A Phase 3 Study of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)

NCT ID: NCT03525444

Last Updated: 2020-05-19

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

405 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-06-15

Study Completion Date

2019-04-24

Brief Summary

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This study will evaluate the efficacy of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a minimal function mutation (F/MF subjects).

Detailed Description

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Conditions

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Cystic Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Participants who received placebo matched to VX-445/TEZ/IVA for 24 weeks in the TC treatment period.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Participants received placebo matched VX-445/TEZ/IVA orally once daily in the morning and placebo matched to IVA orally once daily in the evening.

VX-445/TEZ/IVA TC

Participants who received VX-445 200 mg/TEZ 100 mg/IVA150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 weeks in the TC treatment period.

Group Type EXPERIMENTAL

VX-445/TEZ/IVA

Intervention Type DRUG

Participants received VX-445/TEZ/IVA orally once daily in the morning.

IVA

Intervention Type DRUG

Participants received IVA orally once daily in the evening

Interventions

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VX-445/TEZ/IVA

Participants received VX-445/TEZ/IVA orally once daily in the morning.

Intervention Type DRUG

IVA

Participants received IVA orally once daily in the evening

Intervention Type DRUG

Placebo

Participants received placebo matched VX-445/TEZ/IVA orally once daily in the morning and placebo matched to IVA orally once daily in the evening.

Intervention Type DRUG

Other Intervention Names

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VX-445/VX-661/VX-770 VX-445/tezacaftor/ivacaftor VX-770 ivacaftor

Eligibility Criteria

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Inclusion Criteria

* Heterozygous for the F508del mutation (F/MF)
* Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height

Exclusion Criteria

* Clinically significant cirrhosis with or without portal hypertension
* Lung infection with organisms associated with a more rapid decline in pulmonary status
* Solid organ or hematological transplantation
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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Banner University of Arizona Medical Center

Tucson, Arizona, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Miller Children's Hospital/ Long Beach Memorial

Long Beach, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Valley Children's Hospital/ Children's Hospital of Central California

Madera, California, United States

Site Status

Kaiser Permanente

Oakland, California, United States

Site Status

University of California Davis Medical Center

Sacramento, California, United States

Site Status

UCSF Gateway Medical Center

San Francisco, California, United States

Site Status

National Jewish Health

Denver, Colorado, United States

Site Status

University of Florida, Shands Hospital

Gainesville, Florida, United States

Site Status

Joe DiMaggio Cystic Fibrosis & Pulmonary Center/ Joe DiMaggio Children's Hospital/ Memorial Regional Hospital

Hollywood, Florida, United States

Site Status

Nemours Children's Specialty Care

Jacksonville, Florida, United States

Site Status

Central Florida Pulmonary Group

Orlando, Florida, United States

Site Status

Nemours Children's Hospital

Orlando, Florida, United States

Site Status

Tampa General Hospital Cardiac and Lung Transplant Clinic

Tampa, Florida, United States

Site Status

Children's Speciality Services at North Druid Hills

Atlanta, Georgia, United States

Site Status

Augusta University

Augusta, Georgia, United States

Site Status

Ann & Robert Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

Saint Francis Medical Center/ Children's Hospital of Illinois/OSF

Peoria, Illinois, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Tulane Medical Center

New Orleans, Louisiana, United States

Site Status

Maine Medical Partners

Portland, Maine, United States

Site Status

Massachusetts General Hospital Cystic Fibrosis Center

Boston, Massachusetts, United States

Site Status

Harper University Hospital

Detroit, Michigan, United States

Site Status

Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, United States

Site Status

Billings Clinic

Billings, Montana, United States

Site Status

Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Morristown Medical Center

Morristown, New Jersey, United States

Site Status

University of New Mexico Clinical & Translational Science Center

Albuquerque, New Mexico, United States

Site Status

Mount Sinai Beth Israel

New York, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

UNC Marsico Clinical Research Center

Chapel Hill, North Carolina, United States

Site Status

Akron Children's Hospital

Akron, Ohio, United States

Site Status

UC Health Holmes

Cincinnati, Ohio, United States

Site Status

University Hospitals Cleveland Medical Center/ Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Dayton Children's Hospital

Dayton, Ohio, United States

Site Status

ProMedica Toledo Hospital/ Toledo Children's Hospital/ Pediatric Pulmonary & Cystic Fibrosis Center

Toledo, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Austin Children's Chest Associates

Austin, Texas, United States

Site Status

The University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

The University of Texas Health Science Center at Tyler

Tyler, Texas, United States

Site Status

Vermont Lung Center

Colchester, Vermont, United States

Site Status

University of Virginia Primary Care Center

Charlottesville, Virginia, United States

Site Status

Children's Hospital of the King's Daughters

Norfolk, Virginia, United States

Site Status

Children's Hospital of Richmond at VCU, Children's Pavilion

Richmond, Virginia, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

West Virginia University

Morgantown, West Virginia, United States

Site Status

University of Wisconsin Hospitals and Clinics

Madison, Wisconsin, United States

Site Status

CTSI Adult Translational Research Unit/Medical College of Wisconsin/Froedtert Hospital

Milwaukee, Wisconsin, United States

Site Status

Women & Children's Hospital

North Adelaide, , Australia

Site Status

The Royal Children's Hospital

Parkville, , Australia

Site Status

Mater Adult Hospital

South Brisbane, , Australia

Site Status

The Children's Hospital at Westmead

Westmead, , Australia

Site Status

Westmead Hospital

Westmead, , Australia

Site Status

University of Graz

Graz, , Austria

Site Status

Medizinische Universitat Innsbruck

Innsbruck, , Austria

Site Status

LKH - Universitätsklinikum der PMU Salzburg

Salzburg, , Austria

Site Status

Medizinische Universitat Wien

Vienna, , Austria

Site Status

Cliniques Universitaires de Bruxelles Hopital Erasme

Brussels, , Belgium

Site Status

Universitair Ziekenhuis Brussel - Campus Jette

Brussels, , Belgium

Site Status

UZ Antwerpen

Edegem, , Belgium

Site Status

Universitair Ziekenhuis Gent

Ghent, , Belgium

Site Status

Universitaire Ziekenhuizen Leuven - Campus Gathuisberg

Leuven, , Belgium

Site Status

British Columbia's Children's Hospital

Vancouver, British Columbia, Canada

Site Status

St. Paul's Hospital

Vancouver, British Columbia, Canada

Site Status

McGill University Health Centre, Glen Site, Montreal Children's Hospital

Montreal, Quebec, Canada

Site Status

University of Calgary Medical Clinic of the Foothills Medical Centre

Calgary, , Canada

Site Status

Centre Hospitalier De L'Universite Laval

Qubec, , Canada

Site Status

Saint John Regional Hospital

Saint John, , Canada

Site Status

The Hospital for Sick Children

Toronto, , Canada

Site Status

Vancouver Island Health Authority

Victoria, , Canada

Site Status

Fakultni Nemocnice Brno

Brno, , Czechia

Site Status

Fakultni nemocnice v Motole

Prague, , Czechia

Site Status

Centre Hospitalier Lyon Sud

Benite Cedex, , France

Site Status

Groupe Hospitaler Pellegrin, CHU De Bordeaux

Bordeaux, , France

Site Status

CHU Marseille - Hopital Nord

Marseille, , France

Site Status

CHU de Nice - Hopital Pasteur

Nice, , France

Site Status

Hopital Cochin

Paris, , France

Site Status

CHU de Rouen - Hopital Charles Nicolle

Rouen Cedex, Seine Maritime, , France

Site Status

Hopital Foch (Suresnes), Hopital Foch, Adultes

Suresnes, , France

Site Status

Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital

Erlangen, , Germany

Site Status

Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin

Giessen, , Germany

Site Status

Hannover Medical School

Hanover, , Germany

Site Status

Heidelberg Cystic Fibrosis Center

Heidelberg, , Germany

Site Status

Johannes Gutenberg-Universitaet

Mainz, , Germany

Site Status

Dr. von Haunersches Kinderspital

München, , Germany

Site Status

Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin

Tübingen, , Germany

Site Status

University Hospital Wuerzburg

Würzburg, , Germany

Site Status

General Hospital of Attika "Sismanoglio"(Adult CF center, NHS)

Marousi, , Greece

Site Status

Azienda Ospedaliero Universitaria Ospedale Riuniti

Ancona, , Italy

Site Status

Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer

Florence, , Italy

Site Status

IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico

Genova, , Italy

Site Status

Azienda Ospedaliera Universitaria Policlinico G. Martino

Messina, , Italy

Site Status

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Site Status

Centro Regionale Fibrosi Cistica, A.O. Ospedale San Carlo

Potenza, , Italy

Site Status

Azienda Ospedaliera di Verona-Ospedale Civile Maggiore

Verona, , Italy

Site Status

Academic Medical Center

Amsterdam, , Netherlands

Site Status

University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis

Heidelberglaan, , Netherlands

Site Status

UMC St. Radboud

Nijmegen, , Netherlands

Site Status

Erasmus Medical Center

Rotterdam, , Netherlands

Site Status

HagaZiekenhuis van den Haag

The Hague, , Netherlands

Site Status

Karolinska Univeritetssjukhuset, Huddinge

Stockholm, , Sweden

Site Status

The Royal Belfast Hospital for Sick Children

Belfast, , United Kingdom

Site Status

Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital

Brimingham, , United Kingdom

Site Status

Royal Hospital for Sick Children

Edinburgh, , United Kingdom

Site Status

Western General Hospital

Edinburgh, , United Kingdom

Site Status

Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital

Exeter, , United Kingdom

Site Status

Leeds General Infirmary

Leeds, , United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

Royal Manchester Children's Hospital

Manchester, , United Kingdom

Site Status

Southampton General Hospital

Southampton, , United Kingdom

Site Status

Countries

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United States Australia Austria Belgium Canada Czechia France Germany Greece 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)

Middleton PG, Mall MA, Drevinek P, Lands LC, McKone EF, Polineni D, Ramsey BW, Taylor-Cousar JL, Tullis E, Vermeulen F, Marigowda G, McKee CM, Moskowitz SM, Nair N, Savage J, Simard C, Tian S, Waltz D, Xuan F, Rowe SM, Jain R; VX17-445-102 Study Group. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019 Nov 7;381(19):1809-1819. doi: 10.1056/NEJMoa1908639. Epub 2019 Oct 31.

Reference Type DERIVED
PMID: 31697873 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2018-000183-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VX17-445-102

Identifier Type: -

Identifier Source: org_study_id

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