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

NCT ID: NCT01807923

Last Updated: 2015-08-31

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

559 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-05-31

Study Completion Date

2014-04-30

Brief Summary

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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

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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).

Conditions

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Cystic Fibrosis, Homozygous for the F508del CFTR Mutation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Placebo

Placebo matched to lumacaftor (LUM, VX-809) and ivacaftor (IVA, VX-770) tablet every 12 hours (q12h), up to Week 24.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matching placebo tablet

LUM 600 mg qd/IVA 250 mg q12h

LUM 600 milligram (mg) plus IVA 250 mg fixed-dose combination (FDC) tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.

Group Type EXPERIMENTAL

Lumacaftor Plus Ivacaftor Combination

Intervention Type DRUG

Fixed dose combination tablet

Ivacaftor

Intervention Type DRUG

Film-coated tablet

LUM 400 mg q12h/ IVA 250 mg q12h

LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.

Group Type EXPERIMENTAL

Lumacaftor Plus Ivacaftor Combination

Intervention Type DRUG

Fixed dose combination tablet

Interventions

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Lumacaftor Plus Ivacaftor Combination

Fixed dose combination tablet

Intervention Type DRUG

Ivacaftor

Film-coated tablet

Intervention Type DRUG

Placebo

Matching placebo tablet

Intervention Type DRUG

Other Intervention Names

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VX-809+VX-770, LUM+IVA VX-770, IVA

Eligibility Criteria

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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
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Birmingham, Alabama, United States

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Anchorage, Alaska, United States

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Tucson, Arizona, United States

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Little Rock, Arkansas, United States

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Fresno, California, United States

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La Jolla, California, United States

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Loma Linda, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Madera, California, United States

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Oakland, California, United States

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Palo Alto, California, United States

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Denver, Colorado, United States

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Gainsville, Florida, United States

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Hollywood, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Boise, Idaho, United States

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Chicago, Illinois, United States

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Park Ridge, Illinois, United States

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Peoria, Illinois, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Kansas City, Missouri, United States

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Bedford, New Hampshire, United States

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Lebanon, New Hampshire, United States

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Long Branch, New Jersey, United States

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Hawthorne, New York, United States

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New York, New York, United States

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Valhalla, New York, United States

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Chapel Hill, North Carolina, United States

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Durham, North Carolina, United States

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Akron, Ohio, United States

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Cincinnati, Ohio, United States

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Dayton, Ohio, United States

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Portland, Oregon, United States

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Hershey, Pennsylvania, United States

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Knoxville, Tennessee, United States

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Austin, Texas, United States

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Tyler, Texas, United States

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Colchester, Vermont, United States

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Charlottesville, Virginia, United States

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Norfolk, Virginia, United States

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Seattle, Washington, United States

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Morgantown, West Virginia, United States

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Madison, Wisconsin, United States

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Broadmeadow, New South Wales, Australia

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Westmead, New South Wales, Australia

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Adelaide, South Australia, Australia

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Halifax, British Columbia, Canada

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Vancouver, British Columbia, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Brno, , Czechia

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Plzen-Bory, , Czechia

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Prague, , Czechia

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Strasbourg, Bas Rhin, France

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Roscoff, Finistere, France

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Paris, Paris, France

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Bron, Rhone, France

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Pierre-Bénite, Rhone, France

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Tübingen, Baden-Wurttemberg, Germany

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Erlangen, Bavaria, Germany

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Würzburg, Bavaria, Germany

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Cologne, North Rhine-Westphalia, Germany

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Leipzig, Saxony, Germany

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Berlin, State of Berlin, Germany

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Dublin, Dublin, Ireland

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Tallaght, Dublin, Ireland

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Florence, Firenze, Italy

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Ancona, , Italy

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Genova, , Italy

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Milan, , Italy

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Roma, , Italy

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Verona, , Italy

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Amsterdam, , Netherlands

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Nijmegen, , Netherlands

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Rotterdam, , Netherlands

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The Hague, , Netherlands

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Gothenburg, , Sweden

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Stockholm, , Sweden

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Uppsala, , Sweden

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Belfast, Belfast, United Kingdom

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Exeter, Devon, United Kingdom

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Southhampton, Hampshire, United Kingdom

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Nottingham, Nottinghamshire, United Kingdom

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Birmingham, West Midlands, United Kingdom

Site Status

Countries

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United States Australia Canada Czechia France Germany Ireland Italy Netherlands Sweden United Kingdom

References

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Heneghan M, 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. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.

Reference Type DERIVED
PMID: 37983082 (View on PubMed)

Acaster S, Mukuria C, Rowen D, Brazier JE, Wainwright CE, Quon BS, Duckers J, Quittner AL, Lou Y, Sosnay PR, McGarry LJ. Development of the Cystic Fibrosis Questionnaire-Revised-8 Dimensions: Estimating Utilities From the Cystic Fibrosis Questionnaire-Revised. Value Health. 2023 Apr;26(4):567-578. doi: 10.1016/j.jval.2022.12.002. Epub 2022 Dec 9.

Reference Type DERIVED
PMID: 36509366 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33331662 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30587335 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30146268 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27298017 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25981758 (View on PubMed)

Other Identifiers

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VX12-809-103

Identifier Type: -

Identifier Source: org_study_id