A Study of VX-121 Combination Therapy in Participants With Cystic Fibrosis (CF) Who Are Homozygous for F508del, Heterozygous for F508del and a Gating (F/G) or Residual Function (F/RF) Mutation, or Have At Least 1 Other Triple Combination Responsive (TCR) CFTR Mutation and No F508del Mutation

NCT ID: NCT05076149

Last Updated: 2024-06-13

Study Results

Results available

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

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

597 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-27

Study Completion Date

2023-11-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The purpose of this study is to evaluate the efficacy and safety of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF participants who are homozygous for F508del, heterozygous for F508del and a gating (F/G) or residual function (F/RF) mutation, or have at least 1 other TCR CF transmembrane conductance regulator (CFTR) gene mutation and no F508del mutation.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cystic Fibrosis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

ELX/TEZ/IVA

Following elexacftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) run-in period of 4 weeks, participants received ELX 200 milligram (mg) once daily (qd) /TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the treatment period for 52 weeks.

Group Type ACTIVE_COMPARATOR

ELX/TEZ/IVA

Intervention Type DRUG

Fixed-dose combination tablets for oral administration.

IVA

Intervention Type DRUG

Tablet for oral administration.

Placebo (matched to VX-121/TEZ/D-IVA)

Intervention Type DRUG

Placebo matched to VX-121/TEZ/D-IVA for oral administration.

VX-121/TEZ/D-IVA

Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.

Group Type EXPERIMENTAL

VX-121/TEZ/D-IVA

Intervention Type DRUG

Fixed-dose combination tablets for oral administration.

Placebo (matched to ELX/TEZ/IVA)

Intervention Type DRUG

Placebo matched to ELX/TEZ/IVA for oral administration.

Placebo (matched to IVA)

Intervention Type DRUG

Placebo matched to IVA for oral administration.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

VX-121/TEZ/D-IVA

Fixed-dose combination tablets for oral administration.

Intervention Type DRUG

ELX/TEZ/IVA

Fixed-dose combination tablets for oral administration.

Intervention Type DRUG

IVA

Tablet for oral administration.

Intervention Type DRUG

Placebo (matched to VX-121/TEZ/D-IVA)

Placebo matched to VX-121/TEZ/D-IVA for oral administration.

Intervention Type DRUG

Placebo (matched to ELX/TEZ/IVA)

Placebo matched to ELX/TEZ/IVA for oral administration.

Intervention Type DRUG

Placebo (matched to IVA)

Placebo matched to IVA for oral administration.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

VX-121/VX-661/CTP-656 VX-121/VX-661/VX-561 VX-121/tezacaftor/deutivacaftor VX-445/VX-661/VX-770 elexacaftor/tezacaftor/ivacaftor VX-770 ivacaftor

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Participant has one of the following genotypes:

* Homozygous for F508del;
* Heterozygous for F508del and a gating (F/G) mutation;
* Heterozygous for F508del and a residual function (F/RF) mutation;
* At least 1 other TCR CFTR gene mutation identified as responsive to ELX/TEZ/IVA and no F508del mutation
* Forced expiratory volume in 1 second (FEV1) value \>=40% and \<=90% of predicted mean for age, sex, and height for participants currently receiving CFTR protein modulator therapy; FEV1 \>=40% and \<=80% for participants not currently receiving CFTR protein modulator therapy

Exclusion Criteria

* History of solid organ or hematological transplantation
* Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
* Lung infection with organisms associated with a more rapid decline in pulmonary status
* Pregnant or breast-feeding females
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

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

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

University of California Davis Medical Center

Sacramento, California, United States

Site Status

Children's Hospital of Colorado

Aurora, Colorado, United States

Site Status

National Jewish Health

Denver, Colorado, United States

Site Status

Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

Nemours Children's Specialty Care

Jacksonville, Florida, 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

Nemours Children's Specialty Care, Pensacola

Pensacola, Florida, United States

Site Status

Johns Hopkins All Children's Hospital Outpatient Care Center

St. Petersburg, Florida, United States

Site Status

The Emory Clinic at Chantilly

Atlanta, Georgia, United States

Site Status

St. Luke's Cystic Fibrosis Center of Idaho

Boise, Idaho, United States

Site Status

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

Riley Hospital for Children at Indiana University Health

Indianapolis, Indiana, United States

Site Status

University of Kentucky

Lexington, Kentucky, 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 Clinical Rsearch Center

Boston, Massachusetts, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

UMass Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

Michigan Medicine

Ann Arbor, Michigan, United States

Site Status

Harper University Hospital

Detroit, Michigan, United States

Site Status

Spectrum Health Medical Group Adult Cystic Fibrosis Care Center

Grand Rapids, Michigan, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

The Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Billings Clinic

Billings, Montana, United States

Site Status

Morristown Medical Center

Morristown, New Jersey, United States

Site Status

CF Therapeutics Development Center of Western New York

Buffalo, New York, United States

Site Status

Northwell Health- Long Island Jewish Medical Center

New Hyde Park, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Site Status

Akron Children's Hospital

Akron, 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

Santiago Reyes, M.D.

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

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Prisma Health Richland Campus

Columbia, South Carolina, United States

Site Status

Sanford Children's Speciality Clinic

Sioux Falls, South Dakota, United States

Site Status

University of Tennessee Medical Center

Knoxville, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

The University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Cook Children's Health Care System

Fort Worth, Texas, United States

Site Status

University of Utah - Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

Vermont Lung Center

Colchester, Vermont, United States

Site Status

University of Virginia Health System

Charlottesville, Virginia, United States

Site Status

Children's Hospital of the King's Daughters

Norfolk, Virginia, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Providence Pediatric Pulmonary & Cystic Fibrosis Clinic

Spokane, Washington, United States

Site Status

West Virginia University

Morgantown, West Virginia, United States

Site Status

University Hospital and UW Health Clinics

Madison, Wisconsin, United States

Site Status

Royal Prince Alfred Hospital

Camperdown, , Australia

Site Status

The Prince Charles Hospital

Chermside, , Australia

Site Status

Alfred Hospital

Melbourne, VIC, , Australia

Site Status

Institute for Respiratory Health

Nedlands, , Australia

Site Status

Telethon Kids Institute

Nedlands, , Australia

Site Status

The Royal Children's Hospital

Parkville, VIC, , Australia

Site Status

Sydney Children's Hospital

Randwick, , 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

University of Graz

Graz, , Austria

Site Status

Medizinische Universität Innsbruck

Innsbruck, , Austria

Site Status

Uniklinikum Salzburg - Universitätsklinik für Pneumologie/Lungenheilkunde

Salzburg, , Austria

Site Status

Medizinische Universität Wien

Vienna, , Austria

Site Status

Abteilung fuer Pulmologie Klinikum Wels-Grieskirchen

Wels, , Austria

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

Cliniques Universitaires Saint-Luc

Woluwe-Saint-Lambert, , Belgium

Site Status

University of Calgary Medical Clinic of the Foothills Medical Centre

Calgary, , Canada

Site Status

Stollery Children's Hospital

Edmonton, , Canada

Site Status

St. Joseph's Health Care London

London, , Canada

Site Status

Centre Hospitalier de l'Universite de Montreal (CHUM) Hotel-Dieu

Montreal, , Canada

Site Status

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

Montreal, , Canada

Site Status

Institut Universitaire de Cardiologie et Pneumologie de Quebec - Universite Laval

Québec, , Canada

Site Status

St. Michael's Hospital

Toronto, , Canada

Site Status

British Columbia Children's Hospital

Vancouver, , Canada

Site Status

St. Paul's Hospital

Vancouver, , Canada

Site Status

Aarhus University Hospital

Aarhus, , Denmark

Site Status

Juliane Marie Center, Rigshospitalet

Copenhagen, , Denmark

Site Status

Groupe Hospitaler Pellegrin, CHU De Bordeaux

Bordeaux, , France

Site Status

CHU Lyon - Hopital Femme Mere-Enfant

Bron, , France

Site Status

Centre Hospitalier Intercommunal Creteil

Créteil, , France

Site Status

Institut Cœur Poumon, CHU de Lille

Lille, , France

Site Status

Hopital Arnaud de Villeneuve

Montpellier, , France

Site Status

Centre Hospitalier Universitaire De Nantes - G. R. Laennec

Nantes, , France

Site Status

Centre Hospitalier Universitaire (CHU) de Nice - Hopital Pasteur

Nice, , France

Site Status

Hopital Cochin

Paris, , France

Site Status

Hopital Necker, Enfants Malades

Paris, , France

Site Status

Hopital Robert Debre

Paris, , France

Site Status

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status

Centre de Perharidy

Roscoff, , France

Site Status

CHU de Rouen - Hopital Charles Nicolle

Rouen Cedex, Seine Maritime, , France

Site Status

Hôpital de Hautepierre, AX5

Strasbourg, , France

Site Status

Hopital Foch (Suresnes), Hopital Foch, Adultes

Suresnes, , France

Site Status

Hopital Bretonneau

Tours, , France

Site Status

Centre hospitalier universitaire de Nancy, Hôpital de Braboi

Vandœuvre-lès-Nancy, , 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

Universitatsklinikum Essen (AoR), Kinderklinik III, Abt. fur Pneumologie

Essen, , Germany

Site Status

Justus-Liebig-Universität Gießen Zentrum für Kinderheilkunde und Jugendmedizin

Giessen, , Germany

Site Status

Pneumologisches Studienzentrum Muenchen-West

München, , Germany

Site Status

General Hospital of Thessaloniki "Papanikolaou"

Pilea Chortiatis, , Greece

Site Status

General Hospital of Thessaloniki 'Hippokratio', 3rd Pediatrics Department of Aristotle University of Thessaloniki

Thessaloniki, , Greece

Site Status

National Koranyi Institute for TBC and Pulmonology

Budapest, , Hungary

Site Status

Pulmonology Institute Torokbalint

Törökbálint, , Hungary

Site Status

Cork University Hospital

Cork, , Ireland

Site Status

Children's Health Ireland at Crumlin

Dublin, , Ireland

Site Status

Children's Health Ireland at Tallaght

Dublin, , Ireland

Site Status

Children's University Hospital, Dublin

Dublin, , Ireland

Site Status

St. Vincent's University Hospital

Dublin, , Ireland

Site Status

University Hospital Limerick (Adults)

Limerick, , Ireland

Site Status

University Hospital Limerick (Pediatrics)

Limerick, , Ireland

Site Status

Hadassah Medical Organization

Jerusalem, , Israel

Site Status

Schneider Children's Medical Center of Israel

Petach Tikvah, , Israel

Site Status

Sheba Medical Center - The Edmond and Lili Safra Children's Hospital

Tel Litwinsky, , Israel

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

Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena

Milan, , Italy

Site Status

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Site Status

Malattie Apparato Respiratorio 2 - Centro Fibrosi Cistica

Orbassano, , 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

Academisch Medisch Centrum (Academic Medical Centre)

Amsterdam, , 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

University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis

Utrecht, , Netherlands

Site Status

Greenlane Clinical Centre

Auckland, , New Zealand

Site Status

Starship Children's Hospital

Auckland, , New Zealand

Site Status

Canterbury Respiratory Research Group

Christchurch Hospital, , New Zealand

Site Status

Waikato Hospital

Hamilton, , New Zealand

Site Status

Haukeland Universitetssjukehus (CF)

Bergen, , Norway

Site Status

Oslo University Hospital, Department of Paediatric Medicine

Oslo, , Norway

Site Status

Pediatric Hospital Polanki named of Maciej Płażyński

Gdansk, , Poland

Site Status

Institute of Tuberculosis and Lung Diseases

Rabka-Zdrój, , Poland

Site Status

Klinika Mukowiscydozy IMD Oddozial Chorob Pluc Szpzoz IM. Dzieci WarszaWY

Łomianki, , Poland

Site Status

Sahlgrenska Universitetssjukhuset

Gothenburg, , Sweden

Site Status

Lund University Skanes Universitetssjukhus

Malmo, , Sweden

Site Status

Karolinska Universitetssjukhuset, Huddinge

Stockholm, , Sweden

Site Status

Lindenhofspital - Quartier Bleu

Bern, , Switzerland

Site Status

Réseau Hospitalier Neuchâtelois

Neuchâtel, , Switzerland

Site Status

Kinderspital Zuerich

Zurich, , Switzerland

Site Status

Birmingham Children's Hospital

Birmingham, , United Kingdom

Site Status

Royal Papworth Hospital NHS Foundation Trust

Cambridge, , United Kingdom

Site Status

Clinical Research Facility, Queen Elizabeth University Hospital

Glasgow, , United Kingdom

Site Status

Leeds General Infirmary

Leeds, , United Kingdom

Site Status

St. James University Hospital

Leeds, , United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

Royal Brompton Hospital

London, , United Kingdom

Site Status

St. Bartholomew's Hospital

London, , United Kingdom

Site Status

Royal Manchester Children's Hospital

Manchester, , United Kingdom

Site Status

Wythenshawe Hospital

Manchester, , United Kingdom

Site Status

All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough

Penarth, , United Kingdom

Site Status

Southampton General Hospital

Southampton, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Australia Austria Belgium Canada Denmark France Germany Greece Hungary Ireland Israel Italy Netherlands New Zealand Norway Poland Sweden Switzerland United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Keating C, Yonker LM, Vermeulen F, Prais D, Linnemann RW, Trimble A, Kotsimbos T, Mermis J, Braun AT, O'Carroll M, Sutharsan S, Ramsey B, Mall MA, Taylor-Cousar JL, McKone EF, Tullis E, Floreth T, Michelson P, Sosnay PR, Nair N, Zahigian R, Martin H, Ahluwalia N, Lam A, Horsley A; VX20-121-102 Study Group; VX20-121-103 Study Group. Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials. Lancet Respir Med. 2025 Mar;13(3):256-271. doi: 10.1016/S2213-2600(24)00411-9. Epub 2025 Jan 2.

Reference Type DERIVED
PMID: 39756424 (View on PubMed)

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)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2021-000694-85

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VX20-121-103

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.