Clinical trial NCT01807923: 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: 559
Sex: ALL
Minimum age (years): 12
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 Serious Treatment-Emergent 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:
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state: New Hampshire
city: Lebanon
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city: Long Branch
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state: New Jersey
city: Hawthorne
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state: New York
city: New York
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state: New York
city: Valhalla
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state: New York
city: Chapel Hill
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state: North Carolina
city: Durham
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state: Vermont
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state: Virginia
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city: Seattle
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city: Morgantown
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state: West Virginia
city: Madison
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state: Wisconsin
city: Broadmeadow
country: Australia
state: New South Wales
city: Westmead
country: Australia
state: New South Wales
city: Adelaide
country: Australia
state: South Australia
city: Halifax
country: Canada
state: British Columbia
city: Vancouver
country: Canada
state: British Columbia
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Brno
country: Czech Republic
city: Plzen-Bory
country: Czech Republic
city: Praha 5
country: Czech Republic
city: Strasbourg Cedex 2
country: France
state: Bas Rhin
city: Roscoff
country: France
state: Finistere
city: Paris Cedex 14
country: France
state: Paris
city: Paris Cedex 15
country: France
state: Paris
city: Bron Cedex
country: France
state: Rhone
city: Pierre Benite
country: France
state: Rhone
city: Tuebingen
country: Germany
state: Baden Wuerttemberg
city: Erlangen
country: Germany
state: Bayern
city: Wuerzburg
country: Germany
state: Bayern
city: Koeln
country: Germany
state: Nordrhein Westfalen
city: Leipzig
country: Germany
state: Sachsen
city: Berlin
country: Germany
city: Tallaght
country: Ireland
state: Dublin
city: Dublin
country: Ireland
city: Ancona
country: Italy
city: Firenze
country: Italy
city: Genova
country: Italy
city: Milano
country: Italy
city: Roma
country: Italy
city: Verona
country: Italy
city: Amsterdam
country: Netherlands
city: Den Haag
country: Netherlands
city: Nijmegen
country: Netherlands
city: Rotterdam
country: Netherlands
city: Goteborg
country: Sweden
city: Stockholm
country: Sweden
city: Uppsala
country: Sweden
city: Exeter
country: United Kingdom
state: Devon
city: Southhampton
country: United Kingdom
state: Hampshire
city: Nottingham
country: United Kingdom
state: Nottinghamshire
city: Birmingham
country: United Kingdom
state: West Midlands
city: Belfast
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: 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.