Clinical Trial Results:
A Phase 3, 2-Arm, Open-label Study to Evaluate the Safety and Pharmacodynamics of Long-term Ivacaftor Treatment in Subjects With Cystic Fibrosis Who Are Less Than 24 Months of Age at Treatment Initiation and Have an Approved Ivacaftor-Responsive Mutation
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Summary
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EudraCT number |
2017-001379-21 |
Trial protocol |
GB IE DE |
Global end of trial date |
02 Oct 2023
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Results information
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Results version number |
v2(current) |
This version publication date |
09 Nov 2024
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First version publication date |
14 Apr 2024
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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 |
VX15-770-126
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03277196 | ||
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-000335-PIP01-08 | ||
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 |
26 Oct 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
02 Oct 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Oct 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 of long-term ivacaftor treatment in subjects with CF who are less than (<) 24 months of age at treatment initiation and have an approved ivacaftor-responsive mutation.
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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 |
16 Aug 2017
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
28 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 Kingdom: 19
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Country: Number of subjects enrolled |
Germany: 1
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Country: Number of subjects enrolled |
Ireland: 8
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Country: Number of subjects enrolled |
United States: 52
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Country: Number of subjects enrolled |
Australia: 4
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Country: Number of subjects enrolled |
Canada: 2
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Worldwide total number of subjects |
86
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EEA total number of subjects |
9
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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) |
86
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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 |
This study was planned to include 2 arms: an ivacaftor (IVA) arm (open-label, 96-week treatment period) and an observational arm. However, there were no subjects enrolled in the observational arm. A total of 86 subjects were enrolled in the Ivacaftor arm. | ||||||||||||||||||||
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Pre-assignment
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Screening details |
Rollover Subjects (who completed parent study VX15-770-124 [NCT02725567] Part B or Part A/B) and IVA-naïve subjects (who participated in study VX15-770-124 Part A only or who did not participate in VX15-770-124 and were <24 months of age at the Day 1 of current study [VX15-770-126]) were enrolled in this study. | ||||||||||||||||||||
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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 |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||
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Arms
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Arm title
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IVA treatment | ||||||||||||||||||||
Arm description |
Subjects less than (<) 24 months of age and weighing 5 to less than (<) 7 kilogram (kg) received 25 mg IVA every 12 hours (q12h), 7 to <14 kg received 50 mg IVA q12h, and those weighing 14 to <25 kg received 75 mg IVA q12h. Subjects more than or equal (>=) 24 months of age and weighing <14 kg received 50 mg IVA q12h, and those weighing more than or equal to (>=)14 kg received 75 mg IVA q12h in the treatment period for up to 96 weeks. Doses were determined based on safety and pharmacokinetic (PK) data from parent study, age and weight. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
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 |
Granules
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received IVA dose 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 86 subjects were enrolled in the study. However, only 38 subjects rolled over from the parent study VX15-770-124 (NCT02725567) Part B or Part A/B study to this study, and the rest of the subjects were enrolled in the IVA naive group. [2] - 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 86 subjects were enrolled in the study. However, only 48 subjects were enrolled in the IVA naive group. Subjects in IVA naive group are those who participated in study VX15-770-124 Part A only or who did not participate in VX15-770-124. |
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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 data was analyzed on safety set which is defined as all subjects who received at least 1 dose of study drug. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
IVA treatment
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Reporting group description |
Subjects less than (<) 24 months of age and weighing 5 to less than (<) 7 kilogram (kg) received 25 mg IVA every 12 hours (q12h), 7 to <14 kg received 50 mg IVA q12h, and those weighing 14 to <25 kg received 75 mg IVA q12h. Subjects more than or equal (>=) 24 months of age and weighing <14 kg received 50 mg IVA q12h, and those weighing more than or equal to (>=)14 kg received 75 mg IVA q12h in the treatment period for up to 96 weeks. Doses were determined based on safety and pharmacokinetic (PK) data from parent study, age and weight. | ||
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End point title |
Safety and Tolerability as Assessed by Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs [1] | ||||||||||
End point description |
Safety Set included all subjects who received at least 1 dose of study drug in this study.
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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 this endpoint. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Absolute Change in Sweat Chloride (SwCl) | ||||||||
End point description |
Sweat samples were collected using an approved collection device. The Full Analysis Set (FAS) included all subjects who were enrolled and received at least 1 post baseline efficacy assessment in this study. Here “Number of subjects Analyzed” signifies those subjects who were evaluated for this endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline at Week 96
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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 120
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Adverse event reporting additional description |
Safety Set included all subjects who received at least 1 dose of study drug in this study.
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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 |
26.1
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Reporting groups
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Reporting group title |
IVA treatment
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Reporting group description |
Subjects <24 months of age and weighing 5 <7 kg received 25 mg IVA q12h, 7 to <14 kg received 50 mg IVA q12h, and those weighing 14 to <25 kg received 75 mg IVA q12h. Subjects >=24 months of age and weighing <14 kg received 50 mg IVA q12h, and those weighing >=14 kg received 75 mg IVA q12h in the treatment period for up to 96 weeks. Doses were determined based on safety and PK data from parent study, age and weight. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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05 Oct 2017 |
Amended to remove study visit at Week 104, as the 2 year treatment period concludes at Week 96; For subjects not from Study 124 Part B, revised inclusion criterion to change lower weight bound at screening to comply with request from Regulatory Health Authority. Revised study population and inclusion criteria to include subjects with CF <24 months of age who have an ivacaftor responsive CFTR mutation on at least 1 allele. |
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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 | |||
