Evaluation of Long-term Safety and Efficacy of ELX/TEZ/IVA TC Combination Therapy in Participants With Cystic Fibrosis Who Are 6 Years of Age and Older

Conditions

Cystic Fibrosis

Brief summary

The study evaluates the long-term safety, tolerability, efficacy, and pharmacodynamics of elexacaftor (ELX, VX-445) in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in participants with cystic fibrosis (CF).

Wainwright C, McColley SA, McNally P, Powers M, Ratjen F, Rayment JH, Retsch-Bogart G, Roesch E, Ramsey B, McKone EF, Tullis E, Mall MA, Taylor-Cousar JL, Waltz D, Ahluwalia N, Chu C, Scirica CV, Davies JC.

2025-10-012 citations

10.1164/rccm.202502-0512oc

Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged ≥6 Years with Cystic Fibrosis and at Least One <i>F508del</i> Allele: A Phase 3, Open-Label Clinical Trial

Claire Wainwright, Susanna A. McColley, Paul McNally, Michael R. Powers, Félix Ratjen et al. (17 authors)

American Journal of Respiratory and Critical Care Medicine2023-05-0857 citations

10.1164/rccm.202301-0021oc

A Phase 3 Open-Label Study of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 through 11 Years of Age with Cystic Fibrosis and at Least One <i>F508del</i> Allele

Edith T. Zemanick, Jennifer L. Taylor‐Cousar, Jane C. Davies, Ronald L. Gibson, Marcus Mall et al. (22 authors)

American Journal of Respiratory and Critical Care Medicine2021-03-18259 citations

10.1164/rccm.202102-0509oc

Interventions

DRUGELX/TEZ/IVA

Fixed-dose combination (FDC) tablet for oral administration

DRUGIVA

Mono tablet for oral administration.

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 (VX18-445-106 Part B, NCT03691779), 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 parent study Other protocol defined Inclusion/

Design outcomes

Primary

Measure	Time frame
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	From Baseline up to Week 196

Secondary

Measure	Time frame	Description
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	From Baseline up to Week 192	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change in Sweat Chloride (SwCl)	From Baseline up to Week 192	Sweat samples were collected using an approved collection device.
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score	From Baseline up to Week 192	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.
Absolute Change in Body Mass Index (BMI)	From Baseline up to Week 192	BMI was defined as weight in kg divided by squared height in meters (m\^2).
Absolute Change in BMI-for-age Z-score	From Baseline up to Week 192	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 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.
Number of CF-related Hospitalizations for 106/107	From Baseline up to Week 192	The total number of CF related hospitalization (Planned + Unplanned) events across all participants were reported.
Absolute Change in Lung Clearance Index 2.5 (LCI 2.5)	From Baseline up to Week 192	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.
Absolute Change in Weight	From Baseline up to Week 192	—
Absolute Change in Weight-for-age Z-score	From Baseline up to Week 192	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.
Absolute Change in Height	From Baseline up to Week 192	—
Absolute Change in Height-for-age Z-score	From Baseline up to Week 192	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.
Number of Participants With Pulmonary Exacerbations (PEx) for 106/107	From Baseline up to Week 192	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.

Countries

Australia, Canada, Ireland, United Kingdom, United States

Participant flow

Recruitment details

The study was conducted in two parts, Part A and Part B. Participants of both Parts A and B received the same treatment (ELX,TEZ,IVA). Therefore, results data were planned to be collected and analyzed for the overall population of the study and not for separate parts.

Pre-assignment details

Participants from parent study VX18-445-106 Part B (NCT03691779) were enrolled in this study. A total of 64 participants were enrolled in this open label extension study.

Participants by arm

Arm	Count
ELX/TEZ/IVA Participants ≥6 years and \<12 years of age and weighing \<30 kg received ELX 100 mg qd /TEZ 50 mg qd/IVA 75 mg q12h and those weighing ≥30 kg received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg in the treatment period for up to192 weeks. Participants ≥12 years of age received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for up to 192 weeks.	64
Total	64

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	0
Overall Study	Commercial drug is available for participant	6	0
Overall Study	Not enrolled in 107 study	0	2
Overall Study	Participants did not rollover to Part B	12	0
Overall Study	Withdrawal of consent (not due to AE)	6	0

Baseline characteristics

Characteristic	ELX/TEZ/IVA
Age, Continuous	9.3 years STANDARD_DEVIATION 1.8
Race/Ethnicity, Customized Asian	0 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 Participants
Race/Ethnicity, Customized More than one Race	1 Participants
Race/Ethnicity, Customized Not collected per local regulations	8 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	56 Participants
Race/Ethnicity, Customized White	55 Participants
Sex: Female, Male Female	39 Participants
Sex: Female, Male Male	25 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 64
other Total, other adverse events	62 / 64
serious Total, serious adverse events	7 / 64

Outcome results

Primary

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

Time frame: From Baseline up to Week 196

Population: OLE Safety Set was defined as all subjects who received at least 1 dose of study drug in this OLE study. Data for this outcome measure was planned to be collected and analyzed for the overall ELX/TEZ/IVA arm irrespective of Part A and B separately.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
ELX/TEZ/IVA	Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Participants with TEAEs	64 Participants
ELX/TEZ/IVA	Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Participants with SAEs	7 Participants

Secondary

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 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.