A Phase 3 Study of VX-445 Combination Therapy in Cystic Fibrosis (CF) Subjects Heterozygous for F508del and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)

NCT ID: NCT04058353

Last Updated: 2021-07-02

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

271 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-28

Study Completion Date

2020-06-12

Brief Summary

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This study will evaluate the efficacy, safety and pharmacodynamics of elexacaftor (ELX, 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 gating or residual function mutation (F/G and F/RF genotypes).

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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Control: IVA or TEZ/IVA

Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 milligrams (mg) every 12 hours (q12h) or TEZ 100 mg once daily (qd)/IVA 150 mg q12h in the treatment period for 8 weeks.

Group Type ACTIVE_COMPARATOR

IVA

Intervention Type DRUG

Mono-tablet for oral administration.

TEZ/IVA

Intervention Type DRUG

Fixed-dose combination (FDC) tablet for oral administration.

TC: ELX/TEZ/IVA

Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.

Group Type EXPERIMENTAL

ELX/TEZ/IVA

Intervention Type DRUG

FDC tablet for oral administration.

IVA

Intervention Type DRUG

Mono-tablet for oral administration.

Interventions

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ELX/TEZ/IVA

FDC tablet for oral administration.

Intervention Type DRUG

IVA

Mono-tablet for oral administration.

Intervention Type DRUG

TEZ/IVA

Fixed-dose combination (FDC) tablet for oral administration.

Intervention Type DRUG

Other Intervention Names

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

Eligibility Criteria

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Inclusion Criteria

* Subject has a confirmed diagnosis of CF and is heterozygous for F508del and either a gating or residual function mutation (F/G and F/RF genotypes)
* 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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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Banner University of Arizona Medical Center

Tucson, Arizona, United States

Site Status

Miller Children's Hospital / Long Beach Memorial

Long Beach, California, United States

Site Status

Stanford University

Palo Alto, California, United States

Site Status

University of California Davis Medical Center

Sacramento, California, United States

Site Status

University of California San Francisco, Lung Transplant Program

San Francisco, California, United States

Site Status

National Jewish Health

Denver, Colorado, United States

Site Status

University of Miami Miller School of Medicine

Miami, Florida, United States

Site Status

Central Florida Pulmonary Group, PA

Orlando, Florida, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

The University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Massachusetts General Hospital Cystic Fibrosis Center Clinical Rsearch Center

Boston, Massachusetts, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

Michigan Medicine

Ann Arbor, Michigan, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Washington University School of Medicine / St. Louis Children's Hospital

St Louis, Missouri, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Northwell Health- Long Island Jewish Medical Center

New Hyde Park, New York, United States

Site Status

Mount Sinai Beth Israel

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

University of North Carolina Hospitals

Chapel Hill, North Carolina, United States

Site Status

UC Health Holmes

Cincinnati, Ohio, United States

Site Status

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

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, 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

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Dell Children's Medical Group

Austin, Texas, United States

Site Status

The University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Texas Children's Hospital

Houston, Texas, United States

Site Status

University of Utah / Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

The Prince Charles Hospital

Chermside, , Australia

Site Status

Alfred Hospital

Melbourne, VIC, , Australia

Site Status

Perth Children's Hospital

Nedlands, , Australia

Site Status

The Royal Children's Hospital

Parkville, VIC, , Australia

Site Status

Mater Adult Hospital

South Brisbane, , Australia

Site Status

Queensland Children's Hospital

South Brisbane, , Australia

Site Status

Westmead Hospital

Westmead, , Australia

Site Status

Cliniques Universitaires de Bruxelles Hopital Erasme

Brussels, , Belgium

Site Status

Universitair Ziekenhuis Brussel - Campus Jette

Brussels, , Belgium

Site Status

Universitair Ziekenhuis Gent

Ghent, , Belgium

Site Status

Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg

Leuven, , Belgium

Site Status

Stollery Children's Hospital

Edmonton, , Canada

Site Status

McGill University Health Center

Québec, , Canada

Site Status

St. Michael's Hospital

Toronto, , Canada

Site Status

St. Paul's Hospital

Vancouver, , Canada

Site Status

Juliane Marie Center, Rigshospitalet

Copenhagen, , Denmark

Site Status

Centre Hospitalier Lyon Sud

Benite Cedex, , France

Site Status

Groupe Hospitaler Pellegrin, CHU De Bordeaux

Bordeaux, , France

Site Status

CHRU de Lille - Hopital Albert Calmette

Lille, , France

Site Status

CHU Marseille - Hopital Nord

Marseille, , France

Site Status

CHU de Montpellier - Hopital Arnaud de Villeneuve

Montpellier, , France

Site Status

Hopital Cochin

Paris, , France

Site Status

Hopital Necker, Enfants Malades

Paris, , France

Site Status

Hopital Pontchaillou CHU de Rennes

Rennes, , France

Site Status

Charite Paediatric Pulmonology Department

Berlin, , Germany

Site Status

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

Erlangen, , Germany

Site Status

Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen

Essen, , Germany

Site Status

Justus-Liebig-Universitaet Gießen Zentrum fur Kinderheilkunde und Jugendmedizin

Giessen, , Germany

Site Status

Universitätsklinikum Halle (Saale) / Universitätsklinik und Poliklinik für Innere Medizin, Schwerpunkt Pneumologie

Halle, , Germany

Site Status

Pneumologisches Studienzentrum Muenchen-West

München, , Germany

Site Status

University Hospital Wuerzburg

Würzburg, , Germany

Site Status

Cork University Hospital

Cork, , Ireland

Site Status

Beaumont Hospital

Dublin, , Ireland

Site Status

St. Vincent's University Hospital

Dublin, , Ireland

Site Status

University Hospital Limerick (Adults)

Limerick, , Israel

Site Status

Azienda Ospedaliero Universitaria Ospedale Riuniti

Ancona, , Italy

Site Status

IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico

Genova, , Italy

Site Status

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Site Status

Malattie Apparato Respiratorio 2 - Fibrosi Cistica

Orbassano, , Italy

Site Status

Ospedale Pediatrico Bambino Gesu

Rome, , Italy

Site Status

Azienda Ospedaliera di Verona-Ospedale Civile Maggiore

Verona, , Italy

Site Status

University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis

Heidelberglaan, , Netherlands

Site Status

UMC St. Radboud

Nijmegen, , Netherlands

Site Status

HagaZiekenhuis van den Haag

The Hague, , Netherlands

Site Status

Hospital Universitari Vall d´Hebron Servicio de Broncoscopia

Barcelona, , Spain

Site Status

Hospital Virgen de la Arrixaca

Murcia, , Spain

Site Status

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Hospital Universitario y Politecnico La Fe

Valencia, , Spain

Site Status

Papworth Hospital NHS Foundation Trust, Papworth Everard

Cambridge, , United Kingdom

Site Status

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

Exeter, , United Kingdom

Site Status

Clinical Research Facility, Queen Elizabeth University Hospital

Glasgow, , United Kingdom

Site Status

St. James University Hospital

Leeds, , United Kingdom

Site Status

Liverpool Heart and Chest Hospital

Liverpool, , United Kingdom

Site Status

Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital

London, , United Kingdom

Site Status

Wythenshawe Hospital

Manchester, , United Kingdom

Site Status

Southampton General Hospital

Southampton, , United Kingdom

Site Status

Countries

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United States Australia Belgium Canada Denmark France Germany Ireland Israel Italy Netherlands Spain United Kingdom

References

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Barry PJ, Mall MA, Alvarez A, Colombo C, de Winter-de Groot KM, Fajac I, McBennett KA, McKone EF, Ramsey BW, Sutharsan S, Taylor-Cousar JL, Tullis E, Ahluwalia N, Jun LS, Moskowitz SM, Prieto-Centurion V, Tian S, Waltz D, Xuan F, Zhang Y, Rowe SM, Polineni D; VX18-445-104 Study Group. Triple Therapy for Cystic Fibrosis Phe508del-Gating and -Residual Function Genotypes. N Engl J Med. 2021 Aug 26;385(9):815-825. doi: 10.1056/NEJMoa2100665.

Reference Type DERIVED
PMID: 34437784 (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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2018-002835-76

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VX18-445-104

Identifier Type: -

Identifier Source: org_study_id

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