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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02514473




Registration number
NCT02514473
Ethics application status
Date submitted
23/07/2015
Date registered
3/08/2015
Date last updated
23/10/2017

Titles & IDs
Public 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
Scientific 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
Secondary ID [1] 0 0
VX14-809-109
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - VX-809
Treatment: Drugs - Placebo
Treatment: Drugs - VX-770

Experimental: LUM/IVA - Fixed-dose combination with lumacaftor (LUM) 200 mg every 12 hours (q12h)/ ivacaftor (IVA) 250 mg q12h

Placebo Comparator: Placebo - Matching placebo q12h


Treatment: Drugs: VX-809


Treatment: Drugs: Placebo


Treatment: Drugs: VX-770


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline, Through Week 24
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline, Day 15 and Week 4
Secondary outcome [2] 0 0
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).
Timepoint [2] 0 0
Baseline, Week 24
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Baseline, Through Week 24
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Baseline, Through Week 24
Secondary outcome [5] 0 0
Absolute Change From Baseline in Sweat Chloride at Week 24 - Sweat samples were collected using an approved collection device.
Timepoint [5] 0 0
Baseline, Week 24
Secondary outcome [6] 0 0
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).
Timepoint [6] 0 0
Baseline, Through Week 24
Secondary outcome [7] 0 0
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).
Timepoint [7] 0 0
Baseline, Through Week 24
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Baseline, Week 24
Secondary outcome [9] 0 0
Absolute Change From Baseline in Weight at Week 24
Timepoint [9] 0 0
Baseline, Week 24
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
Baseline, Week 24
Secondary outcome [11] 0 0
Absolute Change From Baseline in Height at Week 24
Timepoint [11] 0 0
Baseline, Week 24
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
Baseline, Week 24
Secondary outcome [13] 0 0
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.
Timepoint [13] 0 0
Baseline, Through Week 24
Secondary outcome [14] 0 0
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.
Timepoint [14] 0 0
Baseline through Week 24
Secondary outcome [15] 0 0
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.
Timepoint [15] 0 0
Baseline through Week 24
Secondary outcome [16] 0 0
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.
Timepoint [16] 0 0
Baseline through Week 24
Secondary outcome [17] 0 0
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.
Timepoint [17] 0 0
Baseline up to Week 28
Secondary outcome [18] 0 0
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.
Timepoint [18] 0 0
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

Eligibility
Key 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
Minimum age
6 Years
Maximum age
11 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Herston
Recruitment hospital [2] 0 0
- New South Wales
Recruitment hospital [3] 0 0
- Parkville
Recruitment hospital [4] 0 0
- Subiaco
Recruitment hospital [5] 0 0
- Westmead
Recruitment postcode(s) [1] 0 0
- Herston
Recruitment postcode(s) [2] 0 0
- New South Wales
Recruitment postcode(s) [3] 0 0
- Parkville
Recruitment postcode(s) [4] 0 0
- Subiaco
Recruitment postcode(s) [5] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Delaware
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Iowa
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
Nebraska
Country [13] 0 0
United States of America
State/province [13] 0 0
New Hampshire
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
South Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Utah
Country [19] 0 0
United States of America
State/province [19] 0 0
Vermont
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
United States of America
State/province [21] 0 0
Washington
Country [22] 0 0
United States of America
State/province [22] 0 0
Wisconsin
Country [23] 0 0
Belgium
State/province [23] 0 0
Brussels
Country [24] 0 0
Belgium
State/province [24] 0 0
Leuven
Country [25] 0 0
Canada
State/province [25] 0 0
British Columbia
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
Canada
State/province [27] 0 0
Quebec
Country [28] 0 0
Denmark
State/province [28] 0 0
Copenhagen
Country [29] 0 0
France
State/province [29] 0 0
Bordeaux
Country [30] 0 0
France
State/province [30] 0 0
Bron
Country [31] 0 0
France
State/province [31] 0 0
Paris Cedex 15
Country [32] 0 0
France
State/province [32] 0 0
Paris
Country [33] 0 0
Germany
State/province [33] 0 0
Berlin
Country [34] 0 0
Germany
State/province [34] 0 0
Giessen
Country [35] 0 0
Germany
State/province [35] 0 0
Hannover
Country [36] 0 0
Germany
State/province [36] 0 0
Koeln
Country [37] 0 0
Germany
State/province [37] 0 0
Munich
Country [38] 0 0
Sweden
State/province [38] 0 0
Stockholm
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Lothian Region
Country [40] 0 0
United Kingdom
State/province [40] 0 0
West Yorkshire
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Belfast
Country [42] 0 0
United Kingdom
State/province [42] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Vertex Pharmaceuticals Incorporated
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/show/NCT02514473
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications