Cystic Fibrosis
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF participants who are homozygous for F508del, heterozygous for F508del and a gating (F/G) or residual function (F/RF) mutation, or have at least 1 other TCR CF transmembrane conductance regulator (CFTR) gene mutation and no F508del mutation.
Interventions
DRUGVX-121/TEZ/D-IVA
Fixed-dose combination tablets for oral administration.
DRUGELX/TEZ/IVA
Fixed-dose combination tablets for oral administration.
DRUGIVA
Tablet for oral administration.
Placebo matched to VX-121/TEZ/D-IVA for oral administration.
Placebo matched to ELX/TEZ/IVA for oral administration.
Placebo matched to IVA for oral administration.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participant has one of the following genotypes: * Homozygous for F508del; * Heterozygous for F508del and a gating (F/G) mutation; * Heterozygous for F508del and a residual function (F/RF) mutation; * At least 1 other TCR CFTR gene mutation identified as responsive to ELX/TEZ/IVA and no F508del mutation * Forced expiratory volume in 1 second (FEV1) value \>=40% and \<=90% of predicted mean for age, sex, and height for participants currently receiving CFTR protein modulator therapy; FEV1 \>=40% and \<=80% for participants not currently receiving CFTR protein modulator therapy Key
Exclusion criteria
* History of solid organ or hematological transplantation * Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15) * Lung infection with organisms associated with a more rapid decline in pulmonary status * Pregnant or breast-feeding females Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in Percent Predicted Forced Expiratory Volume in 1second (ppFEV1) | From Baseline Through Week 24 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in Sweat Chloride (SwCl) | From Baseline Through Week 24 | Sweat samples were collected using an approved collection device. |
| Percentage of Participants With SwCl <60 Millimole Per Liter (mmol/L) (Pooled With Data From Study VX20-121-102) | From Baseline Through Week 24 | Sweat samples were collected using an approved collection device. |
| Percentage of Participants With SwCl <30 mmol/L (Pooled With Data From Study VX20-121-102) | From Baseline Through Week 24 | Sweat samples were collected using an approved collection device. |
Countries
Australia, Austria, Belgium, Canada, Denmark, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Netherlands, New Zealand, Norway, Poland, Sweden, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted in cystic fibrosis (CF) participants aged 12 years or older. It was pre-specified in the protocol to combine the data from this study with study VX20-121-102 (NCT05033080) for selected outcome measures.
Pre-assignment details
A total of 597 participants were enrolled in this study, of which 24 were included in the run-in period but were not dosed in treatment period. Therefore, results are presented for only 573 participants dosed in the treatment period.
Participants by arm
| Arm | Count |
|---|---|
| ELX/TEZ/IVA Following ELX/TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 52 weeks. | 289 |
| VX-121/TEZ/D-IVA Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks. | 284 |
| Total | 573 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 9 |
| Overall Study | Commercial drug is available for participant | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other | 5 | 4 |
| Overall Study | Other non compliance | 1 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal of consent (not due to AE) | 1 | 3 |
Baseline characteristics
| Characteristic | ELX/TEZ/IVA | VX-121/TEZ/D-IVA | Total |
|---|---|---|---|
| Age, Continuous | 34.0 years STANDARD_DEVIATION 12.4 | 33.3 years STANDARD_DEVIATION 12.6 | 33.7 years STANDARD_DEVIATION 12.5 |
| Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 66.4 Percentage points STANDARD_DEVIATION 14.9 | 67.2 Percentage points STANDARD_DEVIATION 14.6 | 66.8 Percentage points STANDARD_DEVIATION 14.7 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 5 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized More than one race | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Not Collected per Local Regulations | 23 Participants | 10 Participants | 38 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 261 Participants | 265 Participants | 526 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 262 Participants | 270 Participants | 532 Participants |
| Sex: Female, Male Female | 145 Participants | 135 Participants | 280 Participants |
| Sex: Female, Male Male | 144 Participants | 149 Participants | 293 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 289 | 0 / 284 |
| other Total, other adverse events | 253 / 289 | 252 / 284 |
| serious Total, serious adverse events | 40 / 289 | 40 / 284 |
Outcome results
Primary
Absolute Change in Percent Predicted Forced Expiratory Volume in 1second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time frame: From Baseline Through Week 24
Population: The Full Analysis Set (FAS) included all randomized participants who carried the intended CFTR mutation(s) and received at least 1 dose of study drug during the Treatment Period. Here Overall Number of participants Analyzed signifies those participants who were evaluated for this specific outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| ELX/TEZ/IVA | Absolute Change in Percent Predicted Forced Expiratory Volume in 1second (ppFEV1) | 0.0 percentage points |
| VX-121/TEZ/D-IVA | Absolute Change in Percent Predicted Forced Expiratory Volume in 1second (ppFEV1) | 0.2 percentage points |
p-value: <0.000195% CI: [-0.5, 0.9]Mixed Models Repeated Measures
Secondary
Absolute Change in Sweat Chloride (SwCl)
Sweat samples were collected using an approved collection device.
Time frame: From Baseline Through Week 24
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this specific outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| ELX/TEZ/IVA | Absolute Change in Sweat Chloride (SwCl) | -2.3 millimole per liter (mmol/L) |
| VX-121/TEZ/D-IVA | Absolute Change in Sweat Chloride (SwCl) | -5.1 millimole per liter (mmol/L) |
p-value: =0.003495% CI: [-4.7, -0.9]Mixed Models Repeated Measures
Secondary
Percentage of Participants With SwCl <30 mmol/L (Pooled With Data From Study VX20-121-102)
Sweat samples were collected using an approved collection device.
Time frame: From Baseline Through Week 24
Population: PFAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this specific outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ELX/TEZ/IVA | Percentage of Participants With SwCl <30 mmol/L (Pooled With Data From Study VX20-121-102) | 22.5 percentage of participants |
| VX-121/TEZ/D-IVA | Percentage of Participants With SwCl <30 mmol/L (Pooled With Data From Study VX20-121-102) | 30.5 percentage of participants |
p-value: <0.000195% CI: [2, 4.12]Generalized Estimated Equation Model
Secondary
Percentage of Participants With SwCl <60 Millimole Per Liter (mmol/L) (Pooled With Data From Study VX20-121-102)
Sweat samples were collected using an approved collection device.
Time frame: From Baseline Through Week 24
Population: The Pooled Full Analysis Set (PFAS) included all randomized participants from this study (VX20-121-102) and from Study VX20-121-103 who carried the intended CFTR mutation(s) and received at least 1 dose of study drug during the Treatment Period. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this specific outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ELX/TEZ/IVA | Percentage of Participants With SwCl <60 Millimole Per Liter (mmol/L) (Pooled With Data From Study VX20-121-102) | 76.6 percentage of participants |
| VX-121/TEZ/D-IVA | Percentage of Participants With SwCl <60 Millimole Per Liter (mmol/L) (Pooled With Data From Study VX20-121-102) | 85.8 percentage of participants |
p-value: <0.000195% CI: [1.55, 3.16]Generalized Estimated Equation Model