Clinical Trial Results:
A Phase 3b Open-label Study Evaluating the Effects of Elexacaftor/Tezacaftor/Ivacaftor on Cough and Physical Activity in Cystic Fibrosis Subjects 12 Years of Age and Older Who Are Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
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Summary
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EudraCT number |
2021-001628-16 |
Trial protocol |
ES BE |
Global end of trial date |
26 Jul 2022
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Results information
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Results version number |
v2(current) |
This version publication date |
20 Oct 2023
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First version publication date |
08 Feb 2023
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
VX20-445-126
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04969224 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Vertex Pharmaceuticals Incorporated
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Sponsor organisation address |
50 Northern Avenue, Boston, Massachusetts, United States,
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Public contact |
Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617-341-6777, medicalinfo@vrtx.com
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Scientific contact |
Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617-341-6777, medicalinfo@vrtx.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
14 Sep 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
26 Jul 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Jul 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the effects of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on cough and physical activity using wearable technology in Cystic Fibrosis(CF) subjects.
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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).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
12 Oct 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 7
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Country: Number of subjects enrolled |
Belgium: 31
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Country: Number of subjects enrolled |
Canada: 7
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Country: Number of subjects enrolled |
Australia: 37
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Worldwide total number of subjects |
82
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EEA total number of subjects |
38
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
24
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Adults (18-64 years) |
58
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||
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Pre-assignment
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Screening details |
This study was conducted in subjects with cystic fibrosis, aged 12 years and older, who are heterozygous for the F508del mutation and the minimal function mutation (F/MF) genotypes. A 2-week baseline period was used to establish baseline cough and activity patterns prior to the first dose of study drug. | ||||||||||
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Period 1
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Period 1 title |
Overall Period
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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ELX/TEZ/IVA | ||||||||||
Arm description |
Subjects received elexacaftor (ELX) 200 milligram (mg) once daily (qd)/ tezacaftor (TEZ) 100 mg qd/ ivacator (IVA) 150 mg every 12 hours (q12h) in the treatment period approximately 13 weeks. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
ELX/TEZ/IVA
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Investigational medicinal product code |
VX-445/VX-661/VX-770
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Other name |
elexacaftor/tezacaftor/ivacaftor
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received ELX/TEZ/IVA FDC combination once daily in the morning.
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Investigational medicinal product name |
IVA
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Investigational medicinal product code |
VX-770
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Other name |
ivacaftor
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received IVA dose once daily in the evening.
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: A total 82 subjects were enrolled in the study. One subject in enrolled but did not dose in this study. Therefore, data for 81 subjects are reported in the subject disposition and baseline characteristics sections. |
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Baseline characteristics reporting groups
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Reporting group title |
Overall Period
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Reporting group description |
Subjects received ELX 200 mg qd/ TEZ 100 mg qd/IVA) 150 mg q12h in the treatment period approximately 13 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
ELX/TEZ/IVA
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Reporting group description |
Subjects received elexacaftor (ELX) 200 milligram (mg) once daily (qd)/ tezacaftor (TEZ) 100 mg qd/ ivacator (IVA) 150 mg every 12 hours (q12h) in the treatment period approximately 13 weeks. | ||
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End point title |
Percent Reduction From Baseline in Cough Frequency (cough events per day) to the Average of Week 8 Through Week 12 [1] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline, Week 8 through Week 12
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| 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: Participants’ post-baseline values were compared to their baseline values with a mixed model for repeated measures with change from baseline at each post-baseline visit on the natural log scale as the dependent variable. The primary result obtained from the model was the estimated percent reduction in cough frequency from baseline to the average of Week 8 through Week 12, i.e. 100% × (1-(exp (LS mean)). |
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| No statistical analyses for this end point | |||||||||
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End point title |
Absolute Change From Baseline in Total Step Count per day to the Average of Week 8 Through Week 12 | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8 through Week 12
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Day 1 up to Week 17
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25.0
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Reporting groups
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Reporting group title |
ELX/TEZ/IVA
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Reporting group description |
Subjects received ELX 200 mg qd/ TEZ 100 mg qd/IVA 150 mg q12h in the treatment period approximately 13 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
