Clinical trial NCT02544451: Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Lumacaftor in Combination With Ivacaftor
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2015-09-09
Enrollment: 246
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

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).

Primary outcomes:
measure: 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)
timeFrame: Day 1 up to Week 100
Secondary outcomes:
measure: Absolute Change in Lung Clearance Index (LCI) 2.5
timeFrame: From Parent Study Baseline at Week 96
measure: Absolute Change in Sweat Chloride
timeFrame: From Parent Study Baseline at Week 96
measure: Absolute Change in Body Mass Index (BMI)
timeFrame: From Parent Study Baseline at Week 96
measure: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
timeFrame: From Parent Study Baseline at Week 96
measure: Observational Cohort: Safety as Assessed by Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Week 100
measure: Absolute Change in LCI 5.0
timeFrame: From Parent Study Baseline at Week 96
measure: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
timeFrame: From Parent Study Baseline at Week 96
measure: Relative Change in ppFEV1
timeFrame: From Parent Study Baseline at Week 96
measure: Absolute Change in BMI-for-age Z-score
timeFrame: From Parent Study Baseline at Week 96
measure: Absolute Change in Weight
timeFrame: From Parent Study Baseline at Week 96
measure: Absolute Change in Weight-for-age Z-score
timeFrame: From Parent Study Baseline at Week 96
measure: Absolute Change in Height
timeFrame: From Parent Study Baseline at Week 96
measure: Absolute Change in Height-for-age Z-score
timeFrame: From Parent Study Baseline at Week 96
measure: Absolute Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Total Domain Score
timeFrame: From Parent Study Baseline at Week 96
measure: Time-to-first Pulmonary Exacerbation
timeFrame: From Parent Study Baseline through Week 96
measure: Percentage of Participants Having At Least 1 Pulmonary Exacerbation Event
timeFrame: From Parent Study Baseline through Week 96
measure: Number of Pulmonary Exacerbation Events Per Patient-year
timeFrame: From Parent Study Baseline through Week 96
measure: Rate of Change in LCI 2.5
timeFrame: Day 15 after first dose of LUM/IVA through Week 96
measure: Rate of Change in LCI 5.0
timeFrame: Day 15 after first dose of LUM/IVA through Week 96
measure: Rate of Change in ppFEV1
timeFrame: Day 15 after first dose of LUM/IVA through Week 96
measure: Treatment Period 2: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Week 168
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Tucson
country: United States
state: Arizona
city: Long Beach
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Wilmington
country: United States
state: Delaware
city: Jacksonville
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Iowa City
country: United States
state: Iowa
city: Boston
country: United States
state: Massachusetts
city: Minneapolis
country: United States
state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Lebanon
country: United States
state: New Hampshire
city: Buffalo
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Pittsburgh
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Austin
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Colchester
country: United States
state: Vermont
city: Charlottesville
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
city: Milwaukee
country: United States
state: Wisconsin
city: Parkville
country: Australia
state: Victoria
city: Herston
country: Australia
city: New Lambton Heights
country: Australia
city: Subiaco
country: Australia
city: Westmead
country: Australia
city: Brussels
country: Belgium
city: Leuven
country: Belgium
city: Vancouver
country: Canada
state: British Columbia
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Copenhagen
country: Denmark
city: Bron
country: France
state: Cedex
city: Bordeaux Cedex
country: France
city: Paris Cedex 15
country: France
city: Paris
country: France
city: Berlin
country: Germany
city: Giessen
country: Germany
city: Hanover
country: Germany
city: Koeln
country: Germany
city: Stockholm
country: Sweden
city: Leeds
country: United Kingdom
state: West Yorkshire
city: Belfast
country: United Kingdom
city: Edinburgh
country: United Kingdom
city: London
country: United Kingdom
Study officials:
References:
citation: 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.