Clinical Trial Results:
A Phase 3, Open-label Study Evaluating the Long-term Safety and Efficacy of VX-445/TEZ/IVA Combination Therapy in Subjects With Cystic Fibrosis Who Are 6 Years of Age and Older
|
Summary
|
|
EudraCT number |
2019-001827-11 |
Trial protocol |
GB IE |
Global end of trial date |
24 Feb 2024
|
|
Results information
|
|
Results version number |
v2(current) |
This version publication date |
05 Jun 2025
|
First version publication date |
07 Sep 2024
|
Other versions |
v1 |
Version creation reason |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
VX19-445-107
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT04183790 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Vertex Pharmaceuticals Incorporated
|
||
Sponsor organisation address |
50 Northern Avenue, Boston, Massachusetts, United States,
|
||
Public contact |
Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617-341-6777, medicalinfo@vrtx.com
|
||
Scientific contact |
Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617-341-6777, medicalinfo@vrtx.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-002324-PIP01-17 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
20 Mar 2024
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
24 Feb 2024
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
24 Feb 2024
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
To evaluate the long-term safety and tolerability of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are 6 years of age and older
|
||
Protection of trial subjects |
The study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki and the International Conference on Harmonization (ICH) Guideline for Good Clinical Practice (GCP).
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Feb 2020
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
45 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United Kingdom: 6
|
||
Country: Number of subjects enrolled |
Ireland: 5
|
||
Country: Number of subjects enrolled |
Canada: 6
|
||
Country: Number of subjects enrolled |
Australia: 8
|
||
Country: Number of subjects enrolled |
United States: 39
|
||
Worldwide total number of subjects |
64
|
||
EEA total number of subjects |
5
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
64
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||||||
Recruitment details |
The study was conducted in two parts, Part A and Part B. Subjects of both Parts A and B received the same treatment (ELX/TEZ/IVA). Therefore, results were planned to be collected and analysed for the overall population of the study. A total of 64 subjects were enrolled in this study. | ||||||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||||||
Screening details |
Subjects who completed Part B of parent study VX18-445-106 (NCT03691779) and did not permanently discontinue study drug in the parent study had the opportunity to enroll in this study. | ||||||||||||||||||||||
|
Period 1
|
|||||||||||||||||||||||
Period 1 title |
Overall Period
|
||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||||
|
Arms
|
|||||||||||||||||||||||
|
Arm title
|
ELX/TEZ/IVA | ||||||||||||||||||||||
Arm description |
Subjects greater than or equal to (≥) 6 years and less than (<) 12 years of age and weighing <30 kilograms (kg) received ELX (elexacaftor) 100 milligram (mg) once daily (qd) /TEZ (tezacaftor) 50 mg qd/IVA (ivacaftor) 75 mg every 12 hours (q12h) and those weighing (≥) 30 kg received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg in the treatment period for up to 192 weeks. Subjects ≥ 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. | ||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||
Investigational medicinal product name |
Elexacaftor/Tezacaftor/Ivacaftor
|
||||||||||||||||||||||
Investigational medicinal product code |
VX-445/VX-661/VX-770
|
||||||||||||||||||||||
Other name |
ELX/TEZ/IVA
|
||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||
Dosage and administration details |
Subjects received ELX/TEZ/IVA fixed dose combination (FDC) once daily in the morning.
|
||||||||||||||||||||||
Investigational medicinal product name |
Ivacaftor
|
||||||||||||||||||||||
Investigational medicinal product code |
VX-770
|
||||||||||||||||||||||
Other name |
IVA
|
||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||
Dosage and administration details |
Subjects received IVA once daily in the evening.
|
||||||||||||||||||||||
|
|||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Overall Period
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Baseline data was analysed on Full analysis set (FAS) which is defined as all subjects who received at least 1 dose of study drug in this study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
ELX/TEZ/IVA
|
||
Reporting group description |
Subjects greater than or equal to (≥) 6 years and less than (<) 12 years of age and weighing <30 kilograms (kg) received ELX (elexacaftor) 100 milligram (mg) once daily (qd) /TEZ (tezacaftor) 50 mg qd/IVA (ivacaftor) 75 mg every 12 hours (q12h) and those weighing (≥) 30 kg received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg in the treatment period for up to 192 weeks. Subjects ≥ 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. | ||
|
|||||||||||
End point title |
Safety and Tolerability as Assessed by Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [1] | ||||||||||
End point description |
The Open-Label Extension Safety Set (OLE-SS) included all subjects who had received at least 1 dose of study drug in the study.
|
||||||||||
End point type |
Primary
|
||||||||||
End point timeframe |
Day 1 up to Week 196
|
||||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistics were planned. No statistical comparisons were planned for the primary safety endpoint. |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||
End point title |
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | ||||||||
End point description |
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data for this end point was planned to be collected and analysed for the overall ELX/TEZ/IVA TC arm irrespective of Part A and B separately. Open label Extension Full Analysis Set (OLE FAS) included all enrolled subjects who have received at least 1 dose of study drug in the OLE study. Here "Number of subjects analysed" signifies those subjects who were evaluated for this specific endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From Baseline up to Week 192
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Absolute Change in Sweat Chloride (SwCl) | ||||||||
End point description |
Sweat samples were collected using an approved collection device. Data for this end point was planned to be collected and analysed for the overall ELX/TEZ/IVA TC arm irrespective of Part A and B separately. OLE FAS. Here "Number of subjects analysed" signifies those subjects who were evaluated for this specific endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From Baseline up to Week 192
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score | ||||||||
End point description |
The CFQ-R is a validated subject-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Data for this end point was planned to be collected and analysed for the overall ELX/TEZ/IVA TC arm irrespective of Part A and B separately. OLE FAS. Here "Number of subjects analysed" signifies those subjects who were evaluated for this specific endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From Baseline up to Week 192
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Absolute Change in Body Mass Index (BMI) | ||||||||
End point description |
BMI was defined as weight in kilogram (kg) divided by squared height in meters (m^2). Data for this end point was planned to be collected and analysed for the overall ELX/TEZ/IVA TC arm irrespective of Part A and B separately. OLE FAS. Here "Number of subjects analysed" signifies those subjects who were evaluated for this specific endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From Baseline up to Week 192
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Absolute Change in BMI-for-age Z-score | ||||||||
End point description |
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. Data for this end point was planned to be collected and analysed for the overall ELX/TEZ/IVA TC arm irrespective of Part A and B separately. OLE FAS. Here "Number of subjects analysed" signifies those subjects who were evaluated for this specific endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From Baseline up to Week 192
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Number of Subjects with Pulmonary Exacerbations (PEx) for 106/107 | ||||||||
End point description |
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. The Cumulative TC Set includes subjects who enrolled and received at least one dose of study drug during the parent study (445-106 Part B) and/or received at least one dose of study drug during this OLE Study. Data for this end point was planned to be collected and analyzed for the overall ELX/TEZ/IVA TC arm irrespective of Part A and B separately. Here “Number of subjects analysed” signifies those subjects who were enrolled in this study only and evaluated for this specific end point. Here “n” signifies Cumulative TC set subjects who were evaluable for this endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From Baseline up to Week 192
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||
End point title |
Number of CF-related Hospitalizations for 106/107 | ||||||||||
End point description |
The total number of CF related hospitalization (Planned + Unplanned) events across all subjects were reported. The Cumulative TC Set. Data for this end point was planned to be collected and analyzsd for the overall ELX/TEZ/IVA TC arm irrespective of Part A and B separately. Here “Number of subjects analysed” signifies those subjects who were enrolled in this study only and evaluated for this specific end point. Here “n” signifies Cumulative TC set subjects who were evaluable for this endpoint.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
From Baseline up to Week 192
|
||||||||||
|
|||||||||||
| Notes [2] - 64 subjects enrolled in the 445-107 and 2 subjects from parent study were included for this analysis |
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||
End point title |
Absolute Change in Lung Clearance Index 2.5 (LCI2.5) | ||||||||
End point description |
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. Data for this outcome measure was planned to be collected and analysed for the overall ELX/TEZ/IVA TC arm irrespective of Part A and B separately. OLE FAS. Here "Number of subjects analysed" signifies those subjects who were evaluated for this specific endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From Baseline up to Week 192
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Absolute Change in Weight | ||||||||
End point description |
Data for this endpoint was planned to be collected and analysed for the overall ELX/TEZ/IVA TC arm irrespective of Part A and B separately. OLE FAS. Here "Number of subjects analysed" signifies those subjects who were evaluated for this specific endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From Baseline up to Week 192
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Absolute Change in Weight-for-age Z-score | ||||||||
End point description |
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. Data for this end point was planned to be collected and analysed for the overall ELX/TEZ/IVA TC arm irrespective of Part A and B separately. OLE FAS. Here "Number of subjects analysed" signifies those subjects who were evaluated for this specific endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From Baseline up to Week 192
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Absolute Change in Height | ||||||||
End point description |
Data for this end point was planned to be collected and analysed for the overall ELX/TEZ/IVA TC arm irrespective of Part A and B separately. OLE FAS. Here "Number of subjects analysed" signifies those subjects who were evaluated for this specific endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From Baseline up to Week 192
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Absolute Change in Height-for-age Z-score | ||||||||
End point description |
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. Data for this end point was planned to be collected and analysed for the overall ELX/TEZ/IVA TC arm irrespective of Part A and B separately. OLE FAS. Here "Number of subjects analysed" signifies those subjects who were evaluated for this specific endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From Baseline up to Week 192
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Day 1 up to Week 196
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Safety set included all subjects who received at least 1 dose of study drug.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
ELX/TEZ/IVA
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects ≥6 years and <12 years of age and weighing <30kg 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 to 192 weeks. Subjects ≥ 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
10 Jun 2021 |
Amended to extend treatment period by adding Part B (additional 96 weeks of treatment duration) and updated monitoring text to include flexibility for remote monitoring.
|
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
