Clinical Trial Results:
A Phase 3b Open-label Study to Assess the Effect of Elexacaftor/Tezacaftor/Ivacaftor on Glucose Tolerance in Cystic Fibrosis Subjects with Abnormal Glucose Metabolism
Summary
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EudraCT number |
2020-003170-44 |
Trial protocol |
BE CZ FR NL IT |
Global end of trial date |
14 Jul 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Jan 2023
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First version publication date |
29 Jan 2023
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Other versions |
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 |
VX19-445-117
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04599465 | ||
WHO universal trial number (UTN) |
- | ||
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 |
19 Aug 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 Jul 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
14 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 effect of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) on glucose tolerance in Cystic Fibrosis (CF) subjects with impaired glucose tolerance (IGT) or CF-related diabetes (CFRD)
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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 |
15 Jan 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 |
Australia: 11
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Country: Number of subjects enrolled |
Netherlands: 9
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Country: Number of subjects enrolled |
Spain: 14
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Country: Number of subjects enrolled |
Belgium: 7
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Country: Number of subjects enrolled |
Czechia: 3
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Country: Number of subjects enrolled |
France: 13
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Country: Number of subjects enrolled |
Italy: 12
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Worldwide total number of subjects |
69
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EEA total number of subjects |
58
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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) |
19
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Adults (18-64 years) |
50
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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 |
- | ||||||||||||
Pre-assignment
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Screening details |
This study was conducted in subjects with CF aged 12 years and older who are heterozygous for the F508del mutation and a minimal function mutation (F/MF genotypes), with abnormal glucose metabolism. | ||||||||||||
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 | ||||||||||||
Arms
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Arm title
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ELX/TEZ/IVA | ||||||||||||
Arm description |
Subjects received ELX/TEZ/IVA fixed dose combination (FDC) in the morning and ivacaftor (IVA) in the evening. | ||||||||||||
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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Baseline characteristics reporting groups
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Reporting group title |
Overall Period
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Reporting group description |
Subjects received ELX/TEZ/IVA fixed dose combination (FDC) in the morning and ivacaftor (IVA) in the evening. | |||||||||||||||||||||||||||||||||||||||
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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 ELX/TEZ/IVA fixed dose combination (FDC) in the morning and ivacaftor (IVA) in the evening. |
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End point title |
Change From Baseline in 2-hour Blood Glucose Levels Following an Oral Glucose Tolerance Test (OGTT) to the Average of Week 36 and Week 48 [1] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline, Week 36 and 48
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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: This is a single arm study, and thus no between-group comparisons were planned. However, participants’ post-baseline values were compared to their pre-treatment baseline values with a mixed model for repeated measures (MMRM) with change from baseline in 2-hour post-OGTT blood glucose levels at each post-baseline visit as the dependent variable. The primary result obtained from the model was the estimated mean change from baseline to the average of Week 36 and Week 48. |
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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 52
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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/TEZ/IVA fixed dose combination (FDC) in the morning and ivacaftor (IVA) in the evening. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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22 Sep 2020 |
Removed option for use of remote measures at certain study visits such that those visits are to be performed in the clinic; clarified different glomerular filtration rates for subjects ≥18 years of age and subjects <18 years of age; clarified that during in-clinic visits, spirometry assessments may be performed on more than 1 spirometer, as applicable; removed sweat chloride assessment at Week 4. |
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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 |