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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02544451




Registration number
NCT02544451
Ethics application status
Date submitted
1/09/2015
Date registered
9/09/2015
Date last updated
29/10/2019

Titles & IDs
Public title
Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Lumacaftor in Combination With Ivacaftor
Scientific title
A Phase 3, Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Lumacaftor in Combination With Ivacaftor in Subjects Aged 6 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
Secondary ID [1] 0 0
VX15-809-110
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 - LUM/IVA

Experimental: LUM/IVA to LUM/IVA -

Experimental: Placebo (PBO) to LUM/IVA -

No Intervention: Observational Cohort -


Treatment: Drugs: LUM/IVA
Lumacaftor (LUM) 200 mg every 12 hours (q12h)/ivacaftor (IVA) 250 mg q12h (for 6 through 11 years of age).
LUM 400 mg q12h/IVA 250 mg q12h (for 12 years and older).

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

Outcomes
Primary outcome [1] 0 0
Treatment Cohort: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [1] 0 0
Day 1 up to Week 100
Secondary outcome [1] 0 0
Absolute Change in Lung Clearance Index (LCI) 2.5 - LCI 2.5 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
From Parent Study Baseline at Week 96
Secondary outcome [2] 0 0
Absolute Change in Sweat Chloride - Sweat samples were collected using an approved collection device.
Timepoint [2] 0 0
From Parent Study Baseline at Week 96
Secondary outcome [3] 0 0
Absolute Change in Body Mass Index (BMI) - BMI was defined as weight in kilograms divided by height in square meter (m^2).
Timepoint [3] 0 0
From Parent Study Baseline at Week 96
Secondary outcome [4] 0 0
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score - 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, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Timepoint [4] 0 0
From Parent Study Baseline at Week 96
Secondary outcome [5] 0 0
Observational Cohort: Safety as Assessed by Serious Adverse Events (SAEs)
Timepoint [5] 0 0
Day 1 up to Week 100
Secondary outcome [6] 0 0
Absolute Change in LCI 5.0 - LCI 5.0 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/20th of its starting value.
Timepoint [6] 0 0
From Parent Study Baseline at Week 96
Secondary outcome [7] 0 0
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) - FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Timepoint [7] 0 0
From Parent Study Baseline at Week 96
Secondary outcome [8] 0 0
Relative Change in ppFEV1 - FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Timepoint [8] 0 0
From Parent Study Baseline at Week 96
Secondary outcome [9] 0 0
Absolute Change in BMI-for-age Z-score - BMI was defined as weight in kilograms divided by height in m^2. z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Timepoint [9] 0 0
From Parent Study Baseline at Week 96
Secondary outcome [10] 0 0
Absolute Change in Weight
Timepoint [10] 0 0
From Parent Study Baseline at Week 96
Secondary outcome [11] 0 0
Absolute Change in Weight-for-age Z-score - z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Timepoint [11] 0 0
From Parent Study Baseline at Week 96
Secondary outcome [12] 0 0
Absolute Change in Height
Timepoint [12] 0 0
From Parent Study Baseline at Week 96
Secondary outcome [13] 0 0
Absolute Change in Height-for-age Z-score - z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Timepoint [13] 0 0
From Parent Study Baseline at Week 96
Secondary outcome [14] 0 0
Absolute Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Total Domain Score - The TSQM measures participants' experiences with their medication on four dimensions: effectiveness, side effects, convenience and global satisfaction. For each dimension, responses are added and transformed in the total domain score, which ranges from 0 to 100, where higher scores indicate greater satisfaction.
Timepoint [14] 0 0
From Parent Study Baseline at Week 96
Secondary outcome [15] 0 0
Time-to-first Pulmonary Exacerbation - 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
From Parent Study Baseline through Week 96
Secondary outcome [16] 0 0
Percentage of Participants Having 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 [16] 0 0
From Parent Study Baseline through Week 96
Secondary outcome [17] 0 0
Number of Pulmonary Exacerbation Events Per Patient-year - 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 [17] 0 0
From Parent Study Baseline through Week 96
Secondary outcome [18] 0 0
Rate of Change in LCI 2.5 - Rate of change analysis evaluates the change in LCI 2.5 after long term treatment with LUM/IVA. A rate of change equal to zero would indicate that treatment effects were stable.
Timepoint [18] 0 0
Day 15 after first dose of LUM/IVA through Week 96
Secondary outcome [19] 0 0
Rate of Change in LCI 5.0 - Rate of change analysis evaluates the change in LCI 5.0 after long term treatment with LUM/IVA. A rate of change equal to zero would indicate that treatment effects were stable.
Timepoint [19] 0 0
Day 15 after first dose of LUM/IVA through Week 96
Secondary outcome [20] 0 0
Rate of Change in ppFEV1 - Rate of change analysis evaluates the change in ppFEV1 after long term treatment with LUM/IVA. A rate of change equal to zero would indicate that treatment effects were stable.
Timepoint [20] 0 0
Day 15 after first dose of LUM/IVA through Week 96

Eligibility
Key inclusion criteria
Subjects entering the Treatment Cohort must meet both of the following criteria:

- Completed study visits up to Week 24 of Study 109 or Week 26 of Study 011B and did not
permanently discontinue treatment

- Willing to remain on a stable CF medication through the Safety Follow-up Visit.

Subjects entering the Observational Cohort must meet 1 of the following criteria:

- Completed 24 weeks of study drug treatment in Study 109 or completed 24 weeks of study
drug treatment and the Week 26 Safety Follow up in Study 011B.

- Received at least 4 weeks of study drug and completed visits up to Week 24 of Study
109 or Week 26 of Study 011B.
Minimum age
6 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria (Treatment Cohort Only):

- History of any comorbidity or laboratory abnormality 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 (e.g., cirrhosis with portal hypertension).

- Pregnant and nursing females.

- Sexually active subjects of reproductive potential who are not willing to follow the
contraception requirements.

- History of drug intolerance in the prior study that would pose an additional risk to
the subject in the opinion of investigator

- History of poor compliance with study drug and/or procedure in the previous study as
deemed by the investigator.

- Participation in an investigational drug trial (including studies investigating
lumacaftor and/or ivacaftor).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
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)
VIC
Recruitment hospital [1] 0 0
- Parkville
Recruitment hospital [2] 0 0
- Herston
Recruitment hospital [3] 0 0
- New Lambton Heights
Recruitment hospital [4] 0 0
- Subiaco
Recruitment hospital [5] 0 0
- Westmead
Recruitment postcode(s) [1] 0 0
- Parkville
Recruitment postcode(s) [2] 0 0
- Herston
Recruitment postcode(s) [3] 0 0
- New Lambton Heights
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
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Delaware
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Iowa
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Minnesota
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
Nebraska
Country [15] 0 0
United States of America
State/province [15] 0 0
New Hampshire
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
North Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Ohio
Country [19] 0 0
United States of America
State/province [19] 0 0
Oregon
Country [20] 0 0
United States of America
State/province [20] 0 0
Pennsylvania
Country [21] 0 0
United States of America
State/province [21] 0 0
South Carolina
Country [22] 0 0
United States of America
State/province [22] 0 0
Texas
Country [23] 0 0
United States of America
State/province [23] 0 0
Utah
Country [24] 0 0
United States of America
State/province [24] 0 0
Vermont
Country [25] 0 0
United States of America
State/province [25] 0 0
Virginia
Country [26] 0 0
United States of America
State/province [26] 0 0
Washington
Country [27] 0 0
United States of America
State/province [27] 0 0
Wisconsin
Country [28] 0 0
Belgium
State/province [28] 0 0
Brussels
Country [29] 0 0
Belgium
State/province [29] 0 0
Leuven
Country [30] 0 0
Canada
State/province [30] 0 0
British Columbia
Country [31] 0 0
Canada
State/province [31] 0 0
Ontario
Country [32] 0 0
Canada
State/province [32] 0 0
Quebec
Country [33] 0 0
Denmark
State/province [33] 0 0
Copenhagen
Country [34] 0 0
France
State/province [34] 0 0
Cedex
Country [35] 0 0
France
State/province [35] 0 0
Bordeaux Cedex
Country [36] 0 0
France
State/province [36] 0 0
Paris Cedex 15
Country [37] 0 0
France
State/province [37] 0 0
Paris
Country [38] 0 0
Germany
State/province [38] 0 0
Berlin
Country [39] 0 0
Germany
State/province [39] 0 0
Giessen
Country [40] 0 0
Germany
State/province [40] 0 0
Hanover
Country [41] 0 0
Germany
State/province [41] 0 0
Koeln
Country [42] 0 0
Sweden
State/province [42] 0 0
Stockholm
Country [43] 0 0
United Kingdom
State/province [43] 0 0
West Yorkshire
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Belfast
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Edinburgh
Country [46] 0 0
United Kingdom
State/province [46] 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
Study 110 is a Phase 3, multicenter study in subjects aged 6 years and older with cystic
fibrosis (CF) who are homozygous for the F508del-CF transmembrane conductance regulator
(CFTR) mutation and who participated in Study 109 (NCT02514473) or Study 011B (NCT01897233).
Study 110 is designed to evaluate the safety and efficacy of long term treatment of
lumacaftor in combination with ivacaftor.
Trial website
https://clinicaltrials.gov/show/NCT02544451
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