Cystic Fibrosis
Conditions
Brief summary
This is a Phase 3, multicenter, open-label, 3-part rollover study in subjects with CF who are homozygous or heterozygous for the F508del-CFTR mutation and who participated in studies VX13-661-103 (Study 103, NCT02070744), VX14-661-106 (Study 106, NCT02347657), VX14-661-107 (Study 107, NCT02516410), VX14-661-108 (Study 108, NCT02392234), VX14-661-109 (Study 109, NCT02412111), VX14-661-111 (Study 111, NCT02508207), VX15-661-112 (NCT02730208), and VX16-661-114 (NCT03150719). The study is designed to evaluate the safety and efficacy of long-term treatment of VX-661 in combination with ivacaftor.
Interventions
DRUGTEZ/IVA
Fixed dose tablet for oral administration.
DRUGIVA
Tablet for oral administration.
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
Part A: * Participants entering the Treatment Cohort must meet all of the following criteria: * Elect to enroll in the Treatment Cohort * Completed study drug Treatment Period in a parent study (NCT02070744, NCT02347657, NCT02516410, NCT02392234, NCT02412111) or study drug treatment and the Safety Follow up Visit for participants from NCT02508207. * Willing to remain on a stable CF regimen through the Safety Follow-up Visit. * Participants re-enrolling in the Part A Treatment Cohort must meet all of the following criteria: * Previously received at least 4 weeks of study drug before discontinuing in Part A of Study NCT02565914 to participate in another qualified Vertex study. * Completed the last required visit of another qualified Vertex study before or during the Returning Visit in Part A Study NCT02565914. * Participants entering the Part A Observational Cohort must meet the following criteria: * \<18 years of age (age on the date of informed consent/assent in the parent study) * Completed study drug Treatment Period in a parent study or study drug treatment and the Safety Follow up Visit for subjects from NCT02508207, but do not elect to enroll in the NCT02565914 Treatment Cohort; or * Received at least 4 weeks of study drug treatment and completed visits up to the last scheduled visit of the Treatment Period of a parent study (and the Safety Follow up Visit for participants from NCT02508207), but do not meet eligibility criteria for enrollment into the Treatment Cohort Part B: Participants who meet all of the following inclusion criteria will be eligible for Part B. * Did not withdraw consent from the parent study or Part A of Study NCT02565914. * Completed study drug treatment during the Treatment Period in Part A of - Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit of Study NCT02565914. Participants re enrolling in Part B must meet all of the following criteria: * Previously received at least 4 weeks of study drug before discontinuing Study NCT02565914 to participate in another qualified Vertex study, which is defined as a Vertex study of investigational CFTR modulators that allows participation of participants in Study NCT02565914. * Completed the last required visit of another qualified Vertex study before or during the Returning Visit in Part B. * Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit in Part B. Part C: * Participants who meet all of the following inclusion criteria will be eligible for Part C. * Did not withdraw consent from Part B of Study NCT02565914. * Completed study drug treatment during Part B of NCT02565914. * Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit of Part C.
Exclusion criteria
* History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the subject. * Pregnant and nursing females. * Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements. * History of drug intolerance in the parent study that would pose an additional risk to the subject. * Participation in an investigational drug trial (including studies investigating VX-661/ivacaftor or lumacaftor/ivacaftor) other than the parent studies of NCT02565914 or other eligible Vertex studies investigating VX-661 in combination with ivacaftor, or use of a commercially available CFTR modulator. Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs | Day 1 up to Week 100 |
| Part C: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 up to Week 196 |
| Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 up to Week 100 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set | From Baseline at Study 110 Week 96 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 111 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 111 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline. |
| Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set | From Baseline at Study 110 Week 96 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline. |
| Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set | From Baseline at Study 110 Week 96 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline. |
| Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set | From Baseline at Study 110 Week 96 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline. |
| Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set | From Baseline at Study 110 Week 96 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 111 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 111 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline. |
| Part A: Number of Pulmonary Exacerbation (PEx) Events for 106/110 PEx Analysis Set | From Baseline up to Study 110 Week 96 | Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline. |
| Part A: Number of Pulmonary Exacerbation (PEx) Events for 108/110 PEx Analysis Set | From Baseline up to Week 96 | Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline. |
| Part A: Absolute Change in Body Mass Index (BMI) for 106/110 Efficacy Set | From Baseline at Study 110 Week 96 | BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2). Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline. |
| Part A: Absolute Change in Body Mass Index (BMI) for 108/110 Efficacy Set | From Baseline at Study 110 Week 96 | BMI was defined as weight in kg divided by height in square meter (m\^2). Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline. |
| Part A: Absolute Change in Body Mass Index (BMI) for 103/110 Efficacy Set | From Baseline at Study 110 Week 96 | BMI was defined as weight in kg divided by height in square meter (m\^2). Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline. |
| Part A: Absolute Change in Body Mass Index (BMI) for Study 111/110 Efficacy Set | From Baseline at Study 110 Week 96 | BMI was defined as weight in kg divided by height in square meter (m\^2). Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 111 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 111 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline. |
| Part A: Absolute Change in BMI Z-score for 106/110 Efficacy Set | From Baseline at Study 110 Week 96 | The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline. |
| Part A: Absolute Change in BMI Z-score for 108/110 Efficacy Set | From Baseline at Study 110 Week 96 | The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline. |
| Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 106/110 Efficacy Set | From Baseline at Study 110 Week 96 | The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline. |
| Part A: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 108/110 Efficacy Set | From Baseline at Study 110 Week 96 | The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline. |
| Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set | From Baseline at Study 110 Week 96 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline. |
| Part A: Absolute Change in Body Weight for Study 106/110 Efficacy Set | From Baseline at Study 110 Week 96 | Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline. |
| Part A: Absolute Change in Body Weight for 108/110 Efficacy Set | From Baseline at Study 110 Week 96 | Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline. |
| Part A: Absolute Change in Body Weight for 103/110 Efficacy Set | From Baseline at Study 110 Week 96 | Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline. |
| Part A: Absolute Change in Body Weight for 111/110 Efficacy Set | From Baseline at Study 110 Week 96 | Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 111 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 111 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline. |
| Part A: Absolute Change in Body Weight Z-score for 106/110 Efficacy Set | From Baseline at Study 110 Week 96 | The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline. |
| Part A: Absolute Change in Body Weight Z-score for 108/110 Efficacy Set | From Baseline at Study 110 Week 96 | The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline. |
| Part A: Absolute Change in Height Z-score for 106/110 Efficacy Set | From Baseline at Study 110 Week 96 | The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline. |
| Part A: Absolute Change in Height Z-score for 108/110 Efficacy Set | From Baseline at Study 110 Week 96 | The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline. |
| Part A: Time-to-first Pulmonary Exacerbation (PEx) for 106/110 PEx Analysis Set | 96 weeks | Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. |
| Part A: Time-to-first Pulmonary Exacerbation (PEx) for 108/110 PEx Analysis Set | 96 weeks | Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. |
| Part A: Plasma Concentrations of TEZ, TEZ Metabolite (M1-TEZ), Ivacaftor (IVA) and Ivacaftor Metabolite (M1-IVA) | Week 24 | — |
| Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | From Baseline at Study 110 Week 96 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
| Part B: Absolute Change in Body Mass Index (BMI) | From Baseline at Week 96 | BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2). |
| Part B: Absolute Change in BMI Z-score | From Baseline at Week 96 | The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. |
| Part B: Number of Pulmonary Exacerbation (PEx) Events | From Baseline up to Week 96 | Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. |
| Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/110 Efficacy Set | From Baseline at Study 110 Week 96 | The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline. |
| Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set | From Baseline at Study 110 Week 96 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline. |
| Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set | From Baseline at Study 110 Week 96 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline. |
Countries
Australia, Austria, Belgium, Canada, Denmark, France, Germany, Ireland, Israel, Italy, Netherlands, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
This study consisted of 3 parts: Parts A, B, and C.
Pre-assignment details
A total 1131 participants enrolled in the study (1044 in Part A, 464 in Part B and 204 in Part C).
Participants by arm
| Arm | Count |
|---|---|
| TEZ/IVA Part A: Participants who received either TEZ/IVA, IVA monotherapy or Placebo in parent studies 103,106,107,108,109 and 111 were administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks.
Part B: Participants who received either TEZ/IVA, IVA monotherapy or Placebo in parent studies 106, 108, 109, 112 and 114 were administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks.
Part C: Participants who received TEZ/IVA, IVA monotherapy or Placebo in parent studies 106, 108, and 114 were administered TEZ 100 mg/IVA 150 mg fixed dose tablet in the morning and IVA 150 mg mono tablet in the evening for 192 weeks. | 1,131 |
| Total | 1,131 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Part A (Up to 96 Weeks) | Adverse Event | 17 |
| Part A (Up to 96 Weeks) | Commercial drug available | 5 |
| Part A (Up to 96 Weeks) | Death (not treatment emergent) | 1 |
| Part A (Up to 96 Weeks) | Enrolled, but did not receive study drug | 2 |
| Part A (Up to 96 Weeks) | Lost to Follow-up | 12 |
| Part A (Up to 96 Weeks) | Other | 18 |
| Part A (Up to 96 Weeks) | Other noncompliance | 6 |
| Part A (Up to 96 Weeks) | Parent study termination by sponsor | 1 |
| Part A (Up to 96 Weeks) | Physician Decision | 6 |
| Part A (Up to 96 Weeks) | Withdrawal of consent (not due to AE) | 25 |
| Part B (Up to 96 Weeks) | Adverse Event | 4 |
| Part B (Up to 96 Weeks) | Commercial drug is available for participant | 196 |
| Part B (Up to 96 Weeks) | Enrolled, but did not receive study drug | 1 |
| Part B (Up to 96 Weeks) | Other | 1 |
| Part B (Up to 96 Weeks) | Physician Decision | 1 |
| Part B (Up to 96 Weeks) | Rolled over into another study | 25 |
| Part B (Up to 96 Weeks) | Sponsor Decision | 2 |
| Part B (Up to 96 Weeks) | Withdrawal of consent (not due to AE) | 6 |
| Part C (Up to 192 Weeks) | Adverse Event | 1 |
| Part C (Up to 192 Weeks) | Commercial drug is available for participant | 174 |
| Part C (Up to 192 Weeks) | Other non-compliance | 2 |
| Part C (Up to 192 Weeks) | Physician Decision | 5 |
| Part C (Up to 192 Weeks) | Rolled over into another study | 11 |
| Part C (Up to 192 Weeks) | Withdrawal of consent (not due to AE) | 4 |
Baseline characteristics
| Characteristic | TEZ/IVA |
|---|---|
| Age, Continuous Part A | 29.13 years STANDARD_DEVIATION 12 |
| Age, Continuous Part B | 29.61 years STANDARD_DEVIATION 11.89 |
| Age, Continuous Part C | 29.60 years STANDARD_DEVIATION 11.68 |
| Race/Ethnicity, Customized Part A American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Part A Asian | 2 Participants |
| Race/Ethnicity, Customized Part A Black or African American | 7 Participants |
| Race/Ethnicity, Customized Part A Hispanic or Latino | 25 Participants |
| Race/Ethnicity, Customized Part A Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Part A Not collected per local regulations | 17 Participants |
| Race/Ethnicity, Customized Part A Not Hispanic or Latino | 1002 Participants |
| Race/Ethnicity, Customized Part A Other | 6 Participants |
| Race/Ethnicity, Customized Part A White | 1017 Participants |
| Race/Ethnicity, Customized Part B American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Part B Asian | 2 Participants |
| Race/Ethnicity, Customized Part B Black or African American | 1 Participants |
| Race/Ethnicity, Customized Part B Hispanic or Latino | 6 Participants |
| Race/Ethnicity, Customized Part B Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Part B Not collected per local regulations | 21 Participants |
| Race/Ethnicity, Customized Part B Not Hispanic or Latino | 437 Participants |
| Race/Ethnicity, Customized Part B Other | 1 Participants |
| Race/Ethnicity, Customized Part B White | 447 Participants |
| Race/Ethnicity, Customized Part C American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Part C Asian | 1 Participants |
| Race/Ethnicity, Customized Part C Black or African American | 0 Participants |
| Race/Ethnicity, Customized Part C Hispanic or Latino | 5 Participants |
| Race/Ethnicity, Customized Part C Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Part C Not collected per local regulations | 15 Participants |
| Race/Ethnicity, Customized Part C Not Hispanic or Latino | 184 Participants |
| Race/Ethnicity, Customized Part C Other | 0 Participants |
| Race/Ethnicity, Customized Part C White | 193 Participants |
| Sex: Female, Male Part A Female | 505 Participants |
| Sex: Female, Male Part A Male | 539 Participants |
| Sex: Female, Male Part B Female | 221 Participants |
| Sex: Female, Male Part B Male | 243 Participants |
| Sex: Female, Male Part C Female | 89 Participants |
| Sex: Female, Male Part C Male | 115 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1,042 | 0 / 463 | 0 / 204 |
| other Total, other adverse events | 938 / 1,042 | 391 / 463 | 149 / 204 |
| serious Total, serious adverse events | 351 / 1,042 | 136 / 463 | 44 / 204 |
Outcome results
Primary
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Week 100
Population: Safety Set was defined as all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 995 Participants |
| Part A: TEZ/IVA | Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 351 Participants |
Primary
Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs
Time frame: Day 1 up to Week 100
Population: Safety set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: TEZ/IVA | Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs | Participants with TEAEs | 427 Participants |
| Part A: TEZ/IVA | Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs | Participants with SAEs | 136 Participants |
Primary
Part C: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Week 196
Population: Safety set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: TEZ/IVA | Part C: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 168 Participants |
| Part A: TEZ/IVA | Part C: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 44 Participants |
Secondary
Part A: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 108/110 Efficacy Set
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 108/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 108 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 108/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 10.3 units on a scale |
| Part A: TEZ/IVA | Part A: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 108/110 Efficacy Set | IVA-TEZ/IVA: Change at Week 96 | 11.2 units on a scale |
| Part A: TEZ/IVA | Part A: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 108/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | 13.8 units on a scale |
Secondary
Part A: Absolute Change in BMI Z-score for 106/110 Efficacy Set
The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 106/110 efficacy set included all enrolled participants \<20 years of age at Screening who received at least 1 dose of study drug in Part A and rolled over from parent study 106 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in BMI Z-score for 106/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 0.10 z-score |
| Part A: TEZ/IVA | Part A: Absolute Change in BMI Z-score for 106/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | -0.14 z-score |
Secondary
Part A: Absolute Change in BMI Z-score for 108/110 Efficacy Set
The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 108/110 efficacy set included all enrolled participants \<20 years of age at Screening who received at least 1 dose of study drug in Part A and rolled over from parent study 108 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in BMI Z-score for 108/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 0.11 z-score |
| Part A: TEZ/IVA | Part A: Absolute Change in BMI Z-score for 108/110 Efficacy Set | IVA-TEZ/IVA: Change at Week 96 | 0.07 z-score |
| Part A: TEZ/IVA | Part A: Absolute Change in BMI Z-score for 108/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | 0.30 z-score |
Secondary
Part A: Absolute Change in Body Mass Index (BMI) for 103/110 Efficacy Set
BMI was defined as weight in kg divided by height in square meter (m\^2). Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 103/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 103 and had pre-defined CFTR genotypes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in Body Mass Index (BMI) for 103/110 Efficacy Set | 1.38 kg/m^2 | Standard Deviation 1.73 |
Secondary
Part A: Absolute Change in Body Mass Index (BMI) for 106/110 Efficacy Set
BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2). Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 106/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 106 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in Body Mass Index (BMI) for 106/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 0.47 kg/m^2 |
| Part A: TEZ/IVA | Part A: Absolute Change in Body Mass Index (BMI) for 106/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | 0.38 kg/m^2 |
Secondary
Part A: Absolute Change in Body Mass Index (BMI) for 108/110 Efficacy Set
BMI was defined as weight in kg divided by height in square meter (m\^2). Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 108/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 108 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in Body Mass Index (BMI) for 108/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 1.07 kg/m^2 |
| Part A: TEZ/IVA | Part A: Absolute Change in Body Mass Index (BMI) for 108/110 Efficacy Set | IVA-TEZ/IVA: Change at Week 96 | 0.96 kg/m^2 |
| Part A: TEZ/IVA | Part A: Absolute Change in Body Mass Index (BMI) for 108/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | 1.05 kg/m^2 |
Secondary
Part A: Absolute Change in Body Mass Index (BMI) for Study 111/110 Efficacy Set
BMI was defined as weight in kg divided by height in square meter (m\^2). Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 111 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 111 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 111/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 111 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in Body Mass Index (BMI) for Study 111/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 1.59 kg/m^2 | Standard Deviation 2.08 |
| Part A: TEZ/IVA | Part A: Absolute Change in Body Mass Index (BMI) for Study 111/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | 0.26 kg/m^2 | Standard Deviation 0.88 |
Secondary
Part A: Absolute Change in Body Weight for 103/110 Efficacy Set
Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 103/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 103 and had pre-defined CFTR genotypes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in Body Weight for 103/110 Efficacy Set | 4.0 kg | Standard Deviation 5 |
Secondary
Part A: Absolute Change in Body Weight for 108/110 Efficacy Set
Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 108/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 108 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in Body Weight for 108/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 3.5 kg |
| Part A: TEZ/IVA | Part A: Absolute Change in Body Weight for 108/110 Efficacy Set | IVA-TEZ/IVA: Change at Week 96 | 3.5 kg |
| Part A: TEZ/IVA | Part A: Absolute Change in Body Weight for 108/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | 3.6 kg |
Secondary
Part A: Absolute Change in Body Weight for 111/110 Efficacy Set
Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 111 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 111 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 111/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 111 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in Body Weight for 111/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 4.2 kg | Standard Deviation 5.7 |
| Part A: TEZ/IVA | Part A: Absolute Change in Body Weight for 111/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | 0.6 kg | Standard Deviation 2.6 |
Secondary
Part A: Absolute Change in Body Weight for Study 106/110 Efficacy Set
Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 106/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 106 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in Body Weight for Study 106/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 2.0 kg |
| Part A: TEZ/IVA | Part A: Absolute Change in Body Weight for Study 106/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | 2.1 kg |
Secondary
Part A: Absolute Change in Body Weight Z-score for 106/110 Efficacy Set
The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 106/110 efficacy set included all enrolled participants \<20 years of age at Screening who received at least 1 dose of study drug in Part A and rolled over from parent study 106 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in Body Weight Z-score for 106/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 0.07 z-score |
| Part A: TEZ/IVA | Part A: Absolute Change in Body Weight Z-score for 106/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | -0.06 z-score |
Secondary
Part A: Absolute Change in Body Weight Z-score for 108/110 Efficacy Set
The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 108/110 efficacy set included all enrolled participants \<20 years of age at Screening who received at least 1 dose of study drug in Part A and rolled over from parent study 108 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in Body Weight Z-score for 108/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 0.15 z-score |
| Part A: TEZ/IVA | Part A: Absolute Change in Body Weight Z-score for 108/110 Efficacy Set | IVA-TEZ/IVA: Change at Week 96 | 0.09 z-score |
| Part A: TEZ/IVA | Part A: Absolute Change in Body Weight Z-score for 108/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | 0.43 z-score |
Secondary
Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/110 Efficacy Set
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 103/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 103 and had pre-defined CFTR genotypes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/110 Efficacy Set | 8.6 units on a scale | Standard Deviation 12.1 |
Secondary
Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 106/110 Efficacy Set
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 106/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 106 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 106/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 1.7 units on a scale |
| Part A: TEZ/IVA | Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 106/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | 3.0 units on a scale |
Secondary
Part A: Absolute Change in Height Z-score for 106/110 Efficacy Set
The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 106/110 efficacy set included all enrolled participants \<20 years of age at Screening who received at least 1 dose of study drug in Part A and rolled over from parent study 106 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in Height Z-score for 106/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 0.01 z-score |
| Part A: TEZ/IVA | Part A: Absolute Change in Height Z-score for 106/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | 0.13 z-score |
Secondary
Part A: Absolute Change in Height Z-score for 108/110 Efficacy Set
The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 108/110 efficacy set included all enrolled participants \<20 years of age at Screening who received at least 1 dose of study drug in Part A and rolled over from parent study 108 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in Height Z-score for 108/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | 0.23 z-score |
| Part A: TEZ/IVA | Part A: Absolute Change in Height Z-score for 108/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | -0.04 z-score |
| Part A: TEZ/IVA | Part A: Absolute Change in Height Z-score for 108/110 Efficacy Set | IVA-TEZ/IVA: Change at Week 96 | 0.20 z-score |
Secondary
Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 103/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 103 and had pre-defined CFTR genotypes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set | 2.7 percentage points | Standard Deviation 10 |
Secondary
Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 106/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 106 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 2.1 percentage points |
| Part A: TEZ/IVA | Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | 2.0 percentage points |
Secondary
Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 108/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 108 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 4.1 percentage points |
| Part A: TEZ/IVA | Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set | IVA-TEZ/IVA: Change at Week 96 | 6.7 percentage points |
| Part A: TEZ/IVA | Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | 7.5 percentage points |
Secondary
Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 111 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 111 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 111/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 111 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: TEZ/IVA | Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 4.1 percentage points | Standard Deviation 10.2 |
| Part A: TEZ/IVA | Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | 2.6 percentage points | Standard Deviation 6.6 |
Secondary
Part A: Number of Pulmonary Exacerbation (PEx) Events for 106/110 PEx Analysis Set
Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
Time frame: From Baseline up to Study 110 Week 96
Population: The 106/110 PEx analysis set included study 106 participants who received TEZ/IVA in Study 106 or Study 110.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Number of Pulmonary Exacerbation (PEx) Events for 106/110 PEx Analysis Set | Placebo-TEZ/IVA | 306 PEx events |
| Part A: TEZ/IVA | Part A: Number of Pulmonary Exacerbation (PEx) Events for 106/110 PEx Analysis Set | TEZ/IVA-TEZ/IVA | 423 PEx events |
Secondary
Part A: Number of Pulmonary Exacerbation (PEx) Events for 108/110 PEx Analysis Set
Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline up to Week 96
Population: The 108/110 PEx analysis set included study 108 participants who received TEZ/IVA in Study 108 or Study 110.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Number of Pulmonary Exacerbation (PEx) Events for 108/110 PEx Analysis Set | Placebo-TEZ/IVA | 89 PEx events |
| Part A: TEZ/IVA | Part A: Number of Pulmonary Exacerbation (PEx) Events for 108/110 PEx Analysis Set | IVA-TEZ/IVA | 51 PEx events |
| Part A: TEZ/IVA | Part A: Number of Pulmonary Exacerbation (PEx) Events for 108/110 PEx Analysis Set | TEZ/IVA-TEZ/IVA | 46 PEx events |
Secondary
Part A: Plasma Concentrations of TEZ, TEZ Metabolite (M1-TEZ), Ivacaftor (IVA) and Ivacaftor Metabolite (M1-IVA)
Time frame: Week 24
Population: The Pharmacokinetic set included data for all participants who received TEZ/IVA treatment and met PK data inclusion and exclusion criteria.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: TEZ/IVA | Part A: Plasma Concentrations of TEZ, TEZ Metabolite (M1-TEZ), Ivacaftor (IVA) and Ivacaftor Metabolite (M1-IVA) | VX-661 | 2070 nanogram/milliliter (ng/mL) | Standard Deviation 1390 |
| Part A: TEZ/IVA | Part A: Plasma Concentrations of TEZ, TEZ Metabolite (M1-TEZ), Ivacaftor (IVA) and Ivacaftor Metabolite (M1-IVA) | M1-661 | 4580 nanogram/milliliter (ng/mL) | Standard Deviation 2080 |
| Part A: TEZ/IVA | Part A: Plasma Concentrations of TEZ, TEZ Metabolite (M1-TEZ), Ivacaftor (IVA) and Ivacaftor Metabolite (M1-IVA) | IVA | 892 nanogram/milliliter (ng/mL) | Standard Deviation 700 |
| Part A: TEZ/IVA | Part A: Plasma Concentrations of TEZ, TEZ Metabolite (M1-TEZ), Ivacaftor (IVA) and Ivacaftor Metabolite (M1-IVA) | M1-IVA | 1740 nanogram/milliliter (ng/mL) | Standard Deviation 1070 |
Secondary
Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 103/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 103 and had pre-defined CFTR genotypes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set | 6.4 percent change | Standard Deviation 21.1 |
Secondary
Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 106/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 106 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 4.3 percent change |
| Part A: TEZ/IVA | Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | 4.2 percent change |
Secondary
Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 108/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 108 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 7.9 percent change |
| Part A: TEZ/IVA | Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set | IVA-TEZ/IVA: Change at Week 96 | 11.6 percent change |
| Part A: TEZ/IVA | Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | 13.0 percent change |
Secondary
Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 111 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 111 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time frame: From Baseline at Study 110 Week 96
Population: The 111/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 111 and had pre-defined CFTR genotypes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: TEZ/IVA | Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set | Placebo-TEZ/IVA: Change at Week 96 | 6.1 percent change | Standard Deviation 14.4 |
| Part A: TEZ/IVA | Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set | TEZ/IVA-TEZ/IVA: Change at Week 96 | 5.2 percent change | Standard Deviation 11.5 |
Secondary
Part A: Time-to-first Pulmonary Exacerbation (PEx) for 106/110 PEx Analysis Set
Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan.
Time frame: 96 weeks
Population: The 106/110 PEx analysis set included study 106 participants who received TEZ/IVA in Study 106 or Study 110.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Time-to-first Pulmonary Exacerbation (PEx) for 106/110 PEx Analysis Set | Placebo-TEZ/IVA | 0.470 event-free probability |
| Part A: TEZ/IVA | Part A: Time-to-first Pulmonary Exacerbation (PEx) for 106/110 PEx Analysis Set | TEZ/IVA-TEZ/IVA | 0.438 event-free probability |
Secondary
Part A: Time-to-first Pulmonary Exacerbation (PEx) for 108/110 PEx Analysis Set
Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan.
Time frame: 96 weeks
Population: The 108/110 PEx analysis set included study 108 participants who received TEZ/IVA in Study 108 or Study 110.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: TEZ/IVA | Part A: Time-to-first Pulmonary Exacerbation (PEx) for 108/110 PEx Analysis Set | Placebo-TEZ/IVA | 0.497 event-free probability |
| Part A: TEZ/IVA | Part A: Time-to-first Pulmonary Exacerbation (PEx) for 108/110 PEx Analysis Set | IVA-TEZ/IVA | 0.493 event-free probability |
| Part A: TEZ/IVA | Part A: Time-to-first Pulmonary Exacerbation (PEx) for 108/110 PEx Analysis Set | TEZ/IVA-TEZ/IVA | 0.639 event-free probability |
Secondary
Part B: Absolute Change in BMI Z-score
The z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Time frame: From Baseline at Week 96
Population: The efficacy set included all enrolled participants who received at least 1 dose of study drug in Part B and rolled over from parent studies and had pre-defined CFTR genotypes. It was performed on each of the CFTR mutation groups separately (F508del/F508del and F508del/Residual Function).Here, Number Analyzed signifies participants who were evaluable for the specific category of CFTR genotypes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: TEZ/IVA | Part B: Absolute Change in BMI Z-score | F/F Mutation | -0.03 z-score | Standard Deviation 0.71 |
| Part A: TEZ/IVA | Part B: Absolute Change in BMI Z-score | F/RF Mutation | 0.21 z-score | Standard Deviation 0.46 |
Secondary
Part B: Absolute Change in Body Mass Index (BMI)
BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).
Time frame: From Baseline at Week 96
Population: The efficacy set included all enrolled participants who received at least 1 dose of study drug in Part B and rolled over from parent studies and had pre-defined CFTR genotypes. It was performed on each of the CFTR mutation groups separately (F508del/F508del and F508del/Residual Function). Here, Number Analyzed signifies participants who were evaluable for the specific category of CFTR genotypes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: TEZ/IVA | Part B: Absolute Change in Body Mass Index (BMI) | F/F Mutation | 0.70 kg/m^2 | Standard Deviation 1.45 |
| Part A: TEZ/IVA | Part B: Absolute Change in Body Mass Index (BMI) | F/RF Mutation | 1.84 kg/m^2 | Standard Deviation 2.21 |
Secondary
Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time frame: From Baseline at Study 110 Week 96
Population: The efficacy set included all enrolled participants who received at least 1 dose of study drug in Part B and rolled over from parent studies and had pre-defined CFTR genotypes. It was performed on each of the CFTR mutation groups separately (F508del/F508del and F508del/Residual Function). Here, Number Analyzed signifies participants who were evaluable for the specific category of CFTR genotypes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: TEZ/IVA | Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | F/F Mutation | 1.7 percentage points | Standard Deviation 10.2 |
| Part A: TEZ/IVA | Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | F/RF Mutation | 8.3 percentage points | Standard Deviation 8.6 |
Secondary
Part B: Number of Pulmonary Exacerbation (PEx) Events
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.
Time frame: From Baseline up to Week 96
Population: The efficacy set included all enrolled participants who received at least 1 dose of study drug in Part B and rolled over from parent studies and had pre-defined CFTR genotypes. It was performed on each of the CFTR mutation groups separately (F508del/F508del and F508del/Residual Function). Here, Number Analyzed signifies participants who were evaluable for the specific category of CFTR genotypes.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: TEZ/IVA | Part B: Number of Pulmonary Exacerbation (PEx) Events | F/F Mutation | 386 PEx events |
| Part A: TEZ/IVA | Part B: Number of Pulmonary Exacerbation (PEx) Events | F/RF Mutation | 94 PEx events |