Clinical Trial Results:
A Phase 2, Single-Blind, Placebo-Controlled Study to Evaluate the Effect of VX-770 on Hyperpolarized Helium-3 Magnetic Resonance Imaging in Subjects With Cystic Fibrosis, the G551D Mutation, and FEV1 ≥40% Predicted
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Summary
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EudraCT number |
2017-000672-28 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
12 Feb 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Jun 2017
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First version publication date |
08 Jun 2017
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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 |
VX10-770-107
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01161537 | ||
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, United States, 02210-1862
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Public contact |
Medical Monitor, Vertex Pharmaceuticals Incorporated, 1 6173416777, medical_info@vrtx.com
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Scientific contact |
Medical Monitor, Vertex Pharmaceuticals Incorporated, 1 6173416777, medical_info@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 Jun 2013
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
12 Feb 2013
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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 VX-770 on hyperpolarized helium-3 magnetic resonance imaging (3He-MRI) in subjects aged 12 years and older with CF who have the G551D-CFTR mutation on at least 1 allele
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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 Council on Harmonization (ICH) Guideline for Good Clinical Practice (GCP).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Oct 2010
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Long term follow-up planned |
No
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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: 13
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Worldwide total number of subjects |
13
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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) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
4
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Adults (18-64 years) |
9
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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 |
Study was initiated on October 10, 2010 after first eligible subject signed informed consent form and enrolled in study. | |||||||||||||||
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Pre-assignment
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Screening details |
All results were planned to be reported separately for Part A and Part B of the study. | |||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Single blind | |||||||||||||||
Roles blinded |
Subject | |||||||||||||||
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Arms
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Are arms mutually exclusive |
No
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Arm title
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Part A: VX-770 | |||||||||||||||
Arm description |
Subjects received placebo tablets matched to VX-770 150 mg orally twice daily from Day 1 to 14 (Placebo run-in period), followed by VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), and then placebo tablets matched to VX-770 150 mg orally twice daily from Day 43 to 57 (Placebo washout period) during Part A of the study. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
VX-770
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Investigational medicinal product code |
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Other name |
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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 VX-770 150 mg film coated tablets orally twice daily from Day 15 to 42 (VX-770 treatment period).
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo tablets matched to VX-770 150 milligram (mg) orally twice daily from Day 1 to 14 (Placebo run-in period) and from Day 43 to 57 (Placebo washout period).
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Arm title
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Part B: VX-770 | |||||||||||||||
Arm description |
Subjects received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
VX-770
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Investigational medicinal product code |
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Other name |
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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 VX-770 150 mg film coated tablets orally twice daily for 48 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Part A: VX-770
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Reporting group description |
Subjects received placebo tablets matched to VX-770 150 mg orally twice daily from Day 1 to 14 (Placebo run-in period), followed by VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), and then placebo tablets matched to VX-770 150 mg orally twice daily from Day 43 to 57 (Placebo washout period) during Part A of the study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part B: VX-770
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Reporting group description |
Subjects received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Part A: VX-770
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Reporting group description |
Subjects received placebo tablets matched to VX-770 150 mg orally twice daily from Day 1 to 14 (Placebo run-in period), followed by VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), and then placebo tablets matched to VX-770 150 mg orally twice daily from Day 43 to 57 (Placebo washout period) during Part A of the study. | ||
Reporting group title |
Part B: VX-770
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Reporting group description |
Subjects received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects. | ||
Subject analysis set title |
Part A : Placebo Run in/Washout
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Subjects who received placebo tablets matched to VX-770 150 mg orally twice daily from Day 1 to 14 (Placebo run-in period) and from Day 43 to 57 (Placebo washout period) during Part A of the study were assessed between Day 1 to 14 and Day 43 to 57 of Part A.
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End point title |
Part A: Change From Baseline in Total Ventilation Defect Defined by Hyperpolarized Helium 3 Magnetic Resonance Imaging (3He-MRI) at Day 43 [1] [2] | ||||||||
End point description |
Subjects inhaled hyperpolarized helium-3 (3He) gas mixed with nitrogen to make a total volume of approximately one-third forced vital capacity (FVC) to a maximum of 1 liter and hold their breath for 20 seconds or less. Rapid magnetic resonance imaging (MRI) was performed during inhalation/exhalation and/or breath-hold. Areas of decreased ventilation were observed as ventilation defects that are visualized as decreased (and/or absent) 3He intensity in 3He-MRI. The total ventilation defect was defined as the ratio of total ventilation defect volume (L) to total lung volume (L), expressed as a percentage. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug in VX-770 treatment phase (Day 15 to 42). Full Analysis Set (FAS) included all enrolled subjects who received at least 1 dose of study drug (VX-770 or placebo) in Part A.
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End point type |
Primary
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End point timeframe |
Part A: Baseline (pre-dose Day 15), Day 43
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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 reported, inferential statistics were not planned for this primary endpoint. [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only arms which are applicable to the endpoint are reported. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Part B: Change From Baseline in Total Ventilation Defect Defined by Hyperpolarized Helium 3 Magnetic Resonance Imaging (3He-MRI) at Week 48 [3] [4] | ||||||||
End point description |
Subjects were asked to inhale hyperpolarized 3 He gas mixed with nitrogen to make a total volume of approximately one-third forced vital capacity (FVC) to a maximum of 1 liter and hold their breath for 20 seconds or less. Rapid MRI was performed during inhalation/exhalation and/or breath-hold. Areas of decreased ventilation were observed as ventilation defects that are visualized as decreased (and/or absent) 3He intensity in 3He MRI. The total ventilation defect was defined as the ratio of total ventilation defect volume (L) to total lung volume (L), expressed as a percentage. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug in Part B (48 weeks). FAS included all enrolled subjects who received at least 1 dose of study drug (VX-770) in Part B.
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End point type |
Primary
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End point timeframe |
Part B: Baseline (Day -1), Week 48
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| Notes [3] - 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 reported, inferential statistics were not planned for this primary endpoint. [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only arms which are applicable to the endpoint are reported. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Part A: Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs [5] | |||||||||||||||||||||
End point description |
AE: Any adverse change from subject’s baseline condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Related AEs includes all AEs for which causality was either related to study drug or possibly related to study drug. Safety analysis set includes all enrolled subjects who received at least 1 dose of study drug (VX-770 or placebo) in Part A. Data was reported as per intervention received (Placebo [Placebo Run in/Washout] or VX-770 [VX-770 Treatment]).
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End point type |
Secondary
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End point timeframe |
Part A: Day 1 up to Day 57
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| Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only arms which are applicable to the endpoint are reported. |
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Part A: Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Day 43 [6] | ||||||||
End point description |
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Predicted FEV1 (for age, gender, and height) was calculated using the Knudson method. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug in VX-770 treatment phase (Day 15 to 42). FAS included all enrolled subjects who received at least 1 dose of study drug (VX-770 or placebo) in Part A.
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End point type |
Secondary
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End point timeframe |
Part A: Baseline (pre-dose Day 15), Day 43
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| Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only arms which are applicable to the endpoint are reported. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Part A: Absolute Change From Baseline in Sweat Chloride at Day 43 [7] | ||||||||
End point description |
Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug in VX-770 treatment phase (Day 15 to 42). FAS included all enrolled subjects who received at least 1 dose of study drug (VX-770 or placebo) in Part A.
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End point type |
Secondary
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End point timeframe |
Part A: Baseline (pre-dose Day 15), Day 43
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| Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only arms which are applicable to the endpoint are reported. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Part A: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score At Day 43 [8] | ||||||||
End point description |
The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug in VX-770 treatment phase (Day 15 to 42). FAS included all enrolled subjects who received at least 1 dose of study drug (VX-770 or placebo) in Part A.
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End point type |
Secondary
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End point timeframe |
Baseline (pre-dose Day 15), Day 43
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| Notes [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only arms which are applicable to the endpoint are reported. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Part B: Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs [9] | ||||||||||||
End point description |
AE: any adverse change from subject’s baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Safety analysis set included all enrolled subjects who received at least 1 dose of study drug (VX-770 or placebo) in Part B.
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End point type |
Secondary
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End point timeframe |
Part B: Day 1 up to Week 48
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| Notes [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only arms which are applicable to the endpoint are reported. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Part B: Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 48 [10] | ||||||||
End point description |
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Predicted FEV1 (for age, gender, and height) was calculated using the Knudson method. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug in Part B (48 weeks). FAS included all enrolled subjects who received at least 1 dose of study drug (VX-770) in Part B. Here, "Number of subjects analyzed" signifies those subjects who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Part B: Baseline (Day -1), Week 48
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| Notes [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only arms which are applicable to the endpoint are reported. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Part B: Absolute Change From Baseline in Sweat Chloride at Week 48 [11] | ||||||||
End point description |
Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug in Part B (48 weeks). FAS included all enrolled subjects who received at least 1 dose of study drug (VX-770) in Part B. Here, "Number of subjects analyzed" signifies those subjects who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Part B: Baseline (Day -1), Week 48
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| Notes [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only arms which are applicable to the endpoint are reported. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Part B: Absolute Change From Baseline in in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score At Week 48 [12] | ||||||||
End point description |
The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug in Part B (48 weeks). FAS included all enrolled subjects who received at least 1 dose of study drug (VX-770) in Part B. Here, "Number of subjects analyzed" signifies those subjects who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Part B: Baseline (Day -1), Week 48
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| Notes [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only arms which are applicable to the endpoint are reported. |
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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 |
Part A: Day 1 through Day 57; Part B: Day 1 through Week 48
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Adverse event reporting additional description |
Subject with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
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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 |
12.0
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Reporting groups
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Reporting group title |
Part A: Placebo Run in/Washout
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Reporting group description |
Subjects who received placebo tablets matched to VX-770 150 mg orally twice daily from Day 1 to 14 (Placebo run-in period) and from Day 43 to 57 (Placebo washout period) during Part A of the study were assessed between Day 1 to 14 and Day 43 to 57 of Part A. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part A: VX-770 Treatment
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Reporting group description |
Subjects who received VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), during Part A of the study were assessed between Day 15 to 42 of Part A. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part B: VX-770 Treatment
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Reporting group description |
Subjects who received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study were assessed between Day 1 to Week 48 of Part B. Part B included subjects from Part A and newly enrolled subjects. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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18 Jun 2010 |
- The Removal of Subjects section and the section for Elevation of Liver Function Test Parameters were revised. |
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10 Jan 2011 |
- Interim analysis of data added. |
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04 Mar 2011 |
- Limit on FEV1 severity categories removed from the protocol to allow evaluation of additional subjects. |
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16 May 2011 |
- Identified the original components of the study as “Part A” to distinguish these from the new, open-label, 48-week part of the study identified as “Part B", which was added to evaluate the long-term effect of VX-770 on 3 He-MRI. |
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03 Aug 2011 |
- Age limit for part B of the study was changed. |
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20 Mar 2012 |
- Screening ophthalmologic examination was added to Part B. |
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01 Nov 2012 |
- Total study duration was shortened; - Commercially available VX-770 (Kalydeco™) was added to the list of prohibited medications. |
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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 | |||
