Clinical trial NCT05076149: 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
Official title: A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-121 Combination Therapy in Subjects With Cystic Fibrosis 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 CFTR Mutation and No F508del Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2021-10-13
Enrollment: 597
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 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.


Eligibility criteria: Key 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

Key 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

Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Absolute Change in Percent Predicted Forced Expiratory Volume in 1second (ppFEV1)
timeFrame: From Baseline Through Week 24
Secondary outcomes:
measure: Absolute Change in Sweat Chloride (SwCl)
timeFrame: From Baseline Through Week 24
measure: Percentage of Participants With SwCl <60 Millimole Per Liter (mmol/L) (Pooled With Data From Study VX20-121-102)
timeFrame: From Baseline Through Week 24
measure: Percentage of Participants With SwCl <30 mmol/L (Pooled With Data From Study VX20-121-102)
timeFrame: From Baseline Through Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: Banner University of Arizona Medical Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Jacksonville
country: United States
facility: Nemours Children's Specialty Care
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary Group, PA
state: Florida
city: Pensacola
country: United States
facility: Nemours Children's Specialty Care, Pensacola
state: Florida
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital Outpatient Care Center
state: Florida
city: Atlanta
country: United States
facility: The Emory Clinic at Chantilly
state: Georgia
city: Boise
country: United States
facility: St. Luke's Cystic Fibrosis Center of Idaho
state: Idaho
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Indianapolis
country: United States
facility: Riley Hospital for Children at Indiana University Health
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: Tulane Medical Center
state: Louisiana
city: Portland
country: United States
facility: Maine Medical Partners
state: Maine
city: Boston
country: United States
facility: Massachusetts General Hospital Cystic Fibrosis Center Clinical Rsearch Center
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Medicine
state: Michigan
city: Detroit
country: United States
facility: Harper University Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Medical Group Adult Cystic Fibrosis Care Center
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: The Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: CF Therapeutics Development Center of Western New York
state: New York
city: New Hyde Park
country: United States
facility: Northwell Health- Long Island Jewish Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: Dayton Children's Hospital
state: Ohio
city: Toledo
country: United States
facility: ProMedica Toledo Hospital/Toledo Children's Hospital/Pediatric Pulmonary & Cystic Fibrosis Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Santiago Reyes, M.D.
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Columbia
country: United States
facility: Prisma Health Richland Campus
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford Children's Speciality Clinic
state: South Dakota
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Health Care System
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah - Primary Children's Medical Center
state: Utah
city: Colchester
country: United States
facility: Vermont Lung Center
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Spokane
country: United States
facility: Providence Pediatric Pulmonary & Cystic Fibrosis Clinic
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Madison
country: United States
facility: University Hospital and UW Health Clinics
state: Wisconsin
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
city: Chermside
country: Australia
facility: The Prince Charles Hospital
city: Melbourne, VIC
country: Australia
facility: Alfred Hospital
city: Nedlands
country: Australia
facility: Institute for Respiratory Health
city: Nedlands
country: Australia
facility: Telethon Kids Institute
city: Parkville, VIC
country: Australia
facility: The Royal Children's Hospital
city: Randwick
country: Australia
facility: Sydney Children's Hospital
city: South Brisbane
country: Australia
facility: Mater Adult Hospital
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Graz
country: Austria
facility: University of Graz
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Salzburg
country: Austria
facility: Uniklinikum Salzburg - Universitätsklinik für Pneumologie/Lungenheilkunde
city: Vienna
country: Austria
facility: Medizinische Universität Wien
city: Wels
country: Austria
facility: Abteilung fuer Pulmologie Klinikum Wels-Grieskirchen
city: Brussel
country: Belgium
facility: Cliniques Universitaires de Bruxelles Hopital Erasme
city: Brussel
country: Belgium
facility: Universitair Ziekenhuis Brussel - Campus Jette
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
city: Woluwe-Saint-Lambert
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Calgary
country: Canada
facility: University of Calgary Medical Clinic of the Foothills Medical Centre
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
city: London
country: Canada
facility: St. Joseph's Health Care London
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM) Hotel-Dieu
city: Montréal
country: Canada
facility: McGill University Health Centre, Glen Site, Montreal Children's Hospital
city: Québec
country: Canada
facility: Institut Universitaire de Cardiologie et Pneumologie de Quebec - Universite Laval
city: Toronto
country: Canada
facility: St. Michael's Hospital
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
city: Vancouver
country: Canada
facility: St. Paul's Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Juliane Marie Center, Rigshospitalet
city: Bordeaux cedex
country: France
facility: Groupe Hospitaler Pellegrin, CHU De Bordeaux
city: Bron Cedex
country: France
facility: CHU Lyon - Hopital Femme Mere-Enfant
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal Creteil
city: Lille
country: France
facility: Institut Cœur Poumon, CHU de Lille
city: Montpellier Cedex 5
country: France
facility: Hopital Arnaud de Villeneuve
city: Nantes
country: France
facility: Centre Hospitalier Universitaire De Nantes - G. R. Laennec
city: Nice
country: France
facility: Centre Hospitalier Universitaire (CHU) de Nice - Hopital Pasteur
city: Paris Cedex 15
country: France
facility: Hopital Necker, Enfants Malades
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: Hopital Robert Debre
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Roscoff cedex
country: France
facility: Centre de Perharidy
city: Rouen Cedex, Seine Maritime
country: France
facility: CHU de Rouen - Hopital Charles Nicolle
city: Strasbourg
country: France
facility: Hôpital de Hautepierre, AX5
city: Suresnes
country: France
facility: Hopital Foch (Suresnes), Hopital Foch, Adultes
city: Tours
country: France
facility: Hopital Bretonneau
city: Vandoeuvre Les Nancy
country: France
facility: Centre hospitalier universitaire de Nancy, Hôpital de Braboi
city: Berlin
country: Germany
facility: Charite Paediatric Pulmonology Department
city: Erlangen
country: Germany
facility: Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital
city: Essen
country: Germany
facility: Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
city: Essen
country: Germany
facility: Universitatsklinikum Essen (AoR), Kinderklinik III, Abt. fur Pneumologie
city: Gießen
country: Germany
facility: Justus-Liebig-Universität Gießen Zentrum für Kinderheilkunde und Jugendmedizin
city: Muenchen
country: Germany
facility: Pneumologisches Studienzentrum Muenchen-West
city: Pilea Chortiatis
country: Greece
facility: General Hospital of Thessaloniki "Papanikolaou"
city: Thessaloníki
country: Greece
facility: General Hospital of Thessaloniki 'Hippokratio', 3rd Pediatrics Department of Aristotle University of Thessaloniki
city: Budapest
country: Hungary
facility: National Koranyi Institute for TBC and Pulmonology
city: Torokbalint
country: Hungary
facility: Pulmonology Institute Torokbalint
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Children's Health Ireland at Crumlin
city: Dublin
country: Ireland
facility: Children's Health Ireland at Tallaght
city: Dublin
country: Ireland
facility: Children's University Hospital, Dublin
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital
city: Limerick
country: Ireland
facility: University Hospital Limerick (Adults)
city: Limerick
country: Ireland
facility: University Hospital Limerick (Pediatrics)
city: Jerusalem
country: Israel
facility: Hadassah Medical Organization
city: Petach Tikvah
country: Israel
facility: Schneider Children's Medical Center of Israel
city: Tel HaShomer
country: Israel
facility: Sheba Medical Center - The Edmond and Lili Safra Children's Hospital
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedale Riuniti
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer
city: Genova
country: Italy
facility: IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Milan
country: Italy
facility: Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
city: Orbassano
country: Italy
facility: Malattie Apparato Respiratorio 2 - Centro Fibrosi Cistica
city: Potenza
country: Italy
facility: Centro Regionale Fibrosi Cistica, A.O. Ospedale San Carlo
city: Verona
country: Italy
facility: Azienda Ospedaliera di Verona - Ospedale Civile Maggiore
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum (Academic Medical Centre)
city: Den Haag
country: Netherlands
facility: HagaZiekenhuis van den Haag
city: Nijmegen
country: Netherlands
facility: UMC St. Radboud
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Utrecht
country: Netherlands
facility: University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
city: Auckland
country: New Zealand
facility: Greenlane Clinical Centre
city: Auckland
country: New Zealand
facility: Starship Children's Hospital
city: Christchurch Hospital
country: New Zealand
facility: Canterbury Respiratory Research Group
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Bergen
country: Norway
facility: Haukeland Universitetssjukehus (CF)
city: Oslo
country: Norway
facility: Oslo University Hospital, Department of Paediatric Medicine
city: Gdańsk
country: Poland
facility: Pediatric Hospital Polanki named of Maciej Płażyński
city: Rabka Zdrój
country: Poland
facility: Institute of Tuberculosis and Lung Diseases
city: Łomianki
country: Poland
facility: Klinika Mukowiscydozy IMD Oddozial Chorob Pluc Szpzoz IM. Dzieci WarszaWY
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Malmoe
country: Sweden
facility: Lund University Skanes Universitetssjukhus
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset, Huddinge
city: Bern
country: Switzerland
facility: Lindenhofspital - Quartier Bleu
city: Neuchâtel
country: Switzerland
facility: Réseau Hospitalier Neuchâtelois
city: Zürich
country: Switzerland
facility: Kinderspital Zuerich
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital NHS Foundation Trust
city: Glasgow
country: United Kingdom
facility: Clinical Research Facility, Queen Elizabeth University Hospital
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: Leeds
country: United Kingdom
facility: St. James University Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: London
country: United Kingdom
facility: St. Bartholomew's Hospital
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
city: Penarth
country: United Kingdom
facility: All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
References: