Clinical Trial Results:
A Randomized, Double-blind, Placebo-controlled, Crossover Study to Evaluate the Efficacy of Ivacaftor in Subjects with Cystic Fibrosis Who are 6 Years of Age and Older and Have Either a 3849 + 10KB C→T or D1152H-CFTR Mutation
|
Summary
|
|
EudraCT number |
2017-000457-39 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
18 Dec 2018
|
|
Results information
|
|
Results version number |
v1 |
This version publication date |
04 Jul 2019
|
First version publication date |
04 Jul 2019
|
Other versions |
v2 |
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 |
VX16-770-127
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT03068312 | ||
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) |
No
|
||
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 |
22 Jan 2019
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
18 Dec 2018
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
18 Dec 2018
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
To evaluate the efficacy of ivacaftor (IVA) treatment in subjects with cystic fibrosis (CF) 6 years of age and older who have a 3849 + 10KB C→T or D1152H CF transmembrane conductance regulator gene (CFTR) mutation.
|
||
Protection of trial subjects |
The study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki and the International Council on Harmonization (ICH) Guideline for Good Clinical Practice (GCP).
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
18 Jul 2017
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Israel: 38
|
||
Worldwide total number of subjects |
38
|
||
EEA total number of subjects |
0
|
||
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) |
4
|
||
Adolescents (12-17 years) |
4
|
||
Adults (18-64 years) |
30
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
||||||||||
|
Recruitment
|
||||||||||
Recruitment details |
- | |||||||||
|
Pre-assignment
|
||||||||||
Screening details |
This study was conducted in subjects with CF. | |||||||||
|
Period 1
|
||||||||||
Period 1 title |
Overall Period
|
|||||||||
Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
|
|||||||||
Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Carer, Assessor | |||||||||
|
Arms
|
||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||
|
Arm title
|
Sequence 1: First IVA Then Placebo | |||||||||
Arm description |
Subjects received IVA for 8 weeks in treatment period 1 followed by placebo matched to IVA for 8 weeks in treatment period 2. A washout period of 8 weeks was maintained between the 2 treatment periods. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
IVA
|
|||||||||
Investigational medicinal product code |
VX-770
|
|||||||||
Other name |
Ivacaftor
|
|||||||||
Pharmaceutical forms |
Tablet
|
|||||||||
Routes of administration |
Oral use
|
|||||||||
Dosage and administration details |
Subjects received IVA 150 milligram (mg) every 12 hours.
|
|||||||||
Investigational medicinal product name |
Placebo (matched to IVA)
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||
Routes of administration |
Oral use
|
|||||||||
Dosage and administration details |
Subjects received placebo matched to IVA every 12 hours.
|
|||||||||
|
Arm title
|
Sequence 2: First Placebo Then IVA | |||||||||
Arm description |
Subjects received placebo matched to IVA for 8 weeks in treatment period 1 followed by IVA for 8 weeks in treatment period 2. A washout period of 8 weeks was maintained between the 2 treatment periods. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Placebo (Matched to IVA)
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||
Routes of administration |
Oral use
|
|||||||||
Dosage and administration details |
Subjects received placebo matched to IVA every 12 hours.
|
|||||||||
Investigational medicinal product name |
IVA
|
|||||||||
Investigational medicinal product code |
VX-770
|
|||||||||
Other name |
Ivacaftor
|
|||||||||
Pharmaceutical forms |
Tablet
|
|||||||||
Routes of administration |
Oral use
|
|||||||||
Dosage and administration details |
Subjects received IVA 150 mg every 12 hours.
|
|||||||||
|
||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence 1: First IVA Then Placebo
|
||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received IVA for 8 weeks in treatment period 1 followed by placebo matched to IVA for 8 weeks in treatment period 2. A washout period of 8 weeks was maintained between the 2 treatment periods. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence 2: First Placebo Then IVA
|
||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received placebo matched to IVA for 8 weeks in treatment period 1 followed by IVA for 8 weeks in treatment period 2. A washout period of 8 weeks was maintained between the 2 treatment periods. | ||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Sequence 1: First IVA Then Placebo
|
||
Reporting group description |
Subjects received IVA for 8 weeks in treatment period 1 followed by placebo matched to IVA for 8 weeks in treatment period 2. A washout period of 8 weeks was maintained between the 2 treatment periods. | ||
Reporting group title |
Sequence 2: First Placebo Then IVA
|
||
Reporting group description |
Subjects received placebo matched to IVA for 8 weeks in treatment period 1 followed by IVA for 8 weeks in treatment period 2. A washout period of 8 weeks was maintained between the 2 treatment periods. | ||
Subject analysis set title |
Placebo
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All subjects who received placebo matched to IVA for 8 weeks in treatment period 1 or 2.
|
||
Subject analysis set title |
IVA
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All subjects who received IVA for 8 weeks in treatment period 1 or 2.
|
||
|
|||||||||||||
End point title |
Change in Lung Clearance Index 2.5 | ||||||||||||
End point description |
|||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
From baseline through 8 weeks
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs IVA | ||||||||||||
Statistical analysis description |
The "number of subjects included in analysis" was 37 instead of 74 because this study has a cross-over design and same subjects received both the interventions. The number "74" is auto-calculated as the sum of numbers presented in 2 comparison groups and is appearing due to EudraCT database format constraints.
|
||||||||||||
Comparison groups |
Placebo v IVA
|
||||||||||||
Number of subjects included in analysis |
74
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
Mixed-effects model for repeated measure | ||||||||||||
Parameter type |
Least squares mean difference | ||||||||||||
Point estimate |
-0.66
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.1 | ||||||||||||
upper limit |
-0.21 | ||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From first dose of study drug up to safety follow-up visit
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All subjects who received placebo matched to IVA for 8 weeks in treatment period 1 or 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ivafactor
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All subjects who received IVA for 8 weeks in treatment period 1 or 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
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 | |||
