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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02544451
Ethics application status
Date submitted
1/09/2015
Date registered
9/09/2015
Date last updated
24/05/2021

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
Treatment: Drugs - LUM/IVA

Experimental: Treatment Period 1: LUM/IVA to LUM/IVA -

Experimental: Treatment Period 1: Placebo (PBO) to LUM/IVA -

No intervention: Treatment Period 1: Observational Cohort -

Experimental: Treatment Period 2: LUM/IVA -


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).

Treatment: Drugs: LUM/IVA
LUM 200 mg q12h/IVA 250 mg q12h (for 6 through 11 years of age).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Treatment Period 1 (Treatment Cohorts): 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
Timepoint [1] 0 0
From Parent Study Baseline at Week 96
Secondary outcome [2] 0 0
Absolute Change in Sweat Chloride
Timepoint [2] 0 0
From Parent Study Baseline at Week 96
Secondary outcome [3] 0 0
Absolute Change in Body Mass Index (BMI)
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
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
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)
Timepoint [7] 0 0
From Parent Study Baseline at Week 96
Secondary outcome [8] 0 0
Relative Change in ppFEV1
Timepoint [8] 0 0
From Parent Study Baseline at Week 96
Secondary outcome [9] 0 0
Absolute Change in BMI-for-age Z-score
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
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
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
Timepoint [14] 0 0
From Parent Study Baseline at Week 96
Secondary outcome [15] 0 0
Time-to-first Pulmonary Exacerbation
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
Timepoint [16] 0 0
From Parent Study Baseline through Week 96
Secondary outcome [17] 0 0
Number of Pulmonary Exacerbation Events Per Patient-year
Timepoint [17] 0 0
From Parent Study Baseline through Week 96
Secondary outcome [18] 0 0
Rate of Change in LCI 2.5
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
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
Timepoint [20] 0 0
Day 15 after first dose of LUM/IVA through Week 96
Secondary outcome [21] 0 0
Treatment Period 2: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [21] 0 0
Day 1 up to Week 168

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
Sex
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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2020
Sample size
Target
Accrual to date
Final
246
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
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United States of America
State/province [2] 0 0
Arizona
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California
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Colorado
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Delaware
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Florida
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Georgia
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Illinois
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Indiana
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Iowa
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Massachusetts
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Minnesota
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Missouri
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Nebraska
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New Hampshire
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New York
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North Carolina
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Ohio
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Oregon
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South Carolina
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Utah
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Washington
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Wisconsin
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Belgium
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Brussels
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Leuven
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British Columbia
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Ontario
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Quebec
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Denmark
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Copenhagen
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France
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Cedex
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France
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Bordeaux Cedex
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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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Germany
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Berlin
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Germany
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Giessen
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Germany
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Hanover
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Germany
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Koeln
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Sweden
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Stockholm
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United Kingdom
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West Yorkshire
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United Kingdom
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Belfast
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Edinburgh
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United Kingdom
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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/study/NCT02544451
Trial related presentations / publications
Chilvers MA, Davies JC, Milla C, Tian S, Han Z, Cornell AG, Owen CA, Ratjen F. Long-term safety and efficacy of lumacaftor-ivacaftor therapy in children aged 6-11 years with cystic fibrosis homozygous for the F508del-CFTR mutation: a phase 3, open-label, extension study. Lancet Respir Med. 2021 Jul;9(7):721-732. doi: 10.1016/S2213-2600(20)30517-8. Epub 2021 Jan 28. Erratum In: Lancet Respir Med. 2021 Apr;9(4):e38. doi: 10.1016/S2213-2600(21)00093-X.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02544451