Cystic Fibrosis
Conditions
Brief summary
This study will evaluate the long-term safety and tolerability of VX-659 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous or heterozygous for the F508del mutation.
Interventions
DRUGVX-659/TEZ/IVA
Fixed-dose combination tablets for oral administration qd in the morning.
DRUGIVA
IVA tablet qd in the evening.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Completed study drug treatment in a parent study; or had study drug interruption(s) in a parent study but completed study visits up to the last scheduled visit of the Treatment Period in the parent study.
Exclusion criteria
* History of drug intolerance in a parent study that would pose an additional risk to the subject in the opinion of the investigator. * Current participation in an investigational drug trial (other than a parent study) Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | From Day 1 up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First in the Current Study 659-105 (up to Week 100) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in ppFEV1 for Participants From the Parent Study 659-103 | From Baseline at Week 72 (Study 659-105) | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline. |
| Absolute Change in Sweat Chloride (SwCl) for Participants From the Parent Study 659-102 | From Baseline at Week 24 (Study 659-105) | Sweat samples were collected using an approved collection device. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline. |
| Absolute Change in SwCl for Participants From the Parent Study 659-103 | From Baseline at Week 24 (Study 659-105) | Sweat samples were collected using an approved collection device. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline. |
| Number of Pulmonary Exacerbations (PEx) for Participants From the Parent Study 659-102 | From Baseline up to Week 96 (Study 659-105) | PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-102 or/and VX-659/TEZ/IVA in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline except for Placebo - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline. |
| Number of PEx for Participants From the Parent Study 659-103 | From Baseline up to Week 96 (Study 659-105) | PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The analysis was planned to be reported for overall participants from the parent study 659-103, that is combined for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-103 or/and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline except for TEZ/IVA - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline. |
| Number of Participants With at Least One PEx for Participants From the Parent Study 659-102 | From Baseline up to Week 96 (Study 659-105) | PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The time-to-first-PEx data were planned to be estimated using the Kaplan-Meier (KM) method. However, because way less than 50% of participants had events, median time-to-first event data were not estimable. Instead, the number of participants with at least one PEx event was assessed and reported separately for those in Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and the VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-102 or/and VX-659/TEZ/IVA in the current study 659-105). Baseline was defined as the parent study baseline except for Placebo - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline. |
| Number of Participants With at Least One PEx for Participants From the Parent Study 659-103 | From Baseline up to Week 96 (Study 659-105) | PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The time-to-first-PEx data were planned to be estimated using the KM method. However, because way less than 50% of participants had events, median time-to-first-event data were not estimable. Instead, the number of participants with at least one PEx event was assessed and reported for all participants from the parent study 659-103, that is combined for those in the TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and the VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-103 or/and in the current study 659-105). Baseline was defined as the parent study baseline except for TEZ/IVA - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline. |
| Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for Participants From the Parent Study 659-102 | From Baseline at Week 72 (Study 659-105) | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline. |
| Absolute Change in BMI for Participants From the Parent Study 659-103 | From Baseline at Week 72 (Study 659-105) | BMI was defined as weight in kg divided by squared height in meters (m\^2). The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline. |
| Absolute Change in BMI Z-score for Participants From the Parent Study 659-102 (Participants <=20 Years Old at Parent Study Baseline) | From Baseline at Week 60 (Study 659-105) | BMI was defined as weight in kg divided by squared height in meters (m\^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline. |
| Absolute Change in BMI Z-score for Participants From The Parent Study 659-103 (Participants <=20 Years Old at Parent Study Baseline) | From Baseline at Week 60 (Study 659-105) | BMI was defined as weight in kg divided by squared height in meters (m\^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline. |
| Absolute Change in Body Weight for Participants From the Parent Study 659-102 | From Baseline at Week 72 (Study 659-105) | The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline. |
| Absolute Change in Body Weight for Participants From the Parent Study 659-103 | From Baseline at Week 72 (Study 659-105) | The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline. |
| Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for Participants From the Parent Study 659-102 | From Baseline at Week 72 (Study 659-105) | 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. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline. |
| Absolute Change in CFQ-R Respiratory Domain Score for Participants From the Parent Study 659-103 | From Baseline at Week 72 (Study 659-105) | 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. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline. |
| Absolute Change in Body Mass Index (BMI) for Participants From the Parent Study 659-102 | From Baseline at Week 72 (Study 659-105) | BMI was defined as weight in kilograms (kg) divided by squared height in meters (m\^2). The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline. |
Countries
Australia, Canada, Denmark, Germany, Ireland, Israel, Poland, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
A total of 484 participants were enrolled from the parent studies VX17-659-102 (Study 659-102; NCT03447249) and VX17-659-103 (Study 659-103; NCT03460990). Out of which, 3 participants were enrolled but never dosed in the current study VX17-659-105 (Study 659-105). Therefore, the below results are presented for 481 participants.
Pre-assignment details
This study was conducted in cystic fibrosis (CF) participants aged 12 years or older who participated in parent studies 659-102 or 659-103. Eligible participants from the parent studies were enrolled in the current study 659-105.
Participants by arm
| Arm | Count |
|---|---|
| VX-659/TEZ/IVA TC Participants from parent studies 659-102 or 659-103 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105. | 481 |
| Total | 481 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Commercial Drug is Available for Participant | 9 |
| Overall Study | Death | 2 |
| Overall Study | Other | 4 |
| Overall Study | Study Termination by Sponsor | 455 |
| Overall Study | Withdrawal of Consent (not due to AE) | 2 |
Baseline characteristics
| Characteristic | VX-659/TEZ/IVA TC |
|---|---|
| Age, Continuous | 26.9 years STANDARD_DEVIATION 9.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 462 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 474 Participants |
| Sex: Female, Male Female | 219 Participants |
| Sex: Female, Male Male | 262 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 481 |
| other Total, other adverse events | 446 / 481 |
| serious Total, serious adverse events | 99 / 481 |
Outcome results
Primary
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From Day 1 up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First in the Current Study 659-105 (up to Week 100)
Population: Open label safety set (OL-SS) included all participants who received at least 1 dose of study drug in the current study 659-105.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VX-659/TEZ/IVA TC | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 470 participants |
| VX-659/TEZ/IVA TC | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 99 participants |
Secondary
Absolute Change in BMI for Participants From the Parent Study 659-103
BMI was defined as weight in kg divided by squared height in meters (m\^2). The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Week 72 (Study 659-105)
Population: OL-FAS included all rolled over participants from the parent study 659-103 who received at least 1 dose of study drug in the current study 659-105. Here, number analyzed signifies participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VX-659/TEZ/IVA TC | Absolute Change in BMI for Participants From the Parent Study 659-103 | TEZ/IVA - VX-659/TEZ/IVA | 1.16 kg/m^2 | Standard Deviation 1.68 |
| VX-659/TEZ/IVA TC | Absolute Change in BMI for Participants From the Parent Study 659-103 | VX-659/TEZ/IVA - VX-659/TEZ/IVA | 0.90 kg/m^2 | Standard Deviation 1.52 |
Secondary
Absolute Change in BMI Z-score for Participants From the Parent Study 659-102 (Participants <=20 Years Old at Parent Study Baseline)
BMI was defined as weight in kg divided by squared height in meters (m\^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Week 60 (Study 659-105)
Population: OL-FAS included all rolled over participants from the parent study 659-102 who were \<=20 years old at parent study baseline and received at least 1 dose of study drug in the current study 659-105. Here, number analyzed signifies participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VX-659/TEZ/IVA TC | Absolute Change in BMI Z-score for Participants From the Parent Study 659-102 (Participants <=20 Years Old at Parent Study Baseline) | Placebo - VX-659/TEZ/IVA | 0.22 z-score | Standard Deviation 0.59 |
| VX-659/TEZ/IVA TC | Absolute Change in BMI Z-score for Participants From the Parent Study 659-102 (Participants <=20 Years Old at Parent Study Baseline) | VX-659/TEZ/IVA - VX-659/TEZ/IVA | 0.10 z-score | Standard Deviation 0.44 |
Secondary
Absolute Change in BMI Z-score for Participants From The Parent Study 659-103 (Participants <=20 Years Old at Parent Study Baseline)
BMI was defined as weight in kg divided by squared height in meters (m\^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Week 60 (Study 659-105)
Population: OL-FAS included all rolled over participants from the parent study 659-103 who were \<=20 years old at parent study baseline and received at least 1 dose of study drug in the current study 659-105. Here, number analyzed signifies participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| VX-659/TEZ/IVA TC | Absolute Change in BMI Z-score for Participants From The Parent Study 659-103 (Participants <=20 Years Old at Parent Study Baseline) | TEZ/IVA - VX-659/TEZ/IVA | NA z-score |
| VX-659/TEZ/IVA TC | Absolute Change in BMI Z-score for Participants From The Parent Study 659-103 (Participants <=20 Years Old at Parent Study Baseline) | VX-659/TEZ/IVA - VX-659/TEZ/IVA | NA z-score |
Secondary
Absolute Change in Body Mass Index (BMI) for Participants From the Parent Study 659-102
BMI was defined as weight in kilograms (kg) divided by squared height in meters (m\^2). The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Week 72 (Study 659-105)
Population: OL-FAS included all rolled over participants from the parent study 659-102 who received at least 1 dose of study drug in the current study 659-105. Here, number analyzed signifies participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VX-659/TEZ/IVA TC | Absolute Change in Body Mass Index (BMI) for Participants From the Parent Study 659-102 | Placebo - VX-659/TEZ/IVA | 1.55 kilogram per meter square (kg/m^2) | Standard Deviation 1.35 |
| VX-659/TEZ/IVA TC | Absolute Change in Body Mass Index (BMI) for Participants From the Parent Study 659-102 | VX-659/TEZ/IVA - VX-659/TEZ/IVA | 1.43 kilogram per meter square (kg/m^2) | Standard Deviation 1.94 |
Secondary
Absolute Change in Body Weight for Participants From the Parent Study 659-102
The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Week 72 (Study 659-105)
Population: OL-FAS included all rolled over participants from the parent study 659-102 who received at least 1 dose of study drug in the current study 659-105. Here, number analyzed signifies participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VX-659/TEZ/IVA TC | Absolute Change in Body Weight for Participants From the Parent Study 659-102 | Placebo - VX-659/TEZ/IVA | 4.8 kg | Standard Deviation 4.4 |
| VX-659/TEZ/IVA TC | Absolute Change in Body Weight for Participants From the Parent Study 659-102 | VX-659/TEZ/IVA - VX-659/TEZ/IVA | 4.3 kg | Standard Deviation 5.6 |
Secondary
Absolute Change in Body Weight for Participants From the Parent Study 659-103
The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Week 72 (Study 659-105)
Population: OL-FAS included all rolled over participants from the parent study 659-103 who received at least 1 dose of study drug in the current study 659-105. Here, number analyzed signifies participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VX-659/TEZ/IVA TC | Absolute Change in Body Weight for Participants From the Parent Study 659-103 | TEZ/IVA - VX-659/TEZ/IVA | 3.7 kg | Standard Deviation 4.9 |
| VX-659/TEZ/IVA TC | Absolute Change in Body Weight for Participants From the Parent Study 659-103 | VX-659/TEZ/IVA - VX-659/TEZ/IVA | 3.2 kg | Standard Deviation 5 |
Secondary
Absolute Change in CFQ-R Respiratory Domain Score for Participants From the Parent Study 659-103
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. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Week 72 (Study 659-105)
Population: OL-FAS included all rolled over participants from the parent study 659-103 who received at least 1 dose of study drug in the current study 659-105. Here, number analyzed signifies participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VX-659/TEZ/IVA TC | Absolute Change in CFQ-R Respiratory Domain Score for Participants From the Parent Study 659-103 | TEZ/IVA - VX-659/TEZ/IVA | 17.1 units on a scale | Standard Deviation 18.2 |
| VX-659/TEZ/IVA TC | Absolute Change in CFQ-R Respiratory Domain Score for Participants From the Parent Study 659-103 | VX-659/TEZ/IVA - VX-659/TEZ/IVA | 16.9 units on a scale | Standard Deviation 17.3 |
Secondary
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for Participants From the Parent Study 659-102
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. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Week 72 (Study 659-105)
Population: OL-FAS included all rolled over participants from the parent study 659-102 who received at least 1 dose of study drug in the current study 659-105. Here, number analyzed signifies participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VX-659/TEZ/IVA TC | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for Participants From the Parent Study 659-102 | Placebo - VX-659/TEZ/IVA | 16.7 units on a scale | Standard Deviation 18.7 |
| VX-659/TEZ/IVA TC | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for Participants From the Parent Study 659-102 | VX-659/TEZ/IVA - VX-659/TEZ/IVA | 19.7 units on a scale | Standard Deviation 17.4 |
Secondary
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for Participants From the Parent Study 659-102
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Week 72 (Study 659-105)
Population: Open label full analysis set (OL-FAS) included all rolled over participants from the parent study 659-102 who received at least 1 dose of study drug in the current study 659-105. Here, number analyzed signifies participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VX-659/TEZ/IVA TC | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for Participants From the Parent Study 659-102 | Placebo - VX-659/TEZ/IVA | 14.2 percentage points | Standard Deviation 7.8 |
| VX-659/TEZ/IVA TC | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for Participants From the Parent Study 659-102 | VX-659/TEZ/IVA - VX-659/TEZ/IVA | 10.3 percentage points | Standard Deviation 9.3 |
Secondary
Absolute Change in ppFEV1 for Participants From the Parent Study 659-103
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Week 72 (Study 659-105)
Population: OL-FAS included all rolled over participants from the parent study 659-103 who received at least 1 dose of study drug in the current study 659-105. Here, number analyzed signifies participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VX-659/TEZ/IVA TC | Absolute Change in ppFEV1 for Participants From the Parent Study 659-103 | TEZ/IVA - VX-659/TEZ/IVA | 15.1 percentage points | Standard Deviation 11.9 |
| VX-659/TEZ/IVA TC | Absolute Change in ppFEV1 for Participants From the Parent Study 659-103 | VX-659/TEZ/IVA - VX-659/TEZ/IVA | 11.5 percentage points | Standard Deviation 9.8 |
Secondary
Absolute Change in SwCl for Participants From the Parent Study 659-103
Sweat samples were collected using an approved collection device. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Week 24 (Study 659-105)
Population: OL-FAS included all rolled over participants from the parent study 659-103 who received at least 1 dose of study drug in the current study 659-105. Here, number analyzed signifies participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VX-659/TEZ/IVA TC | Absolute Change in SwCl for Participants From the Parent Study 659-103 | TEZ/IVA - VX-659/TEZ/IVA | -45.7 mmol/L | Standard Deviation 16.8 |
| VX-659/TEZ/IVA TC | Absolute Change in SwCl for Participants From the Parent Study 659-103 | VX-659/TEZ/IVA - VX-659/TEZ/IVA | -53.5 mmol/L | Standard Deviation 16.2 |
Secondary
Absolute Change in Sweat Chloride (SwCl) for Participants From the Parent Study 659-102
Sweat samples were collected using an approved collection device. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Week 24 (Study 659-105)
Population: OL-FAS included all rolled over participants from the parent study 659-102 who received at least 1 dose of study drug in the current study 659-105. Here, number analyzed signifies participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VX-659/TEZ/IVA TC | Absolute Change in Sweat Chloride (SwCl) for Participants From the Parent Study 659-102 | Placebo - VX-659/TEZ/IVA | -48.9 millimole per liter (mmol/L) | Standard Deviation 20.4 |
| VX-659/TEZ/IVA TC | Absolute Change in Sweat Chloride (SwCl) for Participants From the Parent Study 659-102 | VX-659/TEZ/IVA - VX-659/TEZ/IVA | -49.7 millimole per liter (mmol/L) | Standard Deviation 20.1 |
Secondary
Number of Participants With at Least One PEx for Participants From the Parent Study 659-102
PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The time-to-first-PEx data were planned to be estimated using the Kaplan-Meier (KM) method. However, because way less than 50% of participants had events, median time-to-first event data were not estimable. Instead, the number of participants with at least one PEx event was assessed and reported separately for those in Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and the VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-102 or/and VX-659/TEZ/IVA in the current study 659-105). Baseline was defined as the parent study baseline except for Placebo - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.
Time frame: From Baseline up to Week 96 (Study 659-105)
Population: The cumulative TC efficacy set for PEx analysis included all participants who were randomized to VX-659/TEZ/IVA arm and received at least one dose of study drug during the parent study 659-102 and/or received at least one dose of study drug during the current study 659-105. Here, number analyzed signifies participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VX-659/TEZ/IVA TC | Number of Participants With at Least One PEx for Participants From the Parent Study 659-102 | VX-659/TEZ/IVA - VX-659/TEZ/IVA | 52 participants |
| VX-659/TEZ/IVA TC | Number of Participants With at Least One PEx for Participants From the Parent Study 659-102 | Placebo - VX-659/TEZ/IVA | 43 participants |
Secondary
Number of Participants With at Least One PEx for Participants From the Parent Study 659-103
PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The time-to-first-PEx data were planned to be estimated using the KM method. However, because way less than 50% of participants had events, median time-to-first-event data were not estimable. Instead, the number of participants with at least one PEx event was assessed and reported for all participants from the parent study 659-103, that is combined for those in the TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and the VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-103 or/and in the current study 659-105). Baseline was defined as the parent study baseline except for TEZ/IVA - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.
Time frame: From Baseline up to Week 96 (Study 659-105)
Population: The cumulative TC efficacy set for PEx analysis included all participants who were randomized to VX-659/TEZ/IVA arm and received at least one dose of study drug during the parent study 659-103 and/or received at least one dose of study drug during the current study 659-105.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VX-659/TEZ/IVA TC | Number of Participants With at Least One PEx for Participants From the Parent Study 659-103 | 28 participants |
Secondary
Number of PEx for Participants From the Parent Study 659-103
PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The analysis was planned to be reported for overall participants from the parent study 659-103, that is combined for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-103 or/and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline except for TEZ/IVA - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.
Time frame: From Baseline up to Week 96 (Study 659-105)
Population: The cumulative TC efficacy set for PEx analysis included all participants who were randomized to VX-659/TEZ/IVA arm and received at least one dose of study drug during the parent study 659-103 and/or received at least one dose of study drug during the current study 659-105.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VX-659/TEZ/IVA TC | Number of PEx for Participants From the Parent Study 659-103 | 39 PEx events |
Secondary
Number of Pulmonary Exacerbations (PEx) for Participants From the Parent Study 659-102
PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-102 or/and VX-659/TEZ/IVA in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline except for Placebo - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.
Time frame: From Baseline up to Week 96 (Study 659-105)
Population: The cumulative TC efficacy set for PEx analysis included all participants who were randomized to VX-659/TEZ/IVA arm and received at least one dose of study drug during the parent study 659-102 and/or received at least one dose of study drug during the current study 659-105. Here, number analyzed signifies participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VX-659/TEZ/IVA TC | Number of Pulmonary Exacerbations (PEx) for Participants From the Parent Study 659-102 | Placebo - VX-659/TEZ/IVA | 60 PEx events |
| VX-659/TEZ/IVA TC | Number of Pulmonary Exacerbations (PEx) for Participants From the Parent Study 659-102 | VX-659/TEZ/IVA - VX-659/TEZ/IVA | 84 PEx events |