Clinical Trial Results:
A Phase 3, Open-label, and Rollover Study to Evaluate the Long-term Safety and Tolerability of Lumacaftor/Ivacaftor Treatment in Subjects With Cystic Fibrosis Who Are Homozygous for F508del and 12 to <24 Months of Age at Treatment Initiation
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Summary
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EudraCT number |
2023-000946-41 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
22 Aug 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Mar 2024
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First version publication date |
06 Mar 2024
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Other versions |
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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 |
VX19-809-124
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04235140 | ||
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) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001582-PIP01-13 | ||
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 |
18 Sep 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
22 Aug 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Aug 2023
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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 safety and tolerability of long-term lumacaftor/ivacaftor (LUM/IVA) treatment in subjects with cystic fibrosis (CF), who are homozygous for F508del and 12 to less than (<) 24 months of age at treatment initiation.
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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 |
24 Feb 2020
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
30 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
United States: 39
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Country: Number of subjects enrolled |
Canada: 13
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Worldwide total number of subjects |
52
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EEA total number of subjects |
0
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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) |
52
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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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 CF aged 12 through less than 24 months of age at treatment initiation who are homozygous for F508del and subjects who completed the 24-week treatment period along with the safety follow-up in study VX16-809-122 (NCT03601637) part B. | ||||||||||||||||||||
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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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LUM/IVA | ||||||||||||||||||||
Arm description |
Subjects weighing 7 to less than (<) 9 kilograms (kg) received LUM 75 milligrams (mg)/IVA 94 mg fixed-dose combination (FDC) every 12 hours (q12h) and those weighing 9 to <14 kg received LUM 100 mg/IVA 125 mg q12h for 96 weeks. Subjects weighing greater than or equal to (>=)14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 96 weeks. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
LUM/IVA
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Investigational medicinal product code |
VX-809/VX-770
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Other name |
Lumacaftor/Ivacaftor
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Pharmaceutical forms |
Granules
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received LUM/IVA FDC every 12 hours.
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| Notes [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: A total of 52 subjects were enrolled in the study. However, only 39 subjects rolled over from the VX16-809-122 study to this study, and the rest of the subjects were enrolled in the LUM-IVA naive group. Subjects in LUMN-IVA naive group are those who did not participate in Study VX16-809-122. |
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Baseline characteristics reporting groups
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Reporting group title |
Overall Period
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Reporting group description |
Baseline value was defined as the most recent non-missing measurement (scheduled or unscheduled) collected on or before the first dose of LUM/IVA in Study 124. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
LUM/IVA
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Reporting group description |
Subjects weighing 7 to less than (<) 9 kilograms (kg) received LUM 75 milligrams (mg)/IVA 94 mg fixed-dose combination (FDC) every 12 hours (q12h) and those weighing 9 to <14 kg received LUM 100 mg/IVA 125 mg q12h for 96 weeks. Subjects weighing greater than or equal to (>=)14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 96 weeks. | ||
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End point title |
Safety and tolerability as assessed by the number of adverse events (AEs) and serious adverse events (SAEs) [1] | ||||||||||
End point description |
Safety set included all subjects who are exposed to any amount of study drug in Study 124.
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End point type |
Primary
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End point timeframe |
Day 1 up to Week 120
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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: Only descriptive statistics were planned. No statistical comparisons were planned for the primary safety endpoint. |
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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 to Week 120
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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 |
26.0
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Reporting groups
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Reporting group title |
LUM/IVA
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Reporting group description |
Subjects weighing 7 to < 9 kg at Day 1 received LUM 75 mg/IVA 94 mg FDC q12h and those weighing 9 to <14 kg at Day 1 received LUM 100 mg/IVA 125 mg q12h for 96 weeks. Subjects weighing >=14 kg at Day 1 received LUM 150 mg/IVA 188 mg FDC q12h for 96 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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Date |
Amendment |
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12 Feb 2021 |
Amended to add the new dose of LUM 75 mg/IVA 94 mg and adjusted the lower weight bound for the LUM 100 mg/IVA 125 mg dose. |
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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 | |||
