cohort: Absolute Change From Baseline in BMI Z-score at Day 15, Week 8, 16, 24, 36, 48, 60 and 72

    z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard and how unusual the measurement is with range from -infinity to +infinity; 0: same mean, \>0: a greater mean, and \<0: a lesser mean than the standard. BMI-for-age z-score was calculated by using centers for disease control and prevention (CDC) growth charts for the pediatric population. Analysis was performed using baseline of the previous study VX12-809-103 (NCT01807923) and Study VX12-809-104 (NCT01807949) for Arm 1 and 3. Analysis was performed using baseline of the current study VX12-809-105 (NCT01931839) for Arm 2 and 4.

    Time frame: Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)

  11. Part A Treatment Cohort: Absolute Change From Baseline in Body Weight at Day 15, Week 8, 16, 24, 36, 48, 60 and 72

    Analysis was performed using baseline of the previous study VX12-809-103 (NCT01807923) and Study VX12-809-104 (NCT01807949) for Arm 1 and 3. Analysis was performed using baseline of the current study VX12-809-105 (NCT01931839) for Arm 2 and 4.

    Time frame: Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)

  12. Part B Treatment Cohort: Absolute Change From Baseline in Body Weight at Day 15, Week 8, 16, 24, 36, 48, 60 and 72

    Analysis was performed using baseline of Cohort 4 of previous study VX09-809-102 (NCT01225211) for Arm 6 and 7.

    Time frame: Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)

  13. Part A Treatment Cohort: Time-to-First Pulmonary Exacerbation

    Time-to-first pulmonary exacerbation was analyzed using the Kaplan-Meier estimates. 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. Analysis was performed for the Cumulative Study Period for Arm 1 and 3, and for the current study period (Study 105) for Arm 2 and 4. As per planned analysis, endpoint evaluation included subjects from the parent study VX12-809-103 and VX12-809-104 as well for cumulative study period.

    Time frame: 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)

  14. Part A Treatment Cohort: Percentage of Participants With at Least 1 Pulmonary Exacerbation

    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. Analysis was performed for the Cumulative Study Period for Arm 1 and 3, and for the current study period (Study 105) for Arm 2 and 4. As per planned analysis, endpoint evaluation included subjects from the parent study VX12-809-103 and VX12-809-104 as well for cumulative study period.

    Time frame: 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)

  15. Part A Treatment Cohort: Percentage of Participants With Response Based on Relative Change in Percent Predicted FEV1 From Baseline

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, race, and height). Percentage of participants with at least 5% and 10% relative change in percent predicted FEV1 from baseline were reported. Analysis was performed using baseline of the previous study VX12-809-103 (NCT01807923) and Study VX12-809-104 (NCT01807949) for Arm 1 and 3. Analysis was performed using baseline of the current study VX12-809-105 (NCT01931839) for Arm 2 and 4. As per planned analysis, endpoint evaluation included subjects from the parent study VX12-809-103 and VX12-809-104 as well for cumulative study period.

    Time frame: Baseline (Study 103/104/105); Day 15, Week 8, 16, 24, 36, 48, 60, 72, 84, 96 (Study 105)

  16. Part B Treatment Cohort: Percentage of Participants With Response Based on Relative Change in Percent Predicted FEV1 From Baseline

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, race, and height). Percentage of participants with at least 5% relative change in percent predicted FEV1 from Baseline were reported. Analysis was performed using baseline of Cohort 4 of previous study VX09-809-102 (NCT01225211) for Arm 6 and 7. As per planned analysis, endpoint evaluation included subjects from the parent study VX09-809-102 as well.

    Time frame: Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)

  17. Part A Observation Cohort: Number of Participants With Serious Adverse Events (SAEs)

    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 the 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.

    Time frame: up to 2 years

07

Results

Posted May 12, 2017
Limitations and caveats
Analysis using baseline values of the current study 105 (NCT01931839) was not performed for Part B Treatment Cohort.

Participant flow

Study conducted in 2 parts: A \& B. Part A consisted of Treatment Cohorts \& Observational Cohort, which enrolled participants from Study VX12-809-103 (Study 103, NCT01807923) \& Study VX12-809-104 (Study 104, NCT01807949). Part B consisted of Treatment Cohorts which enrolled participants from Cohort 4 of Study VX09-809-102 (Study 102, NCT01225211).

Participant flow — Overall Study
MilestoneArm 1 Part A: LUM 600 mg qd/ IVA 250 mg q12hArm 2 Part A: Placebo - LUM 600 mg qd/ IVA 250 mg q12hArm 3 Part A: LUM 400 mg q12h/ IVA 250 mg q12hArm 4 Part A: Placebo - LUM 400 mg q12h/ IVA 250 mg q12hArm 5 Part A: Observational CohortArm 6 Part B: LUM 400 mg q12h/ IVA 250 mg q12hArm 7 Part B: Placebo - LUM 400 mg q12h/ IVA 250 mg q12h
Started335178340176195560
Full analysis set (as randomized)334179340176195560
Safety analysis set (as dosed)335178340176195560
Completed294152301162185056
Not completed41263914154
Withdrew: Death0120000
Withdrew: Physician decision1010001
Withdrew: Withdrawal of consent0000100
Withdrew: Adverse event9413001
Withdrew: Withdrawal of consent (not due to ae)118133022
Withdrew: Other non-compliance159123030
Withdrew: Lost to follow-up1245000
Withdrew: Other4260000

Outcome measures

PrimaryPart A Treatment Cohort: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

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.

Time frame:
Day 1 up to Week 105 (Study 105)
Reported as:
Number · participants
Part A Treatment Cohort: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
participantsArm 1: Part A - LUM 600 mg qd/ IVA 250 mg q12hArm 2: Part A - Placebo- LUM 600 mg qd/ IVA 250 mg q12hArm 3: Part A - LUM 400 mg q12h/ IVA 250 mg q12hArm 4: Part A - Placebo- LUM 400 mg q12h/ IVA 250 mg q12h
Participants with any AEs331177333176
Participants with SAEs1567714389
PrimaryPart B Treatment Cohort: Number of Participants With Treatment-Emergent AEs and SAEs

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.

Time frame:
Day 1 up to Week 105 (Study 105)
Reported as:
Number · participants
Part B Treatment Cohort: Number of Participants With Treatment-Emergent AEs and SAEs
participantsArm 6: Part B LUM 400 mg q12h/ IVA 250 mg q12hArm 7: Part B Placebo- LUM 400 mg q12h/ IVA 250 mg q12h
Participants with AEs5257
Participants with SAEs1821
SecondaryPart 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

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, race, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Analysis was performed using baseline of the previous study VX12-809-103 (NCT01807923) and Study VX12-809-104 (NCT01807949) for Arm 1 and 3. Analysis was performed using baseline of the current study VX12-809-105 (NCT01931839) for Arm 2 and 4.

Time frame:
Baseline (Study 103/104/105); Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)
Reported as:
Least squares mean · percent predicted of FEV1
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
percent predicted of FEV1Arm 1: Part A - LUM 600 mg qd/ IVA 250 mg q12hArm 2: Part A - Placebo- LUM 600 mg qd/ IVA 250 mg q12hArm 3: Part A - LUM 400 mg q12h/ IVA 250 mg q12hArm 4: Part A - Placebo- LUM 400 mg q12h/ IVA 250 mg q12h
Absolute Change at Day 153 ± 0.52.8 ± 0.62.8 ± 0.53 ± 0.6
Absolute Change at Week 83.1 ± 0.52.8 ± 0.63.4 ± 0.54.2 ± 0.6
Absolute Change at Week 162.6 ± 0.52.7 ± 0.62.5 ± 0.53.6 ± 0.7
Absolute Change at Week 242.9 ± 0.52.4 ± 0.62.7 ± 0.53.4 ± 0.7
Absolute Change at Week 362.7 ± 0.52.2 ± 0.71.9 ± 0.53.1 ± 0.7
Absolute Change at Week 481.5 ± 0.51.8 ± 0.71.4 ± 0.52.1 ± 0.7
Absolute Change at Week 601.7 ± 0.52.1 ± 0.71.6 ± 0.51.4 ± 0.7
Absolute Change at Week 721.2 ± 0.51.9 ± 0.70.5 ± 0.51.5 ± 0.7
SecondaryPart B Treatment Cohort: Absolute Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, race, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Analysis was performed using baseline of Cohort 4 of previous study VX09-809-102 (NCT01225211) for Arm 6 and 7.

Time frame:
Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)
Reported as:
Mean · percent predicted of FEV1
Part B Treatment Cohort: Absolute Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72
percent predicted of FEV1Arm 6: Part B LUM 400 mg q12h/ IVA 250 mg q12hArm 7: Part B Placebo- LUM 400 mg q12h/ IVA 250 mg q12h
Absolute Change at Day 15-2 ± 8-3.4 ± 6.6
Absolute Change at Week 8-3.9 ± 7.4-1.8 ± 6.4
Absolute Change at Week 16-3.1 ± 9-2.8 ± 6.8
Absolute Change at Week 24-2.9 ± 7.7-2.5 ± 7.3
Absolute Change at Week 36-3.2 ± 7.9-2.3 ± 7.9
Absolute Change at Week 48-5.4 ± 11.2-2 ± 6
Absolute Change at Week 60-1.8 ± 10.1-1.9 ± 8.2
Absolute Change at Week 72-2.8 ± 9.2-7.8 ± 8.3
SecondaryPart A Treatment Cohort: Relative Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, race, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Analysis was performed using baseline of the previous study VX12-809-103 (NCT01807923) and Study VX12-809-104 (NCT01807949) for Arm 1 and 3. Analysis was performed using baseline of the current study VX12-809-105 (NCT01931839) for Arm 2 and 4.

Time frame:
Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)
Reported as:
Least squares mean · percent change
Part A Treatment Cohort: Relative Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72
percent changeArm 1: Part A - LUM 600 mg qd/ IVA 250 mg q12hArm 2: Part A - Placebo- LUM 600 mg qd/ IVA 250 mg q12hArm 3: Part A - LUM 400 mg q12h/ IVA 250 mg q12hArm 4: Part A - Placebo- LUM 400 mg q12h/ IVA 250 mg q12h
Relative Change at Day 155.3 ± 0.95.1 ± 1.25.3 ± 0.94.8 ± 1.2
Relative Change at Week 85.6 ± 0.95.6 ± 1.26.2 ± 0.97.1 ± 1.2
Relative Change at Week 164.9 ± 0.95.4 ± 1.24.8 ± 0.96.5 ± 1.2
Relative Change at Week 245.1 ± 0.94.9 ± 1.25 ± 0.96.1 ± 1.2
Relative Change at Week 364.7 ± 0.94 ± 1.23.6 ± 0.95.5 ± 1.2
Relative Change at Week 482.7 ± 0.93.6 ± 1.22.9 ± 0.93.6 ± 1.2
Relative Change at Week 602.9 ± 0.94.1 ± 1.22.7 ± 0.93.1 ± 1.2
Relative Change at Week 722.4 ± 0.93.8 ± 1.21.4 ± 0.92.6 ± 1.2
SecondaryPart B Treatment Cohort: Relative Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, race, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Analysis was performed using baseline of Cohort 4 of previous study VX09-809-102 (NCT01225211) for Arm 6 and 7.

Time frame:
Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)
Reported as:
Mean · percent change
Part B Treatment Cohort: Relative Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72
percent changeArm 6: Part B LUM 400 mg q12h/ IVA 250 mg q12hArm 7: Part B Placebo- LUM 400 mg q12h/ IVA 250 mg q12h
Relative Change at Day 15-2.2 ± 13.6-5.8 ± 11.4
Relative Change at Week 8-5.2 ± 12.8-3.1 ± 11.4
Relative Change at Week 16-4.2 ± 15.8-4.9 ± 11.8
Relative Change at Week 24-3.4 ± 13.2-4.2 ± 12.6
Relative Change at Week 36-4.1 ± 12.5-3.5 ± 14.2
Relative Change at Week 48-6.9 ± 15.9-2.8 ± 10.6
Relative Change at Week 60-0.7 ± 16.6-2.6 ± 13.9
Relative Change at Week 72-3.3 ± 13.3-11.8 ± 10.7
SecondaryPart A Treatment Cohort: Absolute Change From Baseline in Body Mass Index (BMI) at Day 15, Week 8, 16, 24, 36, 48, 60 and 72

BMI = (Weight in kilogram \[kg\]) divided by (Stature in meters \[m\]) \^2. Analysis was performed using baseline of the previous study VX12-809-103 (NCT01807923) and Study VX12-809-104 (NCT01807949) for Arm 1 and 3. Analysis was performed using baseline of the current study VX12-809-105 (NCT01931839) for Arm 2 and 4.

Time frame:
Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)
Reported as:
Least squares mean · Kilogram per square meter (kg/m^2)
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
Kilogram per square meter (kg/m^2)Arm 1: Part A - LUM 600 mg qd/ IVA 250 mg q12hArm 2: Part A - Placebo- LUM 600 mg qd/ IVA 250 mg q12hArm 3: Part A - LUM 400 mg q12h/ IVA 250 mg q12hArm 4: Part A - Placebo- LUM 400 mg q12h/ IVA 250 mg q12h
Absolute Change at Day 150.56 ± 0.060.06 ± 0.080.5 ± 0.060.1 ± 0.08
Absolute Change at Week 80.58 ± 0.060.14 ± 0.080.55 ± 0.060.27 ± 0.08
Absolute Change at Week 160.58 ± 0.060.19 ± 0.080.53 ± 0.060.35 ± 0.08
Absolute Change at Week 240.61 ± 0.060.22 ± 0.080.62 ± 0.060.41 ± 0.08
Absolute Change at Week 360.66 ± 0.060.33 ± 0.080.72 ± 0.060.59 ± 0.08
Absolute Change at Week 480.63 ± 0.060.42 ± 0.080.71 ± 0.060.62 ± 0.09
Absolute Change at Week 600.71 ± 0.060.54 ± 0.080.8 ± 0.060.62 ± 0.09
Absolute Change at Week 720.72 ± 0.060.52 ± 0.080.69 ± 0.060.62 ± 0.09
SecondaryPart B Treatment Cohort: Absolute Change From Baseline in BMI at Day 15, Week 8, 16, 24, 36, 48, 60 and 72

BMI = (Weight \[in kg\]) divided by (Stature \[in meters\]) \^2. Analysis was performed using baseline of Cohort 4 of previous study VX09-809-102 (NCT01225211) for Arm 6 and 7.

Time frame:
Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)
Reported as:
Mean · kg/m^2
Part B Treatment Cohort: Absolute Change From Baseline in BMI at Day 15, Week 8, 16, 24, 36, 48, 60 and 72
kg/m^2Arm 6: Part B LUM 400 mg q12h/ IVA 250 mg q12hArm 7: Part B Placebo- LUM 400 mg q12h/ IVA 250 mg q12h
Absolute Change at Day 15-0.05 ± 0.52-0.03 ± 0.69
Absolute Change at Week 8-0.01 ± 0.820.14 ± 0.84
Absolute Change at Week 160.08 ± 1.020.2 ± 1.09
Absolute Change at Week 240.04 ± 0.920.14 ± 1.08
Absolute Change at Week 360.07 ± 0.540.85 ± 1.23
Absolute Change at Week 480.05 ± 0.640.81 ± 1.55
Absolute Change at Week 600.08 ± 0.70.58 ± 1.23
Absolute Change at Week 720.08 ± 0.710.41 ± 1.28
SecondaryPart A Treatment Cohort: Number of Pulmonary Exacerbations Events Per Patient-Year

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. The number of events per patient year were reported, where patient years = total number of days on study/336. Analysis includes all events in the Cumulative Study Period for Arm 1 and 3, and all events in the Current Study period (Study 105) for Arm 2 and 4. As per planned analysis, endpoint evaluation included subjects from the parent study VX12-809-103 and VX12-809-104 as well for cumulative study period.

Time frame:
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)
Reported as:
Number · events per patient year
Part A Treatment Cohort: Number of Pulmonary Exacerbations Events Per Patient-Year
events per patient yearArm 1: Part A - LUM 600 mg qd/ IVA 250 mg q12hArm 2: Part A - Placebo- LUM 600 mg qd/ IVA 250 mg q12hArm 3: Part A - LUM 400 mg q12h/ IVA 250 mg q12hArm 4: Part A - Placebo- LUM 400 mg q12h/ IVA 250 mg q12h
Part A Treatment Cohort: Number of Pulmonary Exacerbations Events Per Patient-Year0.38 (0.32 to 0.46)0.42 (0.33 to 0.54)0.32 (0.26 to 0.38)0.37 (0.29 to 0.49)
SecondaryPart 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

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 (for example, coughing, congestion, wheezing), the scaled score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Analysis was performed using baseline of the previous study VX12-809-103 (NCT01807923) and Study VX12-809-104 (NCT01807949) for Arm 1 and 3. Analysis was performed using baseline of the current study VX12-809-105 (NCT01931839) for Arm 2 and 4.

Time frame:
Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 48, 72 (Study 105)
Reported as:
Least squares mean · units on a scale
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
units on a scaleArm 1: Part A - LUM 600 mg qd/ IVA 250 mg q12hArm 2: Part A - Placebo- LUM 600 mg qd/ IVA 250 mg q12hArm 3: Part A - LUM 400 mg q12h/ IVA 250 mg q12hArm 4: Part A - Placebo- LUM 400 mg q12h/ IVA 250 mg q12h
Absolute Change at Day 155.9 ± 0.92.3 ± 1.26.2 ± 0.93.5 ± 1.2
Absolute Change at Week 85 ± 0.94.1 ± 1.25.1 ± 0.96.8 ± 1.2
Absolute Change at Week 164.1 ± 0.92.8 ± 1.26.4 ± 0.97 ± 1.2
Absolute Change at Week 246 ± 0.93.8 ± 1.26.1 ± 0.94.7 ± 1.3
Absolute Change at Week 482 ± 0.93.1 ± 1.33.7 ± 0.91.5 ± 1.3
Absolute Change at Week 723.2 ± 0.93.3 ± 1.35.7 ± 0.93.3 ± 1.3
SecondaryPart B Treatment Cohort: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 15, Week 8, 16, 24, 48 and 72

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 (for example, coughing, congestion, wheezing), the scaled score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Analysis was performed using baseline of Cohort 4 of previous study VX09-809-102 (NCT01225211) for Arm 6 and 7.

Time frame:
Baseline (Study 102 Study), Day 15, Week 8, 16, 24, 48, 72 (Study 105)
Reported as:
Mean · units on a scale
Part B Treatment Cohort: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 15, Week 8, 16, 24, 48 and 72
units on a scaleArm 6: Part B LUM 400 mg q12h/ IVA 250 mg q12hArm 7: Part B Placebo- LUM 400 mg q12h/ IVA 250 mg q12h
Absolute Change at Day 153.9 ± 18-4.1 ± 18.1
Absolute Change at Week 84.8 ± 18.61 ± 18.2
Absolute Change at Week 166.2 ± 17.2-0.2 ± 17
Absolute Change at Week 246.8 ± 19.1-1.2 ± 17.9
Absolute Change at Week 482 ± 144.9 ± 15.6
Absolute Change at Week 728.5 ± 21.82.2 ± 18.8
SecondaryPart A Treatment Cohort: Absolute Change From Baseline in BMI Z-score at Day 15, Week 8, 16, 24, 36, 48, 60 and 72

z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard and how unusual the measurement is with range from -infinity to +infinity; 0: same mean, \>0: a greater mean, and \<0: a lesser mean than the standard. BMI-for-age z-score was calculated by using centers for disease control and prevention (CDC) growth charts for the pediatric population. Analysis was performed using baseline of the previous study VX12-809-103 (NCT01807923) and Study VX12-809-104 (NCT01807949) for Arm 1 and 3. Analysis was performed using baseline of the current study VX12-809-105 (NCT01931839) for Arm 2 and 4.

Time frame:
Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)
Reported as:
Least squares mean · z-score
Part A Treatment Cohort: Absolute Change From Baseline in BMI Z-score at Day 15, Week 8, 16, 24, 36, 48, 60 and 72
z-scoreArm 1: Part A - LUM 600 mg qd/ IVA 250 mg q12hArm 2: Part A - Placebo- LUM 600 mg qd/ IVA 250 mg q12hArm 3: Part A - LUM 400 mg q12h/ IVA 250 mg q12hArm 4: Part A - Placebo- LUM 400 mg q12h/ IVA 250 mg q12h
Absolute Change at Day 150.16 ± 0.04-0.01 ± 0.060.14 ± 0.04-0.02 ± 0.05
Absolute Change at Week 80.15 ± 0.040.04 ± 0.060.16 ± 0.040.08 ± 0.05
Absolute Change at Week 160.12 ± 0.040.08 ± 0.060.15 ± 0.040.07 ± 0.05
Absolute Change at Week 240.14 ± 0.040.08 ± 0.060.17 ± 0.040.1 ± 0.05
Absolute Change at Week 360.14 ± 0.040.13 ± 0.060.16 ± 0.040.14 ± 0.05
Absolute Change at Week 480.09 ± 0.040.13 ± 0.060.11 ± 0.040.12 ± 0.06
Absolute Change at Week 600.11 ± 0.040.16 ± 0.060.14 ± 0.040.13 ± 0.06
Absolute Change at Week 720.06 ± 0.040.12 ± 0.060.04 ± 0.040.08 ± 0.06
SecondaryPart A Treatment Cohort: Absolute Change From Baseline in Body Weight at Day 15, Week 8, 16, 24, 36, 48, 60 and 72

Analysis was performed using baseline of the previous study VX12-809-103 (NCT01807923) and Study VX12-809-104 (NCT01807949) for Arm 1 and 3. Analysis was performed using baseline of the current study VX12-809-105 (NCT01931839) for Arm 2 and 4.

Time frame:
Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)
Reported as:
Mean · kilograms (kg)
Part A Treatment Cohort: Absolute Change From Baseline in Body Weight at Day 15, Week 8, 16, 24, 36, 48, 60 and 72
kilograms (kg)Arm 1: Part A - LUM 600 mg qd/ IVA 250 mg q12hArm 2: Part A - Placebo- LUM 600 mg qd/ IVA 250 mg q12hArm 3: Part A - LUM 400 mg q12h/ IVA 250 mg q12hArm 4: Part A - Placebo- LUM 400 mg q12h/ IVA 250 mg q12h
Absolute Change at Day 151.7 ± 2.6-0.1 ± 1.81.3 ± 2.90.1 ± 1.2
Absolute Change at Week 81.8 ± 2.90.2 ± 2.11.5 ± 3.10.6 ± 1.9
Absolute Change at Week 161.9 ± 3.20.4 ± 2.61.6 ± 3.31 ± 2.5
Absolute Change at Week 242.2 ± 3.50.6 ± 2.62 ± 3.61.2 ± 2.8
Absolute Change at Week 362.3 ± 3.81 ± 3.42.4 ± 3.81.9 ± 3.4
Absolute Change at Week 482.4 ± 4.21.3 ± 3.72.5 ± 4.32.1 ± 3.7
Absolute Change at Week 602.7 ± 4.61.7 ± 4.22.9 ± 4.62.2 ± 4.4
Absolute Change at Week 722.9 ± 4.91.7 ± 4.82.7 ± 4.92.3 ± 4.7
SecondaryPart B Treatment Cohort: Absolute Change From Baseline in Body Weight at Day 15, Week 8, 16, 24, 36, 48, 60 and 72

Analysis was performed using baseline of Cohort 4 of previous study VX09-809-102 (NCT01225211) for Arm 6 and 7.

Time frame:
Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)
Reported as:
Mean · kg
Part B Treatment Cohort: Absolute Change From Baseline in Body Weight at Day 15, Week 8, 16, 24, 36, 48, 60 and 72
kgArm 6: Part B LUM 400 mg q12h/ IVA 250 mg q12hArm 7: Part B Placebo- LUM 400 mg q12h/ IVA 250 mg q12h
Absolute Change at Day 15-0.1 ± 1.5-0.1 ± 1.8
Absolute Change at Week 80 ± 2.30.4 ± 2.3
Absolute Change at Week 160.3 ± 2.80.6 ± 2.9
Absolute Change at Week 240.2 ± 2.60.4 ± 3
Absolute Change at Week 360.3 ± 1.72.3 ± 3.3
Absolute Change at Week 480.2 ± 22.2 ± 4.3
Absolute Change at Week 600.3 ± 2.31.5 ± 3.3
Absolute Change at Week 720.2 ± 2.31.1 ± 3.4
SecondaryPart A Treatment Cohort: Time-to-First Pulmonary Exacerbation

Time-to-first pulmonary exacerbation was analyzed using the Kaplan-Meier estimates. 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. Analysis was performed for the Cumulative Study Period for Arm 1 and 3, and for the current study period (Study 105) for Arm 2 and 4. As per planned analysis, endpoint evaluation included subjects from the parent study VX12-809-103 and VX12-809-104 as well for cumulative study period.

Time frame:
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)
Reported as:
Median · days
Part A Treatment Cohort: Time-to-First Pulmonary Exacerbation
daysArm 1: Part A - LUM 600 mg qd/ IVA 250 mg q12hArm 2: Part A - Placebo- LUM 600 mg qd/ IVA 250 mg q12hArm 3: Part A - LUM 400 mg q12h/ IVA 250 mg q12hArm 4: Part A - Placebo- LUM 400 mg q12h/ IVA 250 mg q12h
Part A Treatment Cohort: Time-to-First Pulmonary Exacerbation364 (99 to NA)505 (111 to NA)481 (132 to NA)466 (153 to NA)
SecondaryPart A Treatment Cohort: Percentage of Participants With at Least 1 Pulmonary Exacerbation

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. Analysis was performed for the Cumulative Study Period for Arm 1 and 3, and for the current study period (Study 105) for Arm 2 and 4. As per planned analysis, endpoint evaluation included subjects from the parent study VX12-809-103 and VX12-809-104 as well for cumulative study period.

Time frame:
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)
Reported as:
Number · percentage of participants
Part A Treatment Cohort: Percentage of Participants With at Least 1 Pulmonary Exacerbation
percentage of participantsArm 1: Part A - LUM 600 mg qd/ IVA 250 mg q12hArm 2: Part A - Placebo- LUM 600 mg qd/ IVA 250 mg q12hArm 3: Part A - LUM 400 mg q12h/ IVA 250 mg q12hArm 4: Part A - Placebo- LUM 400 mg q12h/ IVA 250 mg q12h
Part A Treatment Cohort: Percentage of Participants With at Least 1 Pulmonary Exacerbation64.7 (59.8 to 69.6)53.6 (46.3 to 60.9)59.9 (54.9 to 64.9)55.7 (48.3 to 63)
SecondaryPart A Treatment Cohort: Percentage of Participants With Response Based on Relative Change in Percent Predicted FEV1 From Baseline

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, race, and height). Percentage of participants with at least 5% and 10% relative change in percent predicted FEV1 from baseline were reported. Analysis was performed using baseline of the previous study VX12-809-103 (NCT01807923) and Study VX12-809-104 (NCT01807949) for Arm 1 and 3. Analysis was performed using baseline of the current study VX12-809-105 (NCT01931839) for Arm 2 and 4. As per planned analysis, endpoint evaluation included subjects from the parent study VX12-809-103 and VX12-809-104 as well for cumulative study period.

Time frame:
Baseline (Study 103/104/105); Day 15, Week 8, 16, 24, 36, 48, 60, 72, 84, 96 (Study 105)
Reported as:
Number · percentage of participants
Part A Treatment Cohort: Percentage of Participants With Response Based on Relative Change in Percent Predicted FEV1 From Baseline
percentage of participantsArm 1: Part A - LUM 600 mg qd/ IVA 250 mg q12hArm 2: Part A - Placebo- LUM 600 mg qd/ IVA 250 mg q12hArm 3: Part A - LUM 400 mg q12h/ IVA 250 mg q12hArm 4: Part A - Placebo- LUM 400 mg q12h/ IVA 250 mg q12h
Day 15: >=5% Change39.4 (34.4 to 44.4)42.5 (35.2 to 49.7)40.9 (35.9 to 45.9)42.6 (35.3 to 49.9)
Day 15: >=10% Change25 (20.6 to 29.4)26.8 (20.3 to 33.3)24.7 (20.3 to 29.1)26.7 (20.2 to 33.2)
Week 8: >=5% Change39.7 (34.7 to 44.7)38 (30.9 to 45.1)39.3 (34.3 to 44.3)48.9 (41.5 to 56.2)
Week 8: >=10% Change26.9 (22.4 to 31.4)23.5 (17.3 to 29.7)26.6 (22.1 to 31.1)35.8 (28.7 to 42.9)
Week 16: >=5% Change37.2 (32.3 to 42.2)36.9 (29.8 to 43.9)36.9 (31.9 to 41.8)46.6 (39.2 to 54)
Week 16: >=10% Change25.5 (21.1 to 30)25.1 (18.8 to 31.5)26.3 (21.8 to 30.8)28.4 (21.7 to 35.1)
Week 24: >=5% Change35.6 (30.7 to 40.5)38 (30.9 to 45.1)33.6 (28.8 to 38.4)42.6 (35.3 to 49.9)
Week 24: >=10% Change24.5 (20.1 to 28.8)21.8 (15.7 to 27.8)22.5 (18.2 to 26.8)32.4 (25.5 to 39.3)
Week 36: >=5% Change35.3 (30.4 to 40.2)32.4 (25.5 to 39.3)31.7 (27 to 36.5)38.6 (31.4 to 45.8)
Week 36: >=10% Change23.4 (19 to 27.7)22.9 (16.7 to 29.1)22.2 (18 to 26.5)27.3 (20.7 to 33.9)
Week 48: >=5% Change30.2 (25.5 to 34.9)32.4 (25.5 to 39.3)30.9 (26.2 to 35.6)36.4 (29.3 to 43.5)
Week 48: >=10% Change21.7 (17.5 to 26)21.8 (15.7 to 27.8)21.4 (17.2 to 25.6)19.9 (14 to 25.8)
Week 60: >=5% Change30.4 (25.7 to 35.1)32.4 (25.5 to 39.3)29.3 (24.6 to 33.9)38.6 (31.4 to 45.8)
Week 60: >=10% Change20.4 (16.3 to 24.5)25.1 (18.8 to 31.5)19.2 (15.2 to 23.3)24.4 (18.1 to 30.8)
Week 72: >=5% Change29.3 (24.7 to 34)34.6 (27.7 to 41.6)25.5 (21 to 29.9)33 (26 to 39.9)
Week 72: >=10% Change18.2 (14.3 to 22.1)22.3 (16.2 to 28.4)18.2 (14.2 to 22.1)23.3 (17.1 to 29.5)
Week 84: >=5% Change23.1 (18.8 to 27.4)28.5 (21.9 to 35.1)23.3 (19 to 27.6)26.1 (19.6 to 32.6)
Week 84: >=10% Change14.9 (11.3 to 18.6)21.2 (15.2 to 27.2)15.7 (12 to 19.4)19.9 (14 to 25.8)
Week 96: >=5% Change15.5 (11.8 to 19.2)14.5 (9.4 to 19.7)13.8 (10.3 to 17.3)15.3 (10 to 20.7)
Week 96: >=10% Change8.7 (5.8 to 11.6)10.1 (5.7 to 14.5)10.3 (7.2 to 13.4)9.1 (4.8 to 13.3)
SecondaryPart B Treatment Cohort: Percentage of Participants With Response Based on Relative Change in Percent Predicted FEV1 From Baseline

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, race, and height). Percentage of participants with at least 5% relative change in percent predicted FEV1 from Baseline were reported. Analysis was performed using baseline of Cohort 4 of previous study VX09-809-102 (NCT01225211) for Arm 6 and 7. As per planned analysis, endpoint evaluation included subjects from the parent study VX09-809-102 as well.

Time frame:
Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)
Reported as:
Number · percentage of participants
Part B Treatment Cohort: Percentage of Participants With Response Based on Relative Change in Percent Predicted FEV1 From Baseline
percentage of participantsArm 6: Part B LUM 400 mg q12h/ IVA 250 mg q12hArm 7: Part B Placebo- LUM 400 mg q12h/ IVA 250 mg q12h
Day 15: >=5% Change21 (10.8 to 31.1)12.7 (4.5 to 20.9)
Week 8: >=5% Change11.3 (3.4 to 19.2)19 (9.4 to 28.7)
Week 16: >=5% Change19.4 (9.5 to 29.2)15.9 (6.8 to 24.9)
Week 24: >=5% Change12.9 (4.6 to 21.2)12.7 (4.5 to 20.9)
Week 36: >=5% Change6.5 (0.3 to 12.6)6.3 (0.3 to 12.4)
Week 48: >=5% Change6.5 (0.3 to 12.6)4.8 (0 to 10)
Week 60: >=5% Change6.5 (0.3 to 12.6)6.3 (0.3 to 12.4)
Week 72: >=5% Change3.2 (0 to 7.6)0 (0 to 0)
Week 84: >=5% Change1.6 (0 to 4.7)1.6 (0 to 4.7)
Week 96: >=5% Change0 (0 to 0)0 (0 to 0)
SecondaryPart A Observation Cohort: Number of Participants With Serious Adverse Events (SAEs)

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 the 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.

Time frame:
up to 2 years
Reported as:
Number · participants
Part A Observation Cohort: Number of Participants With Serious Adverse Events (SAEs)
participantsArm 5: Part A Observational Cohort
Part A Observation Cohort: Number of Participants With Serious Adverse Events (SAEs)7

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arm 1 Part A: LUM 600 mg qd/ IVA 250 mg q12h—156/335 (46.6%)328/335 (97.9%)
Arm 2 Part A: Placebo - LUM 600 mg qd/ IVA 250 mg q12h—77/178 (43.3%)177/178 (99.4%)
Arm 3 Part A: LUM 400 mg q12h/ IVA 250 mg q12h—143/340 (42.1%)332/340 (97.6%)
Arm 4 Part A: Placebo - LUM 400 mg q12h/ IVA 250 mg q12h—89/176 (50.6%)173/176 (98.3%)
Arm 5 Part A: Observational Cohort—7/19 (36.8%)—
Arm 6 Part B: LUM 400 mg q12h/ IVA 250 mg q12h—18/55 (32.7%)52/55 (94.5%)
Arm 7 Part B: Placebo - LUM 400 mg q12h/ IVA 250 mg q12h—21/60 (35%)57/60 (95%)
Most frequent serious events
Showing 10 of 145
Most frequent serious events
EventArm 1 Part A: LUM 600 mg qd/ IVA 250 mg q12hArm 2 Part A: Placebo - LUM 600 mg qd/ IVA 250 mg q12hArm 3 Part A: LUM 400 mg q12h/ IVA 250 mg q12hArm 4 Part A: Placebo - LUM 400 mg q12h/ IVA 250 mg q12hArm 5 Part A: Observational CohortArm 6 Part B: LUM 400 mg q12h/ IVA 250 mg q12hArm 7 Part B: Placebo - LUM 400 mg q12h/ IVA 250 mg q12h
Infective pulmonary exacerbation of cystic fibrosisInfections and infestations113/33561/178111/34059/1765/1915/5515/60
Distal intestinal obstruction syndromeGastrointestinal disorders2/3351/1786/34010/1760/190/550/60
Suicidal ideationPsychiatric disorders0/3350/1781/3400/1761/190/550/60
CardiomyopathyCardiac disorders0/3350/1780/3400/1761/190/550/60
HaemoptysisRespiratory, thoracic and mediastinal disorders17/3357/17810/3406/1761/190/552/60
InfluenzaInfections and infestations0/3352/1786/3403/1761/190/550/60
Lower respiratory tract infection bacterialInfections and infestations1/3350/1780/3400/1761/190/550/60
PneumoniaInfections and infestations6/3354/1785/3401/1760/190/550/60
Facial bones fractureInjury, poisoning and procedural complications0/3350/1780/3400/1760/191/550/60
Pulmonary function test decreasedInvestigations3/3351/1783/3400/1760/191/550/60
Most frequent other events
Showing 10 of 907
Most frequent other events
EventArm 1 Part A: LUM 600 mg qd/ IVA 250 mg q12hArm 2 Part A: Placebo - LUM 600 mg qd/ IVA 250 mg q12hArm 3 Part A: LUM 400 mg q12h/ IVA 250 mg q12hArm 4 Part A: Placebo - LUM 400 mg q12h/ IVA 250 mg q12hArm 5 Part A: Observational CohortArm 6 Part B: LUM 400 mg q12h/ IVA 250 mg q12hArm 7 Part B: Placebo - LUM 400 mg q12h/ IVA 250 mg q12h
Infective pulmonary exacerbation of cystic fibrosisInfections and infestations185/33592/178173/34091/176—18/5520/60
CoughRespiratory, thoracic and mediastinal disorders167/33592/178145/34082/176—18/5518/60
Respiration abnormalRespiratory, thoracic and mediastinal disorders39/33530/17834/34025/176—7/5521/60
Sputum increasedRespiratory, thoracic and mediastinal disorders75/33536/17879/34037/176—11/5518/60
DyspnoeaRespiratory, thoracic and mediastinal disorders52/33533/17853/34036/176—9/5513/60
HaemoptysisRespiratory, thoracic and mediastinal disorders61/33537/17868/34029/176—8/5510/60
NasopharyngitisInfections and infestations51/33531/17866/34027/176—6/556/60
PyrexiaGeneral disorders60/33527/17847/34031/176—6/558/60
HeadacheNervous system disorders58/33525/17856/34022/176—7/557/60
Blood creatine phosphokinase increasedInvestigations26/33523/17823/34015/176—5/5510/60

Baseline characteristics

Safety Set (study 105) included all participants who were exposed to any amount of study drug.

Age, Customized
Age, Customized(Participants)Arm 1 Part A: LUM 600 mg qd/ IVA 250 mg q12hq12h Arm 2 Part A: Placebo - LUM 600 mg qd/ IVA 250 mg q12hArm 3 Part A: LUM 400 mg q12h/ IVA 250 mg q12hArm 4 Part A: Placebo - LUM 400 mg q12h/ IVA 250 mg q12hArm 5 Part A: Observational CohortArm 6 Part B: LUM 400 mg q12h/ IVA 250 mg q12hArm 7 Part B: Placebo - LUM 400 mg q12h/ IVA 250 mg q12hTotal
12 years to less than 18 years93479447200283
Greater than or equal to 18 years242131246129175560880
Sex: Female, Male
Sex: Female, Male(Participants)Arm 1 Part A: LUM 600 mg qd/ IVA 250 mg q12hq12h Arm 2 Part A: Placebo - LUM 600 mg qd/ IVA 250 mg q12hArm 3 Part A: LUM 400 mg q12h/ IVA 250 mg q12hArm 4 Part A: Placebo - LUM 400 mg q12h/ IVA 250 mg q12hArm 5 Part A: Observational CohortArm 6 Part B: LUM 400 mg q12h/ IVA 250 mg q12hArm 7 Part B: Placebo - LUM 400 mg q12h/ IVA 250 mg q12hTotal
Female1668916486122531573
Male169891769073029590
08

Study locations

167 sites
  • Birmingham, Alabama, United States
  • Anchorage, Alaska, United States
  • Tucson, Arizona, United States
  • Little Rock, Arkansas, United States
  • La Jolla, California, United States
  • Loma Linda, California, United States
  • Longbeach, California, United States
  • Los Angeles, California, United States
  • Madera, California, United States
  • Oakland, California, United States
  • Palo Alto, California, United States
  • Sacramento, California, United States
  • Aurora, Colorado, United States
  • Denver, Colorado, United States
  • Hartford, Connecticut, United States
  • New Haven, Connecticut, United States
  • Altamonte Springs, Florida, United States
  • Hollywood, Florida, United States
  • Jacksonville, Florida, United States
  • Miami, Florida, United States
  • Orlando, Florida, United States
  • Tampa, Florida, United States
  • Atlanta, Georgia, United States
  • Boise, Idaho, United States
  • Chicago, Illinois, United States
  • Park Ridge, Illinois, United States
  • Peoria, Illinois, United States
  • Indianapolis, Indiana, United States
  • Iowa City, Iowa, United States
  • Kansas City, Kansas, United States
  • Lexington, Kentucky, United States
  • New Orleans, Louisiana, United States
  • South Portland, Maine, United States
  • Baltimore, Maryland, United States
  • Boston, Massachusetts, United States
  • Worcester, Massachusetts, United States
  • Ann Arbor, Michigan, United States
  • Detroit, Michigan, United States
  • Grand Rapids, Michigan, United States
  • Minneapolis, Minnesota, United States
  • Jackson, Mississippi, United States
  • Kansas City, Missouri, United States
  • St Louis, Missouri, United States
  • St. Louis, Missouri, United States
  • Omaha, Nebraska, United States
  • Bedford, New Hampshire, United States
  • Lebanon, New Hampshire, United States
  • Long Branch, New Jersey, United States
  • Morristown, New Jersey, United States
  • New Brunswick, New Jersey, United States
  • Albuquerque, New Mexico, United States
  • Albany, New York, United States
  • Buffalo, New York, United States
  • Lake Success, New York, United States
  • New York, New York, United States
  • Rochester, New York, United States
  • Syracuse, New York, United States
  • Valhalla, New York, United States
  • Chapel Hill, North Carolina, United States
  • Durham, North Carolina, United States
  • Akron, Ohio, United States
  • Cincinnati, Ohio, United States
  • Cleveland, Ohio, United States
  • Columbus, Ohio, United States
  • Dayton, Ohio, United States
  • Toledo, Ohio, United States
  • Oklahoma City, Oklahoma, United States
  • Portland, Oregon, United States
  • Hershey, Pennsylvania, United States
  • Philadelphia, Pennsylvania, United States
  • Pittsburgh, Pennsylvania, United States
  • Charelston, South Carolina, United States
  • Sioux Falls, South Dakota, United States
  • Knoxville, Tennessee, United States
  • Memphis, Tennessee, United States
  • Nashville, Tennessee, United States
  • Austin, Texas, United States
  • Dallas, Texas, United States
  • Fort Worth, Texas, United States
  • Houston, Texas, United States
  • San Antonio, Texas, United States
  • Tyler, Texas, United States
  • Salt Lake City, Utah, United States
  • Colchester, Vermont, United States
  • Charlottesville, Virginia, United States
  • Norfolk, Virginia, United States
  • Richmond, Virginia, United States
  • Seattle, Washington, United States
  • Spokane, Washington, United States
  • Morgantown, West Virginia, United States
  • Madison, Wisconsin, United States
  • Milwaukee, Wisconsin, United States
  • New Lambton Heights, New South Wales, Australia
  • Westmead, New South Wales, Australia
  • Adelaide, Queensland, Australia
  • Chermside, Queensland, Australia
  • Herston, Queensland, Australia
  • South Brisbane, Queensland, Australia
  • Nedlands, Australia
  • Subiaco, Australia

Showing the first 100 of 167 sites across 15 countries.

09

References and documents

Publications

  • Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3. PubMed 33331662 ↗
  • Konstan MW, McKone EF, Moss RB, Marigowda G, Tian S, Waltz D, Huang X, Lubarsky B, Rubin J, Millar SJ, Pasta DJ, Mayer-Hamblett N, Goss CH, Morgan W, Sawicki GS. Assessment of safety and efficacy of long-term treatment with combination lumacaftor and ivacaftor therapy in patients with cystic fibrosis homozygous for the F508del-CFTR mutation (PROGRESS): a phase 3, extension study. Lancet Respir Med. 2017 Feb;5(2):107-118. doi: 10.1016/S2213-2600(16)30427-1. Epub 2016 Dec 21. PubMed 28011037 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 12, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01931839
Lead sponsor
Vertex Pharmaceuticals Incorporated
Responsible party
Sponsor
First posted
Aug 29, 2013
Start date
Oct 2013
Primary completion
Apr 2016
Completion
Apr 2016
Results posted
May 12, 2017
Last update
May 12, 2017

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Apr 2017. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Cystic Fibrosis→

Other studies from this sponsor

Vertex Pharmaceuticals Incorporated

Start the discussion