Clinical trial NCT02514473: A Study to Evaluate the Efficacy and Safety of Lumacaftor in Combination With Ivacaftor in Subjects With CF, Homozygous for the F508del-CFTR Mutation
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2015-08-03
Enrollment: 206
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

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

Primary outcomes:
measure: Absolute Change From Baseline in Lung Clearance Index 2.5 (LCI2.5) Through Week 24
timeFrame: Baseline, Through Week 24
Secondary outcomes:
measure: Average Absolute Change From Baseline in Sweat Chloride at Day 15 and Week 4
timeFrame: Baseline, Day 15 and Week 4
measure: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
timeFrame: Baseline, Week 24
measure: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24
timeFrame: Baseline, Through Week 24
measure: Absolute Change From Baseline in Lung Clearance Index 5.0 (LCI5.0) Through Week 24
timeFrame: Baseline, Through Week 24
measure: Absolute Change From Baseline in Sweat Chloride at Week 24
timeFrame: Baseline, Week 24
measure: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24
timeFrame: Baseline, Through Week 24
measure: Relative Change From Baseline in ppFEV1 Through Week 24
timeFrame: Baseline, Through Week 24
measure: Absolute Change From Baseline in BMI-for-age Z-score at Week 24
timeFrame: Baseline, Week 24
measure: Absolute Change From Baseline in Weight at Week 24
timeFrame: Baseline, Week 24
measure: Absolute Change From Baseline in Weight-for-age Z-score at Week 24
timeFrame: Baseline, Week 24
measure: Absolute Change From Baseline in Height at Week 24
timeFrame: Baseline, Week 24
measure: Absolute Change From Baseline in Height-for-age Z-score at Week 24
timeFrame: Baseline, Week 24
measure: Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains Through Week 24
timeFrame: Baseline, Through Week 24
measure: Number of Pulmonary Exacerbation Events
timeFrame: Baseline through Week 24
measure: Percentage of Participants With At Least 1 Pulmonary Exacerbation Event
timeFrame: Baseline through Week 24
measure: Time-to-first Pulmonary Exacerbation
timeFrame: Baseline through Week 24
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 28
measure: Average Pre-dose Concentration (Ctrough,Ave) and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Ave) For Lumacaftor and Ivacaftor
timeFrame: 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
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Los Angeles
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: Orlando
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
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: Omaha
country: United States
state: Nebraska
city: Manchester
country: United States
state: New Hampshire
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: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
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: Herston
country: Australia
city: New South Wales
country: Australia
city: Parkville
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: Bordeaux
country: France
city: Bron
country: France
city: Paris Cedex 15
country: France
city: Paris
country: France
city: Berlin
country: Germany
city: Giessen
country: Germany
city: Hannover
country: Germany
city: Koeln
country: Germany
city: Munich
country: Germany
city: Stockholm
country: Sweden
city: Edinburgh
country: United Kingdom
state: Lothian Region
city: Leeds
country: United Kingdom
state: West Yorkshire
city: Belfast
country: United Kingdom
city: London
country: United Kingdom
Study officials:
References:
citation: 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.
citation: Ratjen F, Hug C, Marigowda G, Tian S, Huang X, Stanojevic S, Milla CE, Robinson PD, Waltz D, Davies JC; VX14-809-109 investigator group. Efficacy and safety of lumacaftor and ivacaftor in patients aged 6-11 years with cystic fibrosis homozygous for F508del-CFTR: a randomised, placebo-controlled phase 3 trial. Lancet Respir Med. 2017 Jul;5(7):557-567. doi: 10.1016/S2213-2600(17)30215-1. Epub 2017 Jun 9.