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

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: IVA; Drug: VX-121/TEZ/D-IVA; Drug: Placebo (matched to ELX/TEZ/IVA); Drug: Placebo (matched to IVA); Drug: ELX/TEZ/IVA; Drug: Placebo (matched to VX-121/TEZ/D-IVA)

• Study Type: Interventional
• Enrollment (Actual): 600
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia
    • Royal Prince Alfred Hospital
  • Chermside, Australia
    • The Prince Charles Hospital
  • Melbourne, VIC, Australia
    • Alfred Hospital
  • Nedlands, Australia
    • Institute for Respiratory Health
  • Nedlands, Australia
    • Telethon Kids Institute
  • Parkville, VIC, Australia
    • The Royal Children's Hospital
  • Randwick, Australia
    • Sydney Children's Hospital
  • South Brisbane, Australia
    • Queensland Children's Hospital
  • South Brisbane, Australia
    • Mater Adult Hospital
  • Westmead, Australia
    • Westmead Hospital
• Austria
  • Graz, Austria
    • University of Graz
  • Innsbruck, Austria
    • Medizinische Universität Innsbruck
  • Salzburg, Austria
    • Uniklinikum Salzburg - Universitätsklinik für Pneumologie/Lungenheilkunde
  • Vienna, Austria
    • Medizinische Universität Wien
  • Wels, Austria
    • Abteilung fuer Pulmologie Klinikum Wels-Grieskirchen
• Belgium
  • Brussel, Belgium
    • Cliniques Universitaires de Bruxelles Hopital Erasme
  • Brussel, Belgium
    • Universitair Ziekenhuis Brussel - Campus Jette
  • Gent, Belgium
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium
    • Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
  • Woluwe-Saint-Lambert, Belgium
    • Cliniques Universitaires Saint-Luc
• Canada
  • Calgary, Canada
    • University of Calgary Medical Clinic of the Foothills Medical Centre
  • Edmonton, Canada
    • Stollery Children's Hospital
  • London, Canada
    • St. Joseph's Health Care London
  • Montreal, Canada
    • Centre Hospitalier de l'Universite de Montreal (CHUM) Hotel-Dieu
  • Montréal, Canada
    • McGill University Health Centre, Glen Site, Montreal Children's Hospital
  • Québec, Canada
    • Institut Universitaire de Cardiologie et Pneumologie de Quebec - Universite Laval
  • Toronto, Canada
    • St. Michael's Hospital
  • Vancouver, Canada
    • British Columbia Children's Hospital
  • Vancouver, Canada
    • St. Paul's Hospital
• Denmark
  • Aarhus, Denmark
    • Aarhus University Hospital
  • Copenhagen, Denmark
    • Juliane Marie Center, Rigshospitalet
• France
  • Bordeaux cedex, France
    • Groupe Hospitaler Pellegrin, CHU De Bordeaux
  • Bron Cedex, France
    • CHU Lyon - Hopital Femme Mere-Enfant
  • Créteil, France
    • Centre Hospitalier Intercommunal Creteil
  • Lille, France
    • Institut Cœur Poumon, CHU de Lille
  • Montpellier Cedex 5, France
    • Hôpital Arnaud de Villeneuve
  • Nantes, France
    • Centre Hospitalier Universitaire De Nantes - G. R. Laennec
  • Nice, France
    • Centre Hospitalier Universitaire (CHU) de Nice - Hopital Pasteur
  • Paris, France
    • Hôpital Robert Debré
  • Paris, France
    • Hôpital Cochin
  • Paris Cedex 15, France
    • Hopital Necker, Enfants Malades
  • Pierre-Bénite, France
    • Centre Hospitalier Lyon Sud
  • Roscoff cedex, France
    • Centre de Perharidy
  • Rouen Cedex, Seine Maritime, France
    • CHU de Rouen - Hôpital Charles Nicolle
  • Strasbourg, France
    • Hôpital de Hautepierre, AX5
  • Suresnes, France
    • Hopital Foch (Suresnes), Hopital Foch, Adultes
  • Tours, France
    • Hôpital Bretonneau
  • Vandoeuvre Les Nancy, France
    • Centre hospitalier universitaire de Nancy, Hôpital de Braboi
• Germany
  • Berlin, Germany
    • Charite Paediatric Pulmonology Department
  • Erlangen, Germany
    • Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital
  • Essen, Germany
    • Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
  • Essen, Germany
    • Universitatsklinikum Essen (AoR), Kinderklinik III, Abt. fur Pneumologie
  • Gießen, Germany
    • Justus-Liebig-Universität Gießen Zentrum für Kinderheilkunde und Jugendmedizin
  • Muenchen, Germany
    • Pneumologisches Studienzentrum Muenchen-West
• Greece
  • Pilea Chortiatis, Greece
    • General Hospital of Thessaloniki "Papanikolaou"
  • Thessaloníki, Greece
    • General Hospital of Thessaloniki 'Hippokratio', 3rd Pediatrics Department of Aristotle University of Thessaloniki
• Hungary
  • Budapest, Hungary
    • National Koranyi Institute for TBC and Pulmonology
  • Torokbalint, Hungary
    • Pulmonology Institute Torokbalint
• Ireland
  • Cork, Ireland
    • Cork University Hospital
  • Dublin, Ireland
    • Children's Health Ireland at Crumlin
  • Dublin, Ireland
    • St. Vincent's University Hospital
  • Dublin, Ireland
    • Children's Health Ireland at Tallaght
  • Dublin, Ireland
    • Children's University Hospital, Dublin
  • Limerick, Ireland
    • University Hospital Limerick (Adults)
  • Limerick, Ireland
    • University Hospital Limerick (Pediatrics)
• Israel
  • Jerusalem, Israel
    • Hadassah Medical Organization
  • Petach Tikvah, Israel
    • Schneider Children's Medical Center of Israel
  • Tel HaShomer, Israel
    • Sheba Medical Center - The Edmond and Lili Safra Children's Hospital
• Italy
  • Ancona, Italy
    • Azienda Ospedaliero Universitaria Ospedale Riuniti
  • Firenze, Italy
    • Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer
  • Genova, Italy
    • IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico
  • Milan, Italy
    • Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
  • Milano, Italy
    • Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico
  • Orbassano, Italy
    • Malattie Apparato Respiratorio 2 - Centro Fibrosi Cistica
  • Potenza, Italy
    • Centro Regionale Fibrosi Cistica, A.O. Ospedale San Carlo
  • Verona, Italy
    • Azienda Ospedaliera di Verona - Ospedale Civile Maggiore
• Netherlands
  • Amsterdam, Netherlands
    • Academisch Medisch Centrum (Academic Medical Centre)
  • Den Haag, Netherlands
    • HagaZiekenhuis van Den Haag
  • Nijmegen, Netherlands
    • UMC St. Radboud
  • Rotterdam, Netherlands
    • Erasmus Medical Center
  • Utrecht, Netherlands
    • University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
• New Zealand
  • Auckland, New Zealand
    • Starship Children's Hospital
  • Auckland, New Zealand
    • Greenlane Clinical Centre
  • Christchurch Hospital, New Zealand
    • Canterbury Respiratory Research Group
  • Hamilton, New Zealand
    • Waikato Hospital
• Norway
  • Bergen, Norway
    • Haukeland Universitetssjukehus (CF)
  • Oslo, Norway
    • Oslo University Hospital, Department of Paediatric Medicine
• Poland
  • Gdańsk, Poland
    • Pediatric Hospital Polanki named of Maciej Płażyński
  • Rabka Zdrój, Poland
    • Institute of Tuberculosis and Lung Diseases
  • Łomianki, Poland
    • Klinika Mukowiscydozy IMD Oddozial Chorob Pluc Szpzoz IM. Dzieci WarszaWY
• Sweden
  • Göteborg, Sweden
    • Sahlgrenska Universitetssjukhuset
  • Malmoe, Sweden
    • Lund University Skanes Universitetssjukhus
  • Stockholm, Sweden
    • Karolinska Universitetssjukhuset, Huddinge
• Switzerland
  • Bern, Switzerland
    • Lindenhofspital - Quartier Bleu
  • Neuchâtel, Switzerland
    • Réseau Hospitalier Neuchâtelois
  • Zürich, Switzerland
    • Kinderspital Zuerich
• United Kingdom
  • Birmingham, United Kingdom
    • Birmingham Children's Hospital
  • Cambridge, United Kingdom
    • Royal Papworth Hospital NHS Foundation Trust
  • Glasgow, United Kingdom
    • Clinical Research Facility, Queen Elizabeth University Hospital
  • Leeds, United Kingdom
    • Leeds General Infirmary
  • Leeds, United Kingdom
    • St. James University Hospital
  • London, United Kingdom
    • Royal Brompton Hospital
  • London, United Kingdom
    • King's College Hospital
  • London, United Kingdom
    • St. Bartholomew's Hospital
  • Manchester, United Kingdom
    • Wythenshawe Hospital
  • Manchester, United Kingdom
    • Royal Manchester Children's Hospital
  • Penarth, United Kingdom
    • All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
  • Southampton, United Kingdom
    • Southampton General Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Banner University of Arizona Medical Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital of Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale New Haven Hospital
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Specialty Care
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary Group, PA
    • Pensacola, Florida, United States, 32514
      • Nemours Children's Specialty Care, Pensacola
    • Saint Petersburg, Florida, United States, 33701
      • Johns Hopkins All Children's Hospital Outpatient Care Center
  • Georgia
    • Atlanta, Georgia, United States, 30324
      • The Emory Clinic at Chantilly
  • Idaho
    • Boise, Idaho, United States, 83702
      • St. Luke's Cystic Fibrosis Center of Idaho
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children at Indiana University Health
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Medical Center
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Partners
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cystic Fibrosis Center Clinical Rsearch Center
    • Worcester, Massachusetts, United States, 01655
      • UMASS Memorial Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5212
      • Michigan Medicine
    • Detroit, Michigan, United States, 48201
      • Harper University Hospital
    • Grand Rapids, Michigan, United States, 49546
      • Spectrum Health Medical Group Adult Cystic Fibrosis Care Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • The Children's Mercy Hospital
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
  • New York
    • Buffalo, New York, United States, 14203
      • CF Therapeutics Development Center of Western New York
    • New Hyde Park, New York, United States, 11040
      • Northwell Health- Long Island Jewish Medical Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27104
      • Wake Forest Baptist Health
  • Ohio
    • Akron, Ohio, United States, 44308
      • Akron Children's Hospital
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
    • Dayton, Ohio, United States, 45404
      • Dayton Children's Hospital
    • Toledo, Ohio, United States, 43606
      • ProMedica Toledo Hospital/Toledo Children's Hospital/Pediatric Pulmonary & Cystic Fibrosis Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Oklahoma City, Oklahoma, United States, 73112
      • Santiago Reyes, M.D.
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Prisma Health Richland Campus
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Sanford Children's Speciality Clinic
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390-8558
      • The University of Texas Southwestern Medical Center
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Health Care System
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah - Primary Children's Medical Center
  • Vermont
    • Colchester, Vermont, United States, 05446
      • Vermont Lung Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Spokane, Washington, United States, 99204
      • Providence Pediatric Pulmonary & Cystic Fibrosis Clinic
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University Hospital and UW Health Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VX-121/TEZ/D-IVA; Participants will receive VX-121/TEZ/D-IVA in the morning.	Drug: VX-121/TEZ/D-IVA; Fixed-dose combination tablets for oral administration.; Other Names: VX-121/VX-661/CTP-656; VX-121/VX-661/VX-561; VX-121/tezacaftor/deutivacaftor; Drug: Placebo (matched to ELX/TEZ/IVA); Placebo matched to ELX/TEZ/IVA for oral administration.; Drug: Placebo (matched to IVA); Placebo matched to IVA for oral administration.
Active Comparator: ELX/TEZ/IVA; Participants will receive ELX/TEZ/IVA in the morning and IVA in the evening.	Drug: IVA; Tablet for oral administration.; Other Names: VX-770; ivacaftor; Drug: ELX/TEZ/IVA; Fixed-dose combination tablets for oral administration.; Other Names: VX-445/VX-661/VX-770; elexacaftor/tezacaftor/ivacaftor; Drug: Placebo (matched to VX-121/TEZ/D-IVA); Placebo matched to VX-121/TEZ/D-IVA for oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24	From Baseline Through Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Absolute Change From Baseline in Sweat Chloride (SwCl) Through Week 24	From Baseline Through Week 24
Proportion of Participants With SwCl <60 Millimole per Liter (mmol/L) Through Week 24 (Pooled With Data From Study VX20-121-102)	From Baseline Through Week 24
Proportion of Participants With SwCl <30 mmol/L Through Week 24 (Pooled With Data From Study VX20-121-102)	From Baseline Through Week 24

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2021
• Primary Completion (Actual): May 18, 2023
• Study Completion (Actual): November 30, 2023

Study Registration Dates

• First Submitted: September 29, 2021
• First Submitted That Met QC Criteria: September 29, 2021
• First Posted (Actual): October 13, 2021

Study Record Updates

• Last Update Posted (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Ivacaftor; Elexacaftor
• Other Study ID Numbers: VX20-121-103; 2021-000694-85 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No