Clinical trial NCT01807949: A Study of Lumacaftor in Combination With Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Who Are Homozygous for the F508del-CFTR Mutation
Official title: A Phase 3, Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Lumacaftor in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis, Homozygous for the F508del CFTR Mutation
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2013-03-08
Enrollment: 563
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study was to evaluate the efficacy of lumacaftor in combination with ivacaftor at Week 24 in participants aged 12 years and older with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene.

Detailed description: This was a Phase 3, randomized, double-blind, placebo-controlled, parallel-group multicenter study of orally administered lumacaftor in combination with ivacaftor in participants aged 12 years and older with CF who are homozygous for the F508del-CFTR mutation.

The study included a Screening Period (Day -28 through Day -1), a Treatment Period (Day 1 \[first dose of study drug\] to Week 24 ± 5 days), and a Safety Follow-up Visit (4 weeks ± 7 days after the Week 24 Visit).

Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of CF
* Homozygous for the F508del CFTR mutation
* Forced expiratory volume in 1 second (FEV1) greater than or equal to (\>=) 40 percent (%) and less than or equal to (=\<) 90% of predicted normal for age, sex, and height
* Willing to remain on a stable CF medication regimen through Week 24 or, if applicable, the Safety Follow up Visit

Exclusion Criteria:

* An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before first dose of study drug
* History of solid organ or hematological transplantation
* History of alcohol or drug abuse in the past year
* Ongoing or prior participation in an investigational drug study (including studies investigating lumacaftor and/or ivacaftor) within 30 days of screening.
* Use of strong inhibitors, moderate inducers, or strong inducers of Cytochrome P450 3A (CYP3A) within 14 days before Day 1 of dosing

Primary outcomes:
measure: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 24
timeFrame: Baseline, Week 16 and 24
Secondary outcomes:
measure: Relative Change From Baseline in Percent Predicted FEV1 at Week 24
timeFrame: Baseline, Week 16 and 24
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 at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants With Response Based on Percent Predicted FEV1
timeFrame: Week 16 and 24
measure: Number of Pulmonary Exacerbation Events
timeFrame: through Week 24
measure: Absolute Change From Baseline in Weight at Week 24
timeFrame: Baseline, Week 24
measure: Absolute Change From Baseline in BMI-for-age Z-score at Week 24
timeFrame: Baseline, Week 24
measure: Time-to-First Pulmonary Exacerbation
timeFrame: through Week 24
measure: Percentage of Participants With At Least 1 Pulmonary Exacerbation Event
timeFrame: through Week 24
measure: Absolute Change From Baseline in Euro Quality of Life Scale (EuroQol) 5-Dimension-3 Level (EQ-5D-3L) Index Score at Week 24
timeFrame: Baseline, Week 24
measure: Absolute Change From Baseline in EQ-5D-3L VAS Score at Week 24
timeFrame: Baseline, Week 24
measure: Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domain Scores at Week 24
timeFrame: Baseline, Week 24
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs)
timeFrame: up to Week 28
measure: Pre-dose Concentration (Ctrough), Average Pre-dose Concentration (Ctrough,Avg), 3 to 6 Hours Post-dose Concentration (C3-6h), and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Avg)
timeFrame: For C3-6h: 3 to 6 hours after morning dose on Day 1 and 15, Week 4 and 8; For C3-6h,avg 3 to 6 hours after morning dose on Day 15, Week 4 and 8; For Ctrough and Ctrough,avg: before morning dose on Week 4, 8, and 16
Other outcomes:
Locations:
city: Oakland
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Hartford
country: United States
state: Connecticut
city: New Haven
country: United States
state: Connecticut
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Indianapolis
country: United States
state: Indiana
city: Iowa City
country: United States
state: Iowa
city: Kansas City
country: United States
state: Kansas
city: Lexington
country: United States
state: Kentucky
city: Portland
country: United States
state: Maine
city: Worcester
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Grand Rapids
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Jackson
country: United States
state: Mississippi
city: St. Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Morristown
country: United States
state: New Jersey
city: New Brunswick
country: United States
state: New Jersey
city: Alburquerque
country: United States
state: New Mexico
city: Albany
country: United States
state: New York
city: Buffalo
country: United States
state: New York
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Sioux Falls
country: United States
state: South Dakota
city: Memphis
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Milwaukee
country: United States
state: Wisconsin
city: Brisbane
country: Australia
state: Queensland
city: Chermside
country: Australia
state: Queensland
city: Herston
country: Australia
state: Queensland
city: South Brisbane
country: Australia
state: Queensland
city: Nedlands
country: Australia
state: Western Australia
city: Subiaco
country: Australia
state: Western Australia
city: Innsbruck
country: Austria
city: Wels
country: Austria
city: Bruxelles
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Liège
country: Belgium
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Montreal
country: Canada
state: Quebec
city: København Ø
country: Denmark
city: Marseille
country: France
state: Bouches-du-Rhône
city: Toulouse cedex 9
country: France
state: Haute Garonne
city: Montpellier cedex 5
country: France
state: Herault
city: Lille
country: France
state: Nord
city: Bordeaux Cedex
country: France
city: Paris
country: France
city: Muenchen
country: Germany
state: Bayern
city: Frankfurt
country: Germany
state: Hessen
city: Giessen
country: Germany
state: Hessen
city: Hannover
country: Germany
state: Niederachsen
city: Bochum
country: Germany
state: Nordrhein Westfalen
city: Jena
country: Germany
state: Thueringen
city: Barcelona
country: Spain
city: Valencia
country: Spain
city: Bristol
country: United Kingdom
state: Avon
city: London
country: United Kingdom
state: Greater London
city: Liverpool
country: United Kingdom
state: Merseyside
city: Newcastle upon Tyne
country: United Kingdom
state: Tyne & Wear
city: Leeds
country: United Kingdom
state: West Yorkshire
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: Flume PA, Suthoff ED, Kosinski M, Marigowda G, Quittner AL. Measuring recovery in health-related quality of life during and after pulmonary exacerbations in patients with cystic fibrosis. J Cyst Fibros. 2019 Sep;18(5):737-742. doi: 10.1016/j.jcf.2018.12.004. Epub 2018 Dec 23.
citation: McColley SA, Konstan MW, Ramsey BW, Stuart Elborn J, Boyle MP, Wainwright CE, Waltz D, Vera-Llonch M, Marigowda G, Jiang JG, Rubin JL. Lumacaftor/Ivacaftor reduces pulmonary exacerbations in patients irrespective of initial changes in FEV1. J Cyst Fibros. 2019 Jan;18(1):94-101. doi: 10.1016/j.jcf.2018.07.011. Epub 2018 Aug 23.
citation: Elborn JS, Ramsey BW, Boyle MP, Konstan MW, Huang X, Marigowda G, Waltz D, Wainwright CE; VX-809 TRAFFIC and TRANSPORT study groups. Efficacy and safety of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis homozygous for Phe508del CFTR by pulmonary function subgroup: a pooled analysis. Lancet Respir Med. 2016 Aug;4(8):617-626. doi: 10.1016/S2213-2600(16)30121-7. Epub 2016 Jun 10.
citation: Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, Colombo C, Davies JC, De Boeck K, Flume PA, Konstan MW, McColley SA, McCoy K, McKone EF, Munck A, Ratjen F, Rowe SM, Waltz D, Boyle MP; TRAFFIC Study Group; TRANSPORT Study Group. Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR. N Engl J Med. 2015 Jul 16;373(3):220-31. doi: 10.1056/NEJMoa1409547. Epub 2015 May 17.