Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy

A Phase 3, Open-label Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04058366

Enrollment

251

Registered

2019-08-15

Start date

2019-12-05

Completion date

2022-12-16

Last updated

2024-01-16

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 long-term safety, efficacy, and pharmacodynamics of elexacaftor (ELX, VX-445) in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for the F508del mutation and a gating or residual function mutation (F/G and F/RF genotypes).

Interventions

DRUGELX/TEZ/IVA

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

DRUGIVA

Tablet for oral administration.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

12 Years to No maximum

Healthy volunteers

Inclusion criteria

Key Inclusion Criteria: * Completed study drug treatment in parent study (VX18-445-104); 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
Part A: 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 100

Secondary

Measure	Time frame	Description
Part A: Absolute Change From Parent Study Baseline in Sweat Chloride (SwCl)	From Baseline at Week 96	Sweat samples were collected using an approved collection device.
Part A: Absolute Change From Parent Study Baseline in Body Mass Index (BMI)	From Baseline at Week 96	BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).
Part A: Absolute Change From Parent Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	From Baseline at Week 96	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Part A: Absolute Change From Parent Study Baseline in Body Weight	From Baseline at Week 96	—
Part A: Absolute Change From Parent Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score	From Baseline at Week 96	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 A: Absolute Change From Parent Study Baseline in BMI Z-score	From Baseline at Week 96	BMI was defined as weight in kilogram (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.

Countries

Australia, Belgium, Canada, Denmark, France, Germany, Ireland, Italy, Netherlands, Spain, United Kingdom, United States

Participant flow

Recruitment details

The study was conducted as a single part study (Part A) in countries including United States (US), and the protocol for other countries was amended as a regional protocol so that participants in these countries had the opportunity to participate for up to an additional 48 weeks in Part B.

Pre-assignment details

Participants from parent study VX18-445-104 (NCT04058353) were enrolled in this study. A total of 251 participants were enrolled in this study.

Participants by arm

Arm	Count
ELX/TEZ/IVA Part A: Participants received ELX 200mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 96 weeks. Part B: Participants from certain countries participated in Part B and continued to receive ELX 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 48 weeks.	251
Total	251

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	14
Overall Study	Commercial drug is available for participants	6
Overall Study	Death	1
Overall Study	Other	6
Overall Study	Other non-compliance	2
Overall Study	Withdrawal of Consent (not due to AE)	7

Baseline characteristics

Characteristic	ELX/TEZ/IVA
Age, Continuous	37.9 years STANDARD_DEVIATION 14.4
Race/Ethnicity, Customized Black or African American	2 Participants
Race/Ethnicity, Customized Hispanic or Latino	9 Participants
Race/Ethnicity, Customized More than one race	1 Participants
Race/Ethnicity, Customized Not collected per local regulations	18 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	224 Participants
Race/Ethnicity, Customized Other	5 Participants
Race/Ethnicity, Customized White	225 Participants
Sex: Female, Male Female	124 Participants
Sex: Female, Male Male	127 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	1 / 251	0 / 84
other Total, other adverse events	223 / 251	48 / 84
serious Total, serious adverse events	38 / 251	3 / 84

Outcome results

Primary

Part A: 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 100

Population: The open label (OL) Safety Set for Part A was defined as all participants who received at least 1 dose of study drug in the OLS Part A (participants were assigned based on parent study actual treatment).

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Part A: ELX/TEZ/IVA	Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Participants with TEAEs	241 Participants
Part A: ELX/TEZ/IVA	Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Participants with SAEs	38 Participants

Secondary

Part A: Absolute Change From Parent Study Baseline in BMI Z-score

BMI was defined as weight in kilogram (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.