Back to resultsA Study to Evaluate the Efficacy and Safety of Lumacaftor in Combination With Ivacaftor in Subjects With CF, Homozygous for the F508del-CFTR Mutation
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
VX-809
Placebo
VX-770
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis
Eligibility Criteria
Inclusion Criteria:
- Subjects who weigh ≥15 kg without shoes a the Screening Visit
- Subjects with confirmed diagnosis of CF at the Screening Visit.
- Subjects who are homozygous for the F508del CFTR mutation
- Subjects with ppFEV1 of ≥70 percentage points adjusted for age, sex, and height
- Subjects with a screening LCI2.5 result greater than or equal to 7.5
Exclusion Criteria:
- History of any comorbidity reviewed at the Screening Visit that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject.
- Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject
- Clinically significant abnormalities in hemoglobin, liver function, or renal function at the Screening Visit.
- An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before Day 1
- History of solid organ or hematological transplantation at the Screening Visit
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
LUM/IVA
Placebo
Arm Description
Fixed-dose combination with lumacaftor (LUM) 200 mg every 12 hours (q12h)/ ivacaftor (IVA) 250 mg q12h
Matching placebo q12h
Outcomes
Primary Outcome Measures
Absolute Change From Baseline in Lung Clearance Index 2.5 (LCI2.5) Through Week 24
Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Secondary Outcome Measures
Average Absolute Change From Baseline in Sweat Chloride at Day 15 and Week 4
Sweat samples were collected using an approved collection device. Baseline was defined as the average of the measurements at screening and on Day 1 pre-dose. Change from Baseline in sweat chloride at Day 15 and Week 4 was calculated. The average of the 2 values (Change at Day 15 and Week 4) was reported.
Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
BMI was defined as weight in kg divided by height in square meter (m^2).
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants 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.
Absolute Change From Baseline in Lung Clearance Index 5.0 (LCI5.0) Through Week 24
LCI is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI5.0 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/20th of its starting value.
Absolute Change From Baseline in Sweat Chloride at Week 24
Sweat samples were collected using an approved collection device.
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Wang standards were used to calculate ppFEV1 (for age, gender, race, and height).
Relative Change From Baseline in ppFEV1 Through Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Wang standards were used to calculate ppFEV1 (for age, gender, race, and height).
Absolute Change From Baseline in BMI-for-age Z-score at Week 24
BMI was defined as weight in kg divided by height in m^2. z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score (BMI z-score). The BMI-for-age z-scores were calculated using National Center for Health Statistics growth charts.
Absolute Change From Baseline in Weight at Week 24
Absolute Change From Baseline in Weight-for-age Z-score at Week 24
Z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard. Weight, adjusted for age and sex, was analyzed as weight-for-age z-score (weight z-score). The weight-for-age z-scores were calculated using National Center for Health Statistics growth charts.
Absolute Change From Baseline in Height at Week 24
Absolute Change From Baseline in Height-for-age Z-score at Week 24
Z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard. Height, adjusted for age and sex, was analyzed as height-for-age z-score (height z-score). The height-for-age z-scores were calculated using National Center for Health Statistics growth charts.
Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains Through Week 24
The TSQM is a 14-item self-administered questionnaire which measures participants' experiences with their medication on four dimensions: effectiveness, side effects, convenience and global satisfaction. For each dimension, responses are added and transformed to a scale from 0 to 100, where higher scores indicate greater satisfaction.
Number of Pulmonary Exacerbation Events
Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. The number of events were reported.
Percentage of Participants With At Least 1 Pulmonary Exacerbation Event
Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Time-to-first Pulmonary Exacerbation
Time-to-first pulmonary exacerbation was analyzed using the Kaplan-Meier estimates. Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Any AE that increased in severity or newly developed at or after initial dosing of study drug to Week 28 was considered treatment-emergent.
Average Pre-dose Concentration (Ctrough,Ave) and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Ave) For Lumacaftor and Ivacaftor
Ctrough,ave is average of individual pre-dose observed concentrations across Week 4 and 24. C3-6h,ave is average of individual 3 to 6 hours post-dose observed concentrations across Day 1, 15 and Week 4. This outcome was not planned to be assessed in Placebo arm.
Full Information
NCT ID
NCT02514473
First Posted
July 23, 2015
Last Updated
September 19, 2017
Sponsor
Vertex Pharmaceuticals Incorporated
1. Study Identification
Unique Protocol Identification Number
NCT02514473
Brief Title
A Study to Evaluate the Efficacy and Safety of Lumacaftor in Combination With Ivacaftor in Subjects With CF, Homozygous for the F508del-CFTR Mutation
Official Title
A Phase 3, Double Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Lumacaftor in Combination With Ivacaftor in Subjects Aged 6 Through 11 Years With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
July 2015 (undefined)
Primary Completion Date
September 2016 (Actual)
Study Completion Date
September 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To evaluate the efficacy and safety of lumacaftor in combination with ivacaftor in subjects aged 6 Through 11 years with cystic fibrosis (CF), homozygous for the F508del CF transmembrane conductance regulator (CFTR) mutation
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
206 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LUM/IVA
Arm Type
Experimental
Arm Description
Fixed-dose combination with lumacaftor (LUM) 200 mg every 12 hours (q12h)/ ivacaftor (IVA) 250 mg q12h
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo q12h
Intervention Type
Drug
Intervention Name(s)
VX-809
Other Intervention Name(s)
lumacaftor
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Type
Drug
Intervention Name(s)
VX-770
Other Intervention Name(s)
ivacaftor
Primary Outcome Measure Information:
Title
Absolute Change From Baseline in Lung Clearance Index 2.5 (LCI2.5) Through Week 24
Description
Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Time Frame
Baseline, Through Week 24
Secondary Outcome Measure Information:
Title
Average Absolute Change From Baseline in Sweat Chloride at Day 15 and Week 4
Description
Sweat samples were collected using an approved collection device. Baseline was defined as the average of the measurements at screening and on Day 1 pre-dose. Change from Baseline in sweat chloride at Day 15 and Week 4 was calculated. The average of the 2 values (Change at Day 15 and Week 4) was reported.
Time Frame
Baseline, Day 15 and Week 4
Title
Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
Description
BMI was defined as weight in kg divided by height in square meter (m^2).
Time Frame
Baseline, Week 24
Title
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24
Description
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants 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.
Time Frame
Baseline, Through Week 24
Title
Absolute Change From Baseline in Lung Clearance Index 5.0 (LCI5.0) Through Week 24
Description
LCI is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI5.0 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/20th of its starting value.
Time Frame
Baseline, Through Week 24
Title
Absolute Change From Baseline in Sweat Chloride at Week 24
Description
Sweat samples were collected using an approved collection device.
Time Frame
Baseline, Week 24
Title
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Wang standards were used to calculate ppFEV1 (for age, gender, race, and height).
Time Frame
Baseline, Through Week 24
Title
Relative Change From Baseline in ppFEV1 Through Week 24
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Wang standards were used to calculate ppFEV1 (for age, gender, race, and height).
Time Frame
Baseline, Through Week 24
Title
Absolute Change From Baseline in BMI-for-age Z-score at Week 24
Description
BMI was defined as weight in kg divided by height in m^2. z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score (BMI z-score). The BMI-for-age z-scores were calculated using National Center for Health Statistics growth charts.
Time Frame
Baseline, Week 24
Title
Absolute Change From Baseline in Weight at Week 24
Time Frame
Baseline, Week 24
Title
Absolute Change From Baseline in Weight-for-age Z-score at Week 24
Description
Z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard. Weight, adjusted for age and sex, was analyzed as weight-for-age z-score (weight z-score). The weight-for-age z-scores were calculated using National Center for Health Statistics growth charts.
Time Frame
Baseline, Week 24
Title
Absolute Change From Baseline in Height at Week 24
Time Frame
Baseline, Week 24
Title
Absolute Change From Baseline in Height-for-age Z-score at Week 24
Description
Z-score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard. Height, adjusted for age and sex, was analyzed as height-for-age z-score (height z-score). The height-for-age z-scores were calculated using National Center for Health Statistics growth charts.
Time Frame
Baseline, Week 24
Title
Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains Through Week 24
Description
The TSQM is a 14-item self-administered questionnaire which measures participants' experiences with their medication on four dimensions: effectiveness, side effects, convenience and global satisfaction. For each dimension, responses are added and transformed to a scale from 0 to 100, where higher scores indicate greater satisfaction.
Time Frame
Baseline, Through Week 24
Title
Number of Pulmonary Exacerbation Events
Description
Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. The number of events were reported.
Time Frame
Baseline through Week 24
Title
Percentage of Participants With At Least 1 Pulmonary Exacerbation Event
Description
Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Time Frame
Baseline through Week 24
Title
Time-to-first Pulmonary Exacerbation
Description
Time-to-first pulmonary exacerbation was analyzed using the Kaplan-Meier estimates. Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Time Frame
Baseline through Week 24
Title
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Any AE that increased in severity or newly developed at or after initial dosing of study drug to Week 28 was considered treatment-emergent.
Time Frame
Baseline up to Week 28
Title
Average Pre-dose Concentration (Ctrough,Ave) and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Ave) For Lumacaftor and Ivacaftor
Description
Ctrough,ave is average of individual pre-dose observed concentrations across Week 4 and 24. C3-6h,ave is average of individual 3 to 6 hours post-dose observed concentrations across Day 1, 15 and Week 4. This outcome was not planned to be assessed in Placebo arm.
Time Frame
For Ctrough,ave: before morning dose on Week 4 and 24; For C3-6h,ave: 3 to 6 hours after morning dose on Day 1, 15 and Week 4
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
11 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects who weigh ≥15 kg without shoes a the Screening Visit
Subjects with confirmed diagnosis of CF at the Screening Visit.
Subjects who are homozygous for the F508del CFTR mutation
Subjects with ppFEV1 of ≥70 percentage points adjusted for age, sex, and height
Subjects with a screening LCI2.5 result greater than or equal to 7.5
Exclusion Criteria:
History of any comorbidity reviewed at the Screening Visit that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject.
Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject
Clinically significant abnormalities in hemoglobin, liver function, or renal function at the Screening Visit.
An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before Day 1
History of solid organ or hematological transplantation at the Screening Visit
Facility Information:
City
Birmingham
State/Province
Alabama
Country
United States
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Los Angeles
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California
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United States
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Palo Alto
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California
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Aurora
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Colorado
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Wilmington
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Delaware
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Orlando
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Atlanta
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Boston
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Omaha
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Manchester
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Chapel Hill
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North Carolina
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Cincinnati
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Ohio
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Cleveland
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Dayton
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Ohio
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Philadelphia
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Pennsylvania
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United States
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Pittsburgh
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Pennsylvania
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Charleston
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South Carolina
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Salt Lake City
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Utah
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Colchester
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Vermont
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Charlottesville
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Virginia
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Norfolk
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Virginia
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Richmond
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Seattle
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Washington
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Madison
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Wisconsin
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Milwaukee
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Wisconsin
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Herston
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Australia
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New South Wales
Country
Australia
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Parkville
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Australia
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Subiaco
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Australia
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Westmead
Country
Australia
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Brussels
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Belgium
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Leuven
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Belgium
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Vancouver
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British Columbia
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Canada
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Toronto
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Ontario
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Montreal
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Quebec
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Copenhagen
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Denmark
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Bordeaux
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France
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Bron
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France
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Paris Cedex 15
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France
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Paris
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France
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Berlin
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Germany
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Giessen
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Germany
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Hannover
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Germany
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Koeln
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Germany
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Munich
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Germany
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Stockholm
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Sweden
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Edinburgh
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Lothian Region
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United Kingdom
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Leeds
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West Yorkshire
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United Kingdom
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Belfast
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United Kingdom
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London
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
33331662
Citation
Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
Results Reference
derived
PubMed Identifier
28606620
Citation
Ratjen F, Hug C, Marigowda G, Tian S, Huang X, Stanojevic S, Milla CE, Robinson PD, Waltz D, Davies JC; VX14-809-109 investigator group. Efficacy and safety of lumacaftor and ivacaftor in patients aged 6-11 years with cystic fibrosis homozygous for F508del-CFTR: a randomised, placebo-controlled phase 3 trial. Lancet Respir Med. 2017 Jul;5(7):557-567. doi: 10.1016/S2213-2600(17)30215-1. Epub 2017 Jun 9. Erratum In: Lancet Respir Med. 2017 Aug;5(8):e28.
Results Reference
derived
Learn more about this trial
A Study to Evaluate the Efficacy and Safety of Lumacaftor in Combination With Ivacaftor in Subjects With CF, Homozygous for the F508del-CFTR Mutation
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