Cystic Fibrosis
Conditions
Brief summary
The study evaluates the long-term safety and efficacy of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) triple combination (TC) in participants with CF who are 6 years of age and older with F/MF genotypes.
Interventions
DRUGELX/TEZ/IVA
Fixed dose combination (FDC) tablets 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
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Completed study drug treatment in parent study (VX19-445-116, NCT04353817), or had study drug interruption(s) in parent study but completed study visits up to the last scheduled visit of the treatment period in the parent study Key
Exclusion criteria
* History of study drug intolerance in the parent study Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From Baseline up to Week 100 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Parent Study Baseline in Sweat Chloride (SwCl) | From Parent Study Baseline to Week 96 | Sweat samples were collected using an approved collection device. |
| Absolute Change From Parent Study Baseline in Lung Clearance Index 2.5 (LCI2.5) | From Parent Study Baseline to Week 96 | The LCI2.5 index is the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting values and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured functional residual capacity (FRC). An LCI of 7.5 and below is normal; values greater than 7.5 are abnormal. LCI is able to detect abnormalities in lung function earlier than more traditional modalities such as spirometry. |
Countries
Australia, Canada, Denmark, France, Germany, Israel, Netherlands, Spain, Switzerland, United Kingdom
Participant flow
Pre-assignment details
A total of 120 participants from the parent study VX19-445-116 (NCT04353817) were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| ELX/TEZ/IVA Participants 6 to \<12 year of age and weighing \<30 kg at Day 1 received ELX 100 mg/TEZ 50 mg /IVA 75 mg as FDC tablets in the morning and IVA as mono tablet in the evening and those weighing ≥30 kg at Day 1 received ELX 200 mg/TEZ 100 mg /IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 96 weeks. Doses were adjusted upward with subsequent changes in weight. Participants ≥12 years age at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 96 weeks. | 120 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Commercial drug is available for participant | 7 |
| Overall Study | Withdrawal of consent (not due to AE) | 2 |
Baseline characteristics
| Characteristic | ELX/TEZ/IVA |
|---|---|
| Age, Continuous | 9.1 years STANDARD_DEVIATION 1.7 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants |
| Race/Ethnicity, Customized Multiracial | 1 Participants |
| Race/Ethnicity, Customized Not collected per local regulations | 29 Participants |
| Race/Ethnicity, Customized Not collected per local Regulations | 28 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 90 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 87 Participants |
| Sex: Female, Male Female | 69 Participants |
| Sex: Female, Male Male | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 120 |
| other Total, other adverse events | 118 / 120 |
| serious Total, serious adverse events | 13 / 120 |
Outcome results
Primary
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From Baseline up to Week 100
Population: The Open-label Safety Set (OL-SS) included all participants who had received at least 1 dose of study drug in the Open label extension (OLE) study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ELX/TEZ/IVA | Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 118 Participants |
| ELX/TEZ/IVA | Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 13 Participants |
Secondary
Absolute Change From Parent Study Baseline in Lung Clearance Index 2.5 (LCI2.5)
The LCI2.5 index is the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting values and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured functional residual capacity (FRC). An LCI of 7.5 and below is normal; values greater than 7.5 are abnormal. LCI is able to detect abnormalities in lung function earlier than more traditional modalities such as spirometry.
Time frame: From Parent Study Baseline to Week 96
Population: OL-FAS. Data were planned to be presented as per parent study reporting groups (i.e. Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA). Here Overall number of participants analyzed signifies participants who were evaluable for this outcome at Week 96 and Number Analyzed signifies participants who were evaluable in the specified parent study reporting group.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ELX/TEZ/IVA | Absolute Change From Parent Study Baseline in Lung Clearance Index 2.5 (LCI2.5) | Placebo (Parent study)-ELX/TEZ/IVA (Current study) | -1.74 Index | Standard Error 0.18 |
| ELX/TEZ/IVA | Absolute Change From Parent Study Baseline in Lung Clearance Index 2.5 (LCI2.5) | ELX/TEZ/IVA (Parent study)-ELX/TEZ/IVA (Current study) | -2.35 Index | Standard Error 0.19 |
Secondary
Absolute Change From Parent Study Baseline in Sweat Chloride (SwCl)
Sweat samples were collected using an approved collection device.
Time frame: From Parent Study Baseline to Week 96
Population: OL Full Analysis Set (OL-FAS) included all enrolled participants who received at least 1 dose of study drug in this study. Data were planned to be presented as per parent study reporting groups (i.e. Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA). Here Overall number of participants analyzed signifies participants who were evaluable for this outcome at Week 96 and Number Analyzed signifies participants who were evaluable in the specified parent study reporting group.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ELX/TEZ/IVA | Absolute Change From Parent Study Baseline in Sweat Chloride (SwCl) | Placebo (Parent study)-ELX/TEZ/IVA (Current study) | -57.3 millimole per liter (mmol/L) | Standard Error 2.2 |
| ELX/TEZ/IVA | Absolute Change From Parent Study Baseline in Sweat Chloride (SwCl) | ELX/TEZ/IVA (Parent study)-ELX/TEZ/IVA (Current study) | -57.5 millimole per liter (mmol/L) | Standard Error 2.3 |