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Evaluation of Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) in Cystic Fibrosis Subjects Without an F508del Mutation

A Phase 3 Double-blind, Randomized, Placebo-controlled Study Evaluating the Efficacy and Safety of ELX/TEZ/IVA in Cystic Fibrosis Subjects 6 Years of Age and Older With a Non-F508del ELX/TEZ/IVA-responsive CFTR Mutation

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT05274269
Enrollment
307
Registered
2022-03-10
Start date
2022-05-09
Completion date
2023-07-05
Last updated
2024-08-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cystic Fibrosis

Brief summary

This study evaluated the efficacy, pharmacodynamics (PD) and safety of ELX/TEZ/IVA in participants 6 years of age and older with a non-F508del ELX/TEZ/IVA-responsive cystic fibrosis transmembrane conductance regulator gene (CFTR) mutation.

Interventions

DRUGELX/TEZ/IVA

Fixed-dose combination (FDC) tablets for oral administration.

DRUGIVA

Tablet for oral administration.

OTHERPlacebo (matched to ELX/TEZ/IVA)

Placebo matched to ELX/TEZ/IVA for oral administration.

OTHERPlacebo (matched to IVA)

Placebo matched to IVA for oral administration.

Sponsors

Vertex Pharmaceuticals Incorporated
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No

Inclusion criteria

Key Inclusion Criteria: * Participant has a qualifying ELX/TEZ/IVA-responsive CFTR mutation and does not have an exclusionary CFTR mutation * Forced expiratory volume in 1 second (FEV1) value \>=40% and \<=100% of predicted mean for age, sex, and height Key

Exclusion criteria

* History of solid organ or hematological transplantation * Clinically significant cirrhosis with or without portal hypertension * Lung infection with organisms associated with a more rapid decline in pulmonary status Other protocol defined Inclusion/

Design outcomes

Primary

MeasureTime frameDescription
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)From Baseline Through Week 24FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Secondary

MeasureTime frameDescription
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain (RD) ScoreFrom Baseline Through Week 24The 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.
Absolute Change in Body Mass Index (BMI)From Baseline at Week 24BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).
Absolute Change in Sweat Chloride (SwCl)From Baseline Through Week 24Sweat samples were collected using an approved collection device.
Number of Pulmonary Exacerbations (PEx)From Baseline Through Week 24Pulmonary 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.
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)Day 1 up to Week 28—
Absolute Change in WeightFrom Baseline at Week 24—

Countries

Austria, Belgium, Canada, Czechia, France, Germany, Hungary, Italy, Netherlands, Norway, Poland, Portugal, Spain, Sweden, Switzerland

Participant flow

Recruitment details

This study was conducted in cystic fibrosis (CF) participants aged 6 years and older with a non-F508del ELX/TEZ/IVA-responsive cystic fibrosis transmembrane conductance regulator gene (CFTR) mutation.

Participants by arm

ArmCount
Placebo
Participants received placebo matched to ELX/TEZ/IVA FDC in the morning and placebo matched to IVA in the evening for 24 weeks.
102
ELX/TEZ/IVA
Participants 6 to \<12 years of age and weighing \<30kg 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 24 weeks. 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 24 weeks.
205
Total307

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyAdverse Event03
Overall StudyDeath01
Overall StudyOther02
Overall StudyWithdrawal of consent (not due to AE)02

Baseline characteristics

CharacteristicPlaceboELX/TEZ/IVATotal
Age, Continuous33.9 years
STANDARD_DEVIATION 16.4
33.3 years
STANDARD_DEVIATION 15.9
33.5 years
STANDARD_DEVIATION 16
Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)68.1 percent predicted FEV1
STANDARD_DEVIATION 18.1
67.5 percent predicted FEV1
STANDARD_DEVIATION 17.6
67.7 percent predicted FEV1
STANDARD_DEVIATION 17.7
Race/Ethnicity, Customized
Asian
2 Participants4 Participants6 Participants
Race/Ethnicity, Customized
Hispanic or Latino
3 Participants8 Participants11 Participants
Race/Ethnicity, Customized
Not Collected per Local Regulations
12 Participants26 Participants38 Participants
Race/Ethnicity, Customized
Not Hispanic or Latino
88 Participants171 Participants259 Participants
Race/Ethnicity, Customized
Other
1 Participants3 Participants4 Participants
Race/Ethnicity, Customized
White
86 Participants172 Participants258 Participants
Race/Ethnicity, Customized
White, Asian
1 Participants0 Participants1 Participants
Sex: Female, Male
Female
52 Participants113 Participants165 Participants
Sex: Female, Male
Male
50 Participants92 Participants142 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 1021 / 205
other
Total, other adverse events
86 / 102164 / 205
serious
Total, serious adverse events
15 / 10218 / 205

Outcome results

Primary

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 Through Week 24

Population: The Full Analysis Set (FAS) will include all randomized participants who carry the intended mutation and received at least 1 dose of study drug. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome measure.

ArmMeasureValue (LEAST_SQUARES_MEAN)
PlaceboAbsolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)-0.4 percent predicted FEV1
ELX/TEZ/IVAAbsolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)8.9 percent predicted FEV1
p-value: <0.000195% CI: [7.2, 11.3]Mixed Models for Repeated Measures
Secondary

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 24

Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome measure.

ArmMeasureValue (LEAST_SQUARES_MEAN)
PlaceboAbsolute Change in Body Mass Index (BMI)0.35 kg/m^2
ELX/TEZ/IVAAbsolute Change in Body Mass Index (BMI)0.81 kg/m^2
p-value: <0.000195% CI: [0.24, 0.69]Mixed Models for Repeated Measures
Secondary

Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain (RD) 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: From Baseline Through Week 24

Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome measure.

ArmMeasureValue (LEAST_SQUARES_MEAN)
PlaceboAbsolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain (RD) Score-2.0 units on a scale
ELX/TEZ/IVAAbsolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain (RD) Score17.5 units on a scale
p-value: <0.000195% CI: [15.5, 23.5]Mixed Models for 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 outcome measure.

ArmMeasureValue (LEAST_SQUARES_MEAN)
PlaceboAbsolute Change in Sweat Chloride (SwCl)0.5 millimole per liter (mmol/L)
ELX/TEZ/IVAAbsolute Change in Sweat Chloride (SwCl)-27.8 millimole per liter (mmol/L)
p-value: <0.000195% CI: [-32.1, -24.5]Mixed Models for Repeated Measures
Secondary

Absolute Change in Weight

Time frame: From Baseline at Week 24

Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome measure.

ArmMeasureValue (LEAST_SQUARES_MEAN)
PlaceboAbsolute Change in Weight1.2 kilogram (kg)
ELX/TEZ/IVAAbsolute Change in Weight2.4 kilogram (kg)
p-value: <0.000195% CI: [0.6, 1.9]Mixed Models for Repeated Measures
Secondary

Number of Pulmonary Exacerbations (PEx)

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 Through Week 24

Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this outcome measure.

ArmMeasureValue (NUMBER)
PlaceboNumber of Pulmonary Exacerbations (PEx)40 PEx events
ELX/TEZ/IVANumber of Pulmonary Exacerbations (PEx)21 PEx events
Secondary

Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame: Day 1 up to Week 28

Population: Safety Set was defined as all participants who received at least 1 dose of study drug.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
PlaceboSafety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)Participants with TEAEs97 Participants
PlaceboSafety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)Participants with SAEs15 Participants
ELX/TEZ/IVASafety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)Participants with TEAEs193 Participants
ELX/TEZ/IVASafety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)Participants with SAEs18 Participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026