- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01807923
A Study of Lumacaftor in Combination With Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Who Are Homozygous for the F508del-CFTR Mutation (TRAFFIC)
A Phase 3, Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Lumacaftor in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation
Study Overview
Status
Intervention / Treatment
Detailed Description
This was a Phase 3, randomized, double-blind, placebo-controlled, parallel-group multicenter study of orally administered lumacaftor in combination with ivacaftor in participants aged 12 years and older with CF who are homozygous for the F508del-CFTR mutation.
The study included a Screening Period (Day -28 through Day -1), a Treatment Period (Day 1 [first dose of study drug] to Week 24 ± 5 days), and a Safety Follow-up Visit (4 weeks ± 7 days after the Week 24 Visit).
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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New South Wales
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Broadmeadow, New South Wales, Australia
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Westmead, New South Wales, Australia
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South Australia
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Adelaide, South Australia, Australia
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British Columbia
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Halifax, British Columbia, Canada
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Vancouver, British Columbia, Canada
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Ontario
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Ottawa, Ontario, Canada
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Toronto, Ontario, Canada
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Brno, Czech Republic
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Plzen-Bory, Czech Republic
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Praha 5, Czech Republic
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Bas Rhin
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Strasbourg Cedex 2, Bas Rhin, France
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Finistere
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Roscoff, Finistere, France
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Paris
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Paris Cedex 14, Paris, France
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Paris Cedex 15, Paris, France
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Rhone
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Bron Cedex, Rhone, France
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Pierre Benite, Rhone, France
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Berlin, Germany
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Baden Wuerttemberg
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Tuebingen, Baden Wuerttemberg, Germany
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Bayern
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Erlangen, Bayern, Germany
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Wuerzburg, Bayern, Germany
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Nordrhein Westfalen
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Koeln, Nordrhein Westfalen, Germany
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Sachsen
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Leipzig, Sachsen, Germany
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Dublin, Ireland
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Dublin
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Tallaght, Dublin, Ireland
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Ancona, Italy
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Firenze, Italy
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Genova, Italy
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Milano, Italy
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Roma, Italy
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Verona, Italy
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Amsterdam, Netherlands
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Den Haag, Netherlands
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Nijmegen, Netherlands
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Rotterdam, Netherlands
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Goteborg, Sweden
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Stockholm, Sweden
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Uppsala, Sweden
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Belfast, United Kingdom
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Devon
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Exeter, Devon, United Kingdom
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Hampshire
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Southhampton, Hampshire, United Kingdom
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Nottinghamshire
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Nottingham, Nottinghamshire, United Kingdom
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West Midlands
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Birmingham, West Midlands, United Kingdom
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Alabama
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Birmingham, Alabama, United States
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Alaska
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Anchorage, Alaska, United States
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Arizona
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Tucson, Arizona, United States
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Arkansas
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Little Rock, Arkansas, United States
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California
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Fresno, California, United States
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La Jolla, California, United States
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Loma Linda, California, United States
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Long Beach, California, United States
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Los Angeles, California, United States
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Madera, California, United States
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Oakland, California, United States
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Palo Alto, California, United States
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Colorado
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Denver, Colorado, United States
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Florida
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Gainsville, Florida, United States
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Hollywood, Florida, United States
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Orlando, Florida, United States
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Tampa, Florida, United States
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Georgia
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Atlanta, Georgia, United States
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Idaho
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Boise, Idaho, United States
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Illinois
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Chicago, Illinois, United States
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Park Ridge, Illinois, United States
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Peoria, Illinois, United States
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Maryland
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Baltimore, Maryland, United States
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Massachusetts
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Boston, Massachusetts, United States
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Michigan
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Ann Arbor, Michigan, United States
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Missouri
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Kansas City, Missouri, United States
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New Hampshire
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Bedford, New Hampshire, United States
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Lebanon, New Hampshire, United States
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New Jersey
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Long Branch, New Jersey, United States
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New York
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Hawthorne, New York, United States
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New York, New York, United States
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Valhalla, New York, United States
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North Carolina
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Chapel Hill, North Carolina, United States
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Durham, North Carolina, United States
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Ohio
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Akron, Ohio, United States
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Cincinnati, Ohio, United States
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Dayton, Ohio, United States
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Oregon
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Portland, Oregon, United States
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Pennsylvania
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Hershey, Pennsylvania, United States
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Tennessee
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Knoxville, Tennessee, United States
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Texas
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Austin, Texas, United States
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Tyler, Texas, United States
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Vermont
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Colchester, Vermont, United States
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Virginia
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Charlottesville, Virginia, United States
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Norfolk, Virginia, United States
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Washington
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Seattle, Washington, United States
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West Virginia
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Morgantown, West Virginia, United States
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Wisconsin
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Madison, Wisconsin, United States
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Confirmed diagnosis of CF
- Homozygous for the F508del CFTR mutation
- Forced expiratory volume in 1 second (FEV1) greater than or equal to (>=) 40 percent (%) and less than or equal to (=<) 90% of predicted normal for age, sex, and height
- Willing to remain on a stable CF medication regimen through Week 24 or, if applicable, the Safety Follow up Visit
Exclusion Criteria:
- An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before first dose of study drug
- History of solid organ or hematological transplantation
- History of alcohol or drug abuse in the past year
- Ongoing or prior participation in an investigational drug study (including studies investigating lumacaftor and/or ivacaftor) within 30 days of screening
- Use of strong inhibitors, moderate inducers or strong inducers of Cytochrome P450 3A (CYP3A) within 14 days before Day 1 of dosing
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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PLACEBO_COMPARATOR: Placebo
Placebo matched to lumacaftor (LUM, VX-809) and ivacaftor (IVA, VX-770) tablet every 12 hours (q12h), up to Week 24.
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Matching placebo tablet
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EXPERIMENTAL: LUM 600 mg qd/IVA 250 mg q12h
LUM 600 milligram (mg) plus IVA 250 mg fixed-dose combination (FDC) tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
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Fixed dose combination tablet
Other Names:
Film-coated tablet
Other Names:
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EXPERIMENTAL: LUM 400 mg q12h/ IVA 250 mg q12h
LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
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Fixed dose combination tablet
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 24
Time Frame: Baseline, Week 16 and 24
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Absolute change from baseline at Week 24 was assessed as the average treatment effect at Week 16 and at Week 24.
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, race, and height).
The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older.
The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years.
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Baseline, Week 16 and 24
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Relative Change From Baseline in Percent Predicted FEV1 at Week 24
Time Frame: Baseline, Week 16 and 24
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Assessed as the average treatment effect at Week 16 and at Week 24.
FEV1 and percent predicted FEV1 are defined in Outcome Measure (OM) 1.
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Baseline, Week 16 and 24
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Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
Time Frame: Baseline, Week 24
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BMI was defined as weight in kilogram (kg) divided by height*height in square meter (m^2).
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Baseline, Week 24
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Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24
Time Frame: Baseline, Week 24
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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), the scaled score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
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Baseline, Week 24
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Percentage of Participants With Response Based on Percent Predicted FEV1
Time Frame: Week 16 and 24
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A participant was considered as a responder if the participant had >=5% increase from baseline in average percent predicted FEV1 at Week 16 and at Week 24 (relative change).
FEV1 and percent predicted FEV1 are defined in OM 1.
A participant with a missing average relative change from baseline in percent predicted FEV1 at Week 16 and at Week 24 was considered as a non-responder.
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Week 16 and 24
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Number of Pulmonary Exacerbation Events
Time Frame: through Week 24
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The total number of days on study is equal to the Week 24 date or the last dose date (whichever occurred last) minus the first dose date plus 1.
The total number of years (48 weeks) on study is equal to the number of days on study divided by 336.
Pulmonary exacerbation events per year (48 weeks) are reported.
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through Week 24
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Absolute Change From Baseline in Weight at Week 24
Time Frame: Baseline, Week 24
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Baseline, Week 24
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Percentage of Participants With At Least 1 Pulmonary Exacerbation Event
Time Frame: through Week 24
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through Week 24
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Absolute Change From Baseline in Euro Quality of Life Scale (EuroQol) 5-Dimension-3 Level (EQ-5D-3L) Index Score at Week 24
Time Frame: Baseline, Week 24
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EQ-5D-3L: participant rated questionnaire to assess health-related quality of life.
It consists of EQ-5D descriptive system and EQ-5D Visual Analog Scale (VAS).
EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression.
Each dimension has 3 levels: no problems (1), some problems (2), and extreme problems (3).
The 5 dimensional 3-level systems are converted into a single index utility score.
Values for theoretically possible health states are calculated using a regression model and weighted according to the social preferences of the Unites States (US) general population.
For this population, the possible EQ-5D-3L index scores ranges from -0.11 (that is, 3 for all 5 dimensions) to 1.0 (that is, 1 for all 5 dimensions), where higher scores indicate a better health state.
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Baseline, Week 24
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Absolute Change From Baseline in EQ-5D-3L VAS Score at Week 24
Time Frame: Baseline, Week 24
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The EQ-5D-3L VAS records the participant's self-rated health on a vertical, visual analogue scale where the best state a participant can imagine is marked 100 and the worst state a participant can imagine is marked 0, higher scores indicates a better health state.
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Baseline, Week 24
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Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domain Scores at Week 24
Time Frame: Baseline, Week 24
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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.
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Baseline, Week 24
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Absolute Change From Baseline in BMI-for-age Z-score at Week 24
Time Frame: Baseline, Week 24
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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 and how unusual the measurement is with range from -infinity to + infinity; 0: same mean, >0: a greater mean, and <0: a lesser mean than the standard.
BMI-for-age z-score was calculated by using Centers for Disease Control and Prevention (CDC) growth charts for the pediatric population.
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Baseline, Week 24
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Time-to-First Pulmonary Exacerbation
Time Frame: through Week 24
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Time to first pulmonary exacerbation was assessed using Cox Regression.
For participants who completed 24 weeks of treatment, participants without a pulmonary exacerbation before treatment completion were considered censored at the time of treatment completion or at the Week 24 Visit (whichever occurred last).
For participants who prematurely discontinued study treatment, participants without a pulmonary exacerbation through the Week 24 Visit were considered censored at the time of the Week 24 Visit.
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through Week 24
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Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Treatment-Emergent Adverse Events (SAEs)
Time Frame: up to Week 28
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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 Nonserious 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, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event.
Any AE that increased in severity or that was newly developed at or after the initial dosing of study drug to 28 days after the last dose of study drug is considered treatment-emergent.
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up to Week 28
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Pre-dose Concentration (Ctrough), Average Pre-dose Concentration (Ctrough,Avg), 3 to 6 Hours Post-dose Concentration (C3-6h), and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Avg)
Time Frame: For C3-6h: 3 to 6 hours after morning dose on Day 1 and 15, Week 4 and 8; For C3-6h,avg 3 to 6 hours after morning dose on Day 15, Week 4 and 8; For Ctrough and Ctrough,avg: before morning dose on Week 4, 8, and 16
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Ctrough, Ctrough, avg, C3-6h, and C3-6h, avg for lumacaftor, M28 lumacaftor (lumacaftor metabolite), ivacaftor, M1 ivacaftor (ivacaftor metabolite), and M6 ivacaftor (ivacaftor metabolite) were calculated.
C3-6h,ave is average of individual 3 to 6 hours post-dose observed concentrations across Day 15, and Weeks 4 and 8 and Ctrough, ave is average of individual pre-dose observed concentrations across Weeks 4, 8, and 16.
This outcome was not planned to be assessed in Placebo arm.
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For C3-6h: 3 to 6 hours after morning dose on Day 1 and 15, Week 4 and 8; For C3-6h,avg 3 to 6 hours after morning dose on Day 15, Week 4 and 8; For Ctrough and Ctrough,avg: before morning dose on Week 4, 8, and 16
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Collaborators and Investigators
Publications and helpful links
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.
- Flume PA, Suthoff ED, Kosinski M, Marigowda G, Quittner AL. Measuring recovery in health-related quality of life during and after pulmonary exacerbations in patients with cystic fibrosis. J Cyst Fibros. 2019 Sep;18(5):737-742. doi: 10.1016/j.jcf.2018.12.004. Epub 2018 Dec 23.
- McColley SA, Konstan MW, Ramsey BW, Stuart Elborn J, Boyle MP, Wainwright CE, Waltz D, Vera-Llonch M, Marigowda G, Jiang JG, Rubin JL. Lumacaftor/Ivacaftor reduces pulmonary exacerbations in patients irrespective of initial changes in FEV1. J Cyst Fibros. 2019 Jan;18(1):94-101. doi: 10.1016/j.jcf.2018.07.011. Epub 2018 Aug 23.
- Elborn JS, Ramsey BW, Boyle MP, Konstan MW, Huang X, Marigowda G, Waltz D, Wainwright CE; VX-809 TRAFFIC and TRANSPORT study groups. Efficacy and safety of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis homozygous for Phe508del CFTR by pulmonary function subgroup: a pooled analysis. Lancet Respir Med. 2016 Aug;4(8):617-626. doi: 10.1016/S2213-2600(16)30121-7. Epub 2016 Jun 10.
- Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, Colombo C, Davies JC, De Boeck K, Flume PA, Konstan MW, McColley SA, McCoy K, McKone EF, Munck A, Ratjen F, Rowe SM, Waltz D, Boyle MP; TRAFFIC Study Group; TRANSPORT Study Group. Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR. N Engl J Med. 2015 Jul 16;373(3):220-31. doi: 10.1056/NEJMoa1409547. Epub 2015 May 17.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- VX12-809-103
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.
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