- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02514473
A Study to Evaluate the Efficacy and Safety of Lumacaftor in Combination With Ivacaftor in Subjects With CF, Homozygous for the F508del-CFTR Mutation
September 19, 2017 updated by: Vertex Pharmaceuticals Incorporated
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
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
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
206
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Herston, Australia
-
New South Wales, Australia
-
Parkville, Australia
-
Subiaco, Australia
-
Westmead, Australia
-
-
-
-
-
Brussels, Belgium
-
Leuven, Belgium
-
-
-
-
British Columbia
-
Vancouver, British Columbia, Canada
-
-
Ontario
-
Toronto, Ontario, Canada
-
-
Quebec
-
Montreal, Quebec, Canada
-
-
-
-
-
Copenhagen, Denmark
-
-
-
-
-
Bordeaux, France
-
Bron, France
-
Paris, France
-
Paris Cedex 15, France
-
-
-
-
-
Berlin, Germany
-
Giessen, Germany
-
Hannover, Germany
-
Koeln, Germany
-
Munich, Germany
-
-
-
-
-
Stockholm, Sweden
-
-
-
-
-
Belfast, United Kingdom
-
London, United Kingdom
-
-
Lothian Region
-
Edinburgh, Lothian Region, United Kingdom
-
-
West Yorkshire
-
Leeds, West Yorkshire, United Kingdom
-
-
-
-
Alabama
-
Birmingham, Alabama, United States
-
-
California
-
Los Angeles, California, United States
-
Palo Alto, California, United States
-
-
Colorado
-
Aurora, Colorado, United States
-
-
Delaware
-
Wilmington, Delaware, United States
-
-
Florida
-
Orlando, Florida, United States
-
-
Georgia
-
Atlanta, Georgia, United States
-
-
Illinois
-
Chicago, Illinois, United States
-
-
Iowa
-
Iowa City, Iowa, United States
-
-
Massachusetts
-
Boston, Massachusetts, United States
-
-
Minnesota
-
Minneapolis, Minnesota, United States
-
-
Missouri
-
Kansas City, Missouri, United States
-
-
Nebraska
-
Omaha, Nebraska, United States
-
-
New Hampshire
-
Manchester, New Hampshire, United States
-
-
North Carolina
-
Chapel Hill, North Carolina, United States
-
-
Ohio
-
Cincinnati, Ohio, United States
-
Cleveland, Ohio, United States
-
Dayton, Ohio, United States
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States
-
Pittsburgh, Pennsylvania, United States
-
-
South Carolina
-
Charleston, South Carolina, United States
-
-
Utah
-
Salt Lake City, Utah, United States
-
-
Vermont
-
Colchester, Vermont, United States
-
-
Virginia
-
Charlottesville, Virginia, United States
-
Norfolk, Virginia, United States
-
Richmond, Virginia, United States
-
-
Washington
-
Seattle, Washington, United States
-
-
Wisconsin
-
Madison, Wisconsin, United States
-
Milwaukee, Wisconsin, United States
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
6 years to 11 years (CHILD)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: LUM/IVA
Fixed-dose combination with lumacaftor (LUM) 200 mg every 12 hours (q12h)/ ivacaftor (IVA) 250 mg q12h
|
Other Names:
Other Names:
|
PLACEBO_COMPARATOR: Placebo
Matching placebo q12h
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Absolute Change From Baseline in Lung Clearance Index 2.5 (LCI2.5) Through Week 24
Time Frame: Baseline, 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.
|
Baseline, Through Week 24
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Absolute Change From Baseline in Weight at Week 24
Time Frame: Baseline, Week 24
|
Baseline, Week 24
|
|
Average Absolute Change From Baseline in Sweat Chloride at Day 15 and Week 4
Time Frame: Baseline, 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.
|
Baseline, Day 15 and Week 4
|
Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
Time Frame: Baseline, Week 24
|
BMI was defined as weight in kg divided by height in square meter (m^2).
|
Baseline, Week 24
|
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24
Time Frame: Baseline, 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.
|
Baseline, Through Week 24
|
Absolute Change From Baseline in Lung Clearance Index 5.0 (LCI5.0) Through Week 24
Time Frame: Baseline, 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.
|
Baseline, Through Week 24
|
Absolute Change From Baseline in Sweat Chloride at Week 24
Time Frame: Baseline, Week 24
|
Sweat samples were collected using an approved collection device.
|
Baseline, Week 24
|
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24
Time Frame: Baseline, 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).
|
Baseline, Through Week 24
|
Relative Change From Baseline in ppFEV1 Through Week 24
Time Frame: Baseline, 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).
|
Baseline, Through Week 24
|
Absolute Change From Baseline in BMI-for-age Z-score at Week 24
Time Frame: Baseline, 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.
|
Baseline, Week 24
|
Absolute Change From Baseline in Weight-for-age Z-score at Week 24
Time Frame: Baseline, 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.
|
Baseline, Week 24
|
Absolute Change From Baseline in Height at Week 24
Time Frame: Baseline, Week 24
|
Baseline, Week 24
|
|
Absolute Change From Baseline in Height-for-age Z-score at Week 24
Time Frame: Baseline, 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.
|
Baseline, Week 24
|
Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains Through Week 24
Time Frame: Baseline, 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.
|
Baseline, Through Week 24
|
Number of Pulmonary Exacerbation Events
Time Frame: Baseline through Week 24
|
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.
|
Baseline through Week 24
|
Percentage of Participants With At Least 1 Pulmonary Exacerbation Event
Time Frame: Baseline through Week 24
|
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.
|
Baseline through Week 24
|
Time-to-first Pulmonary Exacerbation
Time Frame: Baseline through Week 24
|
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.
|
Baseline through Week 24
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Baseline up to Week 28
|
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.
|
Baseline up to Week 28
|
Average Pre-dose Concentration (Ctrough,Ave) and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Ave) For Lumacaftor and Ivacaftor
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
|
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.
|
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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
July 1, 2015
Primary Completion (ACTUAL)
September 1, 2016
Study Completion (ACTUAL)
September 1, 2016
Study Registration Dates
First Submitted
July 23, 2015
First Submitted That Met QC Criteria
July 31, 2015
First Posted (ESTIMATE)
August 3, 2015
Study Record Updates
Last Update Posted (ACTUAL)
October 23, 2017
Last Update Submitted That Met QC Criteria
September 19, 2017
Last Verified
September 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- VX14-809-109
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cystic Fibrosis
-
Hospital de Clinicas de Porto AlegreUnknownCystic Fibrosis | Cystic Fibrosis Pulmonary Exacerbation | Cystic Fibrosis in Children | Cystic Fibrosis With ExacerbationBrazil
-
University of Colorado, DenverCystic Fibrosis FoundationTerminatedCystic Fibrosis-related Diabetes | Cystic Fibrosis Pulmonary Exacerbation | Cystic Fibrosis in ChildrenUnited States
-
Royal College of Surgeons, IrelandThe Hospital for Sick Children; Imperial College London; Erasmus Medical Center; University College Dublin and other collaboratorsActive, not recruitingCystic Fibrosis | Adherence, Medication | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis in Children | Cystic Fibrosis Liver DiseaseUnited Kingdom, Ireland
-
Herlev and Gentofte HospitalCopenhagen University Hospital, DenmarkActive, not recruitingMyocardial Infarction | Heart Diseases | Heart Failure | Stroke | Cystic Fibrosis | Heart Failure, Diastolic | Heart Failure, Systolic | Left Ventricular Dysfunction | Cystic Fibrosis-related Diabetes | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis of Pancreas | Cystic Fibrosis, Pulmonary | Cystic...Denmark
-
The Hospital for Sick ChildrenCanadian Cystic Fibrosis FoundationActive, not recruitingCystic Fibrosis | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis in ChildrenCanada
-
Arrowhead PharmaceuticalsTerminatedCystic Fibrosis, PulmonaryAustralia, New Zealand
-
AzurRx SASCompletedCystic Fibrosis | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis of PancreasTurkey, Hungary
-
Dartmouth-Hitchcock Medical CenterTrustees of Dartmouth CollegeWithdrawnCystic Fibrosis-related Diabetes | Cystic Fibrosis Liver Disease | CF - Cystic FibrosisUnited States
-
University Hospital, BordeauxCompleted
-
University of PortsmouthUniversity Hospital Southampton NHS Foundation Trust; Loughborough University; Queen Alexandra HospitalTerminated
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States