Cystic Fibrosis
Conditions
Brief summary
This study will evaluate the pharmacokinetics (PK), safety, tolerability, efficacy, and pharmacodynamic effect of VX-445, tezacaftor (TEZ), and ivacaftor (IVA) when dosed in triple combination (TC) in Cystic Fibrosis (CF) subjects 6 through 11 years of age with F/F and F/MF genotypes.
Interventions
DRUGELX/TEZ/IVA
Fixed-dose combination tablet orally once daily in the morning.
DRUGIVA
IVA tablet orally once daily in the evening.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Homozygous or heterozygous for F508del mutation (F/F or F/MF genotypes) * Forced expiratory volume in 1 second (FEV1) value ≥40% of predicted mean for age, sex, and height. Key
Exclusion criteria
* Clinically significant cirrhosis with or without portal hypertension * Lung infection with organisms associated with a more rapid decline in pulmonary status. * Solid organ or hematological transplantation. Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: Area Under the Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24h) of ELX, TEZ, and IVA | Part A: Day 15 |
| Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA | Part A: Day 15 |
| Part A: Observed Pre-dose Plasma Concentration (Ctrough) of ELX, TEZ, and IVA | Part A: Day 15 |
| Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Part B: Day 1 Through Safety Follow-up Visit (up to Week 28) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Safety and Tolerability as Assessed by Number of Participants With TEAEs and SAEs | Part A: Day 1 Through Safety Follow-up Visit (up to Day 43) | — |
| Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | Part B: From Baseline Through Week 24 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
| Part B: Absolute Change in Sweat Chloride (SwCl) | Part B: From Baseline Through Week 24 | Sweat samples were collected using an approved collection device. |
| Part B: Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score | Part B: From Baseline Through Week 24 | 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. |
| Part B: Absolute Change in Body Mass Index (BMI) | Part B: From Baseline at Week 24 | BMI was defined as weight in kg divided by squared height in meters (m\^2). |
| Part B: Absolute Change in BMI For-Age Z-Score | Part B: From Baseline at Week 24 | BMI was defined as weight in kg divided by squared height in meters (m\^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. |
| Part B: Absolute Change in Weight | Part B: From Baseline at Week 24 | — |
| Part A: Cmax of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) | Part A: Day 15 | — |
| Part B: Absolute Change in Height | Part B: From Baseline at Week 24 | — |
| Part B: Absolute Change in Height-for-Age Z-Score | Part B: From Baseline at Week 24 | The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. |
| Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale | Part B: At Week 24 | The study drug acceptability (participant reaction) was assessed by a visual analog scale that incorporates a 5 point facial hedonic scale (Liked it Very Much, Liked it a Little, Not sure, Disliked it a Little, Disliked it Very Much). Number of participants with the indicated categorical response in the drug acceptability assessment were reported. |
| Part B: Number of Pulmonary Exacerbations Events | Part B: From Baseline Through Week 24 | Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol defined criteria. The total number of pulmonary exacerbations events across all participants were reported. |
| Part B: Number of CF Related Hospitalizations | Part B: From Baseline Through Week 24 | The total number of CF related hospitalization events across all participants were reported. |
| Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) | Part B: At Week 4 | — |
| Part B: Absolute Change in Lung Clearance Index 2.5 (LCI2.5) | Part B: From Baseline Through Week 24 | LCI 2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value. |
| Part B: Absolute Change in Weight-for-age Z-Score | Part B: From Baseline at Week 24 | The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. |
| Part A: Ctrough of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) | Part A: Day 15 | — |
| Part A: AUC0-24h of ELX Metabolite (M23-ELX) and TEZ Metabolite (M1-TEZ) | Part A: Day 15 | — |
| Part A: Area Under the Concentration Versus Time Curve From 0 to 6 Hours (AUC0-6h) of IVA Metabolite (M1-IVA) | Part A: Day 15 | The AUC data was analyzed for up to 6 hours for IVA metabolite (M1-IVA). Therefore, AUC0-6h is reported for M1-IVA metabolite. |
Countries
Australia, Canada, Ireland, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted in 2 parts, Part A and Part B. All results were planned to be analyzed and reported separately for Part A and Part B of the study.
Pre-assignment details
This study was conducted in cystic fibrosis (CF) participants 6 through 11 years of age who were homozygous for F508del (F/F) genotype or heterozygous for F508del and a CF transmembrane conductance regulator gene (CFTR) minimal function mutation (F/MF) genotypes.
Participants by arm
| Arm | Count |
|---|---|
| ELX/TEZ/IVA Part A: Participants in Part A received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days.
Part B: Participants in Part B weighing \<30 kg at Day 1 received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing \>=30 kg at Day 1 received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks. | 71 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part B (24 Weeks) | Adverse Event | 0 | 1 |
| Part B (24 Weeks) | Withdrawal of consent (not due to AE) | 0 | 1 |
Baseline characteristics
| Characteristic | ELX/TEZ/IVA |
|---|---|
| Age, Categorical Part A (15 Days) <=18 years | 16 Participants |
| Age, Categorical Part A (15 Days) >=65 years | 0 Participants |
| Age, Categorical Part A (15 Days) Between 18 and 65 years | 0 Participants |
| Age, Categorical Part B (24 Weeks) <=18 years | 66 Participants |
| Age, Categorical Part B (24 Weeks) >=65 years | 0 Participants |
| Age, Categorical Part B (24 Weeks) Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Part A (15 Days) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Part A (15 Days) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Part A (15 Days) Unknown or Not Reported | 0 Participants |
| Ethnicity (NIH/OMB) Part B (24 Weeks) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Part B (24 Weeks) Not Hispanic or Latino | 58 Participants |
| Ethnicity (NIH/OMB) Part B (24 Weeks) Unknown or Not Reported | 8 Participants |
| Race (NIH/OMB) Part A (15 Days) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Part A (15 Days) Asian | 0 Participants |
| Race (NIH/OMB) Part A (15 Days) Black or African American | 0 Participants |
| Race (NIH/OMB) Part A (15 Days) More than one race | 0 Participants |
| Race (NIH/OMB) Part A (15 Days) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Part A (15 Days) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Part A (15 Days) White | 16 Participants |
| Race (NIH/OMB) Part B (24 Weeks) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Part B (24 Weeks) Asian | 0 Participants |
| Race (NIH/OMB) Part B (24 Weeks) Black or African American | 0 Participants |
| Race (NIH/OMB) Part B (24 Weeks) More than one race | 1 Participants |
| Race (NIH/OMB) Part B (24 Weeks) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Part B (24 Weeks) Unknown or Not Reported | 8 Participants |
| Race (NIH/OMB) Part B (24 Weeks) White | 57 Participants |
| Sex: Female, Male Part A (15 Days) Female | 11 Participants |
| Sex: Female, Male Part A (15 Days) Male | 5 Participants |
| Sex: Female, Male Part B (24 Weeks) Female | 39 Participants |
| Sex: Female, Male Part B (24 Weeks) Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 66 |
| other Total, other adverse events | 12 / 16 | 62 / 66 |
| serious Total, serious adverse events | 0 / 16 | 1 / 66 |
Outcome results
Primary
Part A: Area Under the Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24h) of ELX, TEZ, and IVA
Time frame: Part A: Day 15
Population: PK set (Part A). This outcome measure was planned only for Part A arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: ELX/TEZ/IVA | Part A: Area Under the Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24h) of ELX, TEZ, and IVA | ELX | 107 hour*microgram per milliliter (h*mcg/mL) | Standard Deviation 28.7 |
| Part A: ELX/TEZ/IVA | Part A: Area Under the Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24h) of ELX, TEZ, and IVA | TEZ | 58.4 hour*microgram per milliliter (h*mcg/mL) | Standard Deviation 13.5 |
| Part A: ELX/TEZ/IVA | Part A: Area Under the Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24h) of ELX, TEZ, and IVA | IVA | 8.12 hour*microgram per milliliter (h*mcg/mL) | Standard Deviation 2.93 |
Primary
Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA
Time frame: Part A: Day 15
Population: Pharmacokinetic (PK) set for Part A included all participants who have received at least 1 dose of study drug in Part A. Here, the number analyzed signifies participants who were evaluable at the specified time point. This outcome measure was planned only for Part A arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: ELX/TEZ/IVA | Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA | ELX | 6.13 microgram per milliliter (mcg/mL) | Standard Deviation 1.52 |
| Part A: ELX/TEZ/IVA | Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA | TEZ | 6.93 microgram per milliliter (mcg/mL) | Standard Deviation 1.96 |
| Part A: ELX/TEZ/IVA | Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA | IVA | 1.01 microgram per milliliter (mcg/mL) | Standard Deviation 0.281 |
Primary
Part A: Observed Pre-dose Plasma Concentration (Ctrough) of ELX, TEZ, and IVA
Time frame: Part A: Day 15
Population: PK set (Part A). Here, the number analyzed signifies participants who were evaluable at the specified time point. This outcome measure was planned only for Part A arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: ELX/TEZ/IVA | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of ELX, TEZ, and IVA | IVA | 0.297 mcg/mL | Standard Deviation 0.173 |
| Part A: ELX/TEZ/IVA | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of ELX, TEZ, and IVA | ELX | 2.86 mcg/mL | Standard Deviation 1.37 |
| Part A: ELX/TEZ/IVA | Part A: Observed Pre-dose Plasma Concentration (Ctrough) of ELX, TEZ, and IVA | TEZ | 1.06 mcg/mL | Standard Deviation 0.366 |
Primary
Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Part B: Day 1 Through Safety Follow-up Visit (up to Week 28)
Population: Safety set for Part B included all participants who received at least 1 dose of study drug in Part B. The safety and tolerability analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: ELX/TEZ/IVA | Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With TEAEs | 65 participants |
| Part A: ELX/TEZ/IVA | Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 1 participants |
Secondary
Part A: Area Under the Concentration Versus Time Curve From 0 to 6 Hours (AUC0-6h) of IVA Metabolite (M1-IVA)
The AUC data was analyzed for up to 6 hours for IVA metabolite (M1-IVA). Therefore, AUC0-6h is reported for M1-IVA metabolite.
Time frame: Part A: Day 15
Population: PK set (Part A). Here overall number of participants analyzed signifies participants who were evaluable at the specified time points. This outcome measure was planned only for Part A arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: ELX/TEZ/IVA | Part A: Area Under the Concentration Versus Time Curve From 0 to 6 Hours (AUC0-6h) of IVA Metabolite (M1-IVA) | 9.41 h*mcg/mL | Standard Deviation 3.06 |
Secondary
Part A: AUC0-24h of ELX Metabolite (M23-ELX) and TEZ Metabolite (M1-TEZ)
Time frame: Part A: Day 15
Population: PK set (Part A). This outcome measure was planned only for Part A arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: ELX/TEZ/IVA | Part A: AUC0-24h of ELX Metabolite (M23-ELX) and TEZ Metabolite (M1-TEZ) | M23-ELX | 35.6 h*mcg/mL | Standard Deviation 13.2 |
| Part A: ELX/TEZ/IVA | Part A: AUC0-24h of ELX Metabolite (M23-ELX) and TEZ Metabolite (M1-TEZ) | M1-TEZ | 133 h*mcg/mL | Standard Deviation 30.4 |
Secondary
Part A: Cmax of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)
Time frame: Part A: Day 15
Population: PK set (Part A). Here, the number analyzed signifies participants who were evaluable at the specified time point. This outcome measure was planned only for Part A arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: ELX/TEZ/IVA | Part A: Cmax of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) | M23-ELX | 1.60 mcg/mL | Standard Deviation 0.657 |
| Part A: ELX/TEZ/IVA | Part A: Cmax of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) | M1-TEZ | 6.26 mcg/mL | Standard Deviation 1.54 |
| Part A: ELX/TEZ/IVA | Part A: Cmax of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) | M1-IVA | 2.36 mcg/mL | Standard Deviation 0.694 |
Secondary
Part A: Ctrough of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)
Time frame: Part A: Day 15
Population: PK set (Part A). Here, the number analyzed signifies participants who were evaluable at the specified time point. This outcome measure was planned only for Part A arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: ELX/TEZ/IVA | Part A: Ctrough of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) | M23-ELX | 1.30 mcg/mL | Standard Deviation 0.585 |
| Part A: ELX/TEZ/IVA | Part A: Ctrough of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) | M1-TEZ | 4.64 mcg/mL | Standard Deviation 1.36 |
| Part A: ELX/TEZ/IVA | Part A: Ctrough of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) | M1-IVA | 0.890 mcg/mL | Standard Deviation 0.46 |
Secondary
Part A: Safety and Tolerability as Assessed by Number of Participants With TEAEs and SAEs
Time frame: Part A: Day 1 Through Safety Follow-up Visit (up to Day 43)
Population: Safety set for Part A included all participants who received at least 1 dose of study drug in Part A. This outcome measure was planned only for Part A arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: ELX/TEZ/IVA | Part A: Safety and Tolerability as Assessed by Number of Participants With TEAEs and SAEs | Participants With TEAEs | 12 participants |
| Part A: ELX/TEZ/IVA | Part A: Safety and Tolerability as Assessed by Number of Participants With TEAEs and SAEs | Participants With SAEs | 0 participants |
Secondary
Part B: Absolute Change in BMI For-Age Z-Score
BMI was defined as weight in kg divided by squared height in meters (m\^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
Time frame: Part B: From Baseline at Week 24
Population: FAS (Part B). The efficacy analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: ELX/TEZ/IVA | Part B: Absolute Change in BMI For-Age Z-Score | 0.37 z-score |
Secondary
Part B: Absolute Change in Body Mass Index (BMI)
BMI was defined as weight in kg divided by squared height in meters (m\^2).
Time frame: Part B: From Baseline at Week 24
Population: FAS (Part B). The efficacy analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: ELX/TEZ/IVA | Part B: Absolute Change in Body Mass Index (BMI) | 1.02 kg/m^2 |
Secondary
Part B: Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score
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.
Time frame: Part B: From Baseline Through Week 24
Population: FAS (Part B). The efficacy analysis for Part B was planned for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: ELX/TEZ/IVA | Part B: Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score | 7.0 units on a scale |
Secondary
Part B: Absolute Change in Height
Time frame: Part B: From Baseline at Week 24
Population: FAS (Part B). The efficacy analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: ELX/TEZ/IVA | Part B: Absolute Change in Height | 2.3 centimeters (cm) |
Secondary
Part B: Absolute Change in Height-for-Age Z-Score
The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
Time frame: Part B: From Baseline at Week 24
Population: FAS (Part B). The efficacy analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: ELX/TEZ/IVA | Part B: Absolute Change in Height-for-Age Z-Score | -0.05 z-score |
Secondary
Part B: Absolute Change in Lung Clearance Index 2.5 (LCI2.5)
LCI 2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Time frame: Part B: From Baseline Through Week 24
Population: FAS (Part B). The efficacy analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: ELX/TEZ/IVA | Part B: Absolute Change in Lung Clearance Index 2.5 (LCI2.5) | -1.71 lung clearance index |
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: Part B: From Baseline Through Week 24
Population: Full analysis set (FAS) for Part B included all enrolled participants who carry the intended CFTR allele mutation and received at least 1 dose of study drug in Part B. The efficacy analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: ELX/TEZ/IVA | Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 10.2 percentage points |
Secondary
Part B: Absolute Change in Sweat Chloride (SwCl)
Sweat samples were collected using an approved collection device.
Time frame: Part B: From Baseline Through Week 24
Population: FAS (Part B). The efficacy analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: ELX/TEZ/IVA | Part B: Absolute Change in Sweat Chloride (SwCl) | -60.9 millimole per liter (mmol/L) |
Secondary
Part B: Absolute Change in Weight
Time frame: Part B: From Baseline at Week 24
Population: FAS (Part B). The efficacy analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: ELX/TEZ/IVA | Part B: Absolute Change in Weight | 3.0 kg |
Secondary
Part B: Absolute Change in Weight-for-age Z-Score
The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
Time frame: Part B: From Baseline at Week 24
Population: FAS (Part B). The efficacy analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: ELX/TEZ/IVA | Part B: Absolute Change in Weight-for-age Z-Score | 0.25 z-score |
Secondary
Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA)
Time frame: Part B: At Week 4
Population: The PK set for Part B included all participants who have received at least 1 dose of study drug in Part B. Here number analyzed signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: ELX/TEZ/IVA | Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) | ELX: Week 4 (<30 kg) | 2.71 mcg/mL | Standard Deviation 1.77 |
| Part A: ELX/TEZ/IVA | Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) | ELX: Week 4 (>=30 kg) | 5.69 mcg/mL | Standard Deviation 3 |
| Part A: ELX/TEZ/IVA | Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) | M23-ELX: Week 4 (<30 kg) | 1.59 mcg/mL | Standard Deviation 1.24 |
| Part A: ELX/TEZ/IVA | Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) | M23-ELX: Week 4 (>=30 kg) | 4.41 mcg/mL | Standard Deviation 2.97 |
| Part A: ELX/TEZ/IVA | Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) | TEZ: Week 4 (<30 kg) | 1.43 mcg/mL | Standard Deviation 1.19 |
| Part A: ELX/TEZ/IVA | Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) | TEZ: Week 4 (>=30 kg) | 2.37 mcg/mL | Standard Deviation 1.07 |
| Part A: ELX/TEZ/IVA | Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) | M1-TEZ: Week 4 (<30 kg) | 5.57 mcg/mL | Standard Deviation 1.78 |
| Part A: ELX/TEZ/IVA | Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) | M1-TEZ: Week 4 (>=30 kg) | 8.12 mcg/mL | Standard Deviation 1.88 |
| Part A: ELX/TEZ/IVA | Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) | IVA: Week 4 (<30 kg) | 0.455 mcg/mL | Standard Deviation 0.681 |
| Part A: ELX/TEZ/IVA | Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) | IVA: Week 4 (>=30 kg) | 0.851 mcg/mL | Standard Deviation 0.489 |
| Part A: ELX/TEZ/IVA | Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) | M1-IVA: Week 4 (<30 kg) | 1.00 mcg/mL | Standard Deviation 0.63 |
| Part A: ELX/TEZ/IVA | Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA) | M1-IVA: Week 4 (>=30 kg) | 2.18 mcg/mL | Standard Deviation 1.04 |
Secondary
Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale
The study drug acceptability (participant reaction) was assessed by a visual analog scale that incorporates a 5 point facial hedonic scale (Liked it Very Much, Liked it a Little, Not sure, Disliked it a Little, Disliked it Very Much). Number of participants with the indicated categorical response in the drug acceptability assessment were reported.
Time frame: Part B: At Week 24
Population: FAS (Part B). The efficacy analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm. Here Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: ELX/TEZ/IVA | Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale | Disliked it a Little | 1 participants |
| Part A: ELX/TEZ/IVA | Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale | Liked it Very Much | 16 participants |
| Part A: ELX/TEZ/IVA | Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale | Liked it a Little | 6 participants |
| Part A: ELX/TEZ/IVA | Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale | Not sure | 10 participants |
| Part A: ELX/TEZ/IVA | Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale | Disliked it Very Much | 0 participants |
Secondary
Part B: Number of CF Related Hospitalizations
The total number of CF related hospitalization events across all participants were reported.
Time frame: Part B: From Baseline Through Week 24
Population: FAS (Part B). The efficacy analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: ELX/TEZ/IVA | Part B: Number of CF Related Hospitalizations | 0 hospitalizations |
Secondary
Part B: Number of Pulmonary Exacerbations Events
Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol defined criteria. The total number of pulmonary exacerbations events across all participants were reported.
Time frame: Part B: From Baseline Through Week 24
Population: FAS (Part B). The efficacy analysis for Part B was assessed for the overall treatment arm, irrespective of weight based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: ELX/TEZ/IVA | Part B: Number of Pulmonary Exacerbations Events | 4 pulmonary exacerbations events |