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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

Sponsor
Vertex Pharmaceuticals Incorporated (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05076149
Collaborator
(none)
550
Enrollment
153
Locations
2
Arms
27.2
Anticipated Duration (Months)
3.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
550 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Oct 27, 2021
Anticipated Primary Completion Date :
Jul 1, 2023
Anticipated Study Completion Date :
Feb 1, 2024

Arms and Interventions

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: ELX/TEZ/IVA
    Fixed-dose combination tablets for oral administration.
    Other Names:
  • VX-445/VX-661/VX-770
  • elexacaftor/tezacaftor/ivacaftor

    • Drug: IVA
    Tablet for oral administration.
    Other Names:
  • VX-770
  • ivacaftor

    • Drug: Placebo (matched to VX-121/TEZ/D-IVA)
    Placebo matched to VX-121/TEZ/D-IVA for oral administration.

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. Absolute Change From Baseline in Sweat Chloride (SwCl) Through Week 24 [From Baseline Through Week 24]

    2. 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]

    3. Proportion of Participants With SwCl <30 mmol/L Through Week 24 (Pooled With Data From Study VX20-121-102) [From Baseline Through Week 24]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35233
    2 Banner University of Arizona Medical Center Tucson Arizona United States 85724
    3 University of Arkansas for Medical Sciences Little Rock Arkansas United States 72205
    4 Children's Hospital Los Angeles Los Angeles California United States 90027
    5 Children's Hospital of Orange County Orange California United States 92868
    6 University of California Davis Medical Center Sacramento California United States 95817
    7 Children's Hospital of Colorado Aurora Colorado United States 80045
    8 National Jewish Health Denver Colorado United States 80206
    9 Yale New Haven Hospital New Haven Connecticut United States 06510
    10 Nemours Children's Specialty Care Jacksonville Florida United States 32207
    11 University of Miami Miller School of Medicine Miami Florida United States 33136
    12 Central Florida Pulmonary Group, PA Orlando Florida United States 32803
    13 Nemours Children's Specialty Care, Pensacola Pensacola Florida United States 32514
    14 Johns Hopkins All Children's Hospital Outpatient Care Center Saint Petersburg Florida United States 33701
    15 The Emory Clinic at Chantilly Atlanta Georgia United States 30324
    16 St. Luke's Cystic Fibrosis Center of Idaho Boise Idaho United States 83702
    17 Northwestern Memorial Hospital Chicago Illinois United States 60611
    18 Indiana University Indianapolis Indiana United States 46202
    19 Riley Hospital for Children at Indiana University Health Indianapolis Indiana United States 46202
    20 University of Kentucky Lexington Kentucky United States 40536
    21 Tulane Medical Center New Orleans Louisiana United States 70112
    22 Maine Medical Partners Portland Maine United States 04102
    23 Massachusetts General Hospital Cystic Fibrosis Center Clinical Rsearch Center Boston Massachusetts United States 02114
    24 Boston Children's Hospital Boston Massachusetts United States 02115
    25 UMass Memorial Medical Center Worcester Massachusetts United States 01655
    26 Michigan Medicine Ann Arbor Michigan United States 48109-5212
    27 Harper University Hospital Detroit Michigan United States 48201
    28 Spectrum Health Medical Group Adult Cystic Fibrosis Care Center Grand Rapids Michigan United States 49546
    29 University of Mississippi Medical Center Jackson Mississippi United States 39216
    30 The Children's Mercy Hospital Kansas City Missouri United States 64108
    31 Washington University School of Medicine Saint Louis Missouri United States 63110
    32 Billings Clinic Billings Montana United States 59101
    33 Morristown Medical Center Morristown New Jersey United States 07960
    34 CF Therapeutics Development Center of Western New York Buffalo New York United States 14203
    35 Northwell Health- Long Island Jewish Medical Center New Hyde Park New York United States 11040
    36 Columbia University Medical Center New York New York United States 10032
    37 SUNY Upstate Medical University Syracuse New York United States 13210
    38 Wake Forest Baptist Health Winston-Salem North Carolina United States 27104
    39 Akron Children's Hospital Akron Ohio United States 44308
    40 Nationwide Children's Hospital Columbus Ohio United States 43205
    41 Dayton Children's Hospital Dayton Ohio United States 45404
    42 ProMedica Toledo Hospital/Toledo Children's Hospital/Pediatric Pulmonary & Cystic Fibrosis Center Toledo Ohio United States 43606
    43 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    44 Santiago Reyes, M.D. Oklahoma City Oklahoma United States 73112
    45 Oregon Health & Science University Portland Oregon United States 97239
    46 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    47 UPMC Children's Hospital of Pittsburgh Pittsburgh Pennsylvania United States 15224
    48 Prisma Health Richland Campus Columbia South Carolina United States 29203
    49 Sanford Children's Speciality Clinic Sioux Falls South Dakota United States 57105
    50 University of Tennessee Medical Center Knoxville Tennessee United States 37920
    51 Vanderbilt University Medical Center Nashville Tennessee United States 37232
    52 The University of Texas Southwestern Medical Center Dallas Texas United States 75390-8558
    53 Cook Children's Health Care System Fort Worth Texas United States 76104
    54 University of Utah - Primary Children's Medical Center Salt Lake City Utah United States 84132
    55 Vermont Lung Center Colchester Vermont United States 05446
    56 University of Virginia Health System Charlottesville Virginia United States 22908
    57 Children's Hospital of the King's Daughters Norfolk Virginia United States 23507
    58 Providence Pediatric Pulmonary & Cystic Fibrosis Clinic Spokane Washington United States 99204
    59 West Virginia University Morgantown West Virginia United States 26506
    60 University Hospital and UW Health Clinics Madison Wisconsin United States 53792
    61 Royal Prince Alfred Hospital Camperdown Australia
    62 The Prince Charles Hospital Chermside Australia
    63 Alfred Hospital Melbourne, VIC Australia
    64 Institute for Respiratory Health Nedlands Australia
    65 Telethon Kids Institute Nedlands Australia
    66 The Royal Children's Hospital Parkville, VIC Australia
    67 Mater Adult Hospital South Brisbane Australia
    68 Queensland Children's Hospital South Brisbane Australia
    69 Westmead Hospital Westmead Australia
    70 University of Graz Graz Austria
    71 Medizinische Universität Innsbruck Innsbruck Austria
    72 Cliniques Universitaires de Bruxelles Hopital Erasme Brussel Belgium
    73 Universitair Ziekenhuis Brussel - Campus Jette Brussel Belgium
    74 Universitair Ziekenhuis Gent Gent Belgium
    75 Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg Leuven Belgium
    76 Cliniques Universitaires Saint-Luc Woluwe-Saint-Lambert Belgium
    77 University of Calgary Medical Clinic of the Foothills Medical Centre Calgary Canada
    78 Stollery Children's Hospital Edmonton Canada
    79 Centre Hospitalier de l'Universite de Montreal (CHUM) Hotel-Dieu Montreal Canada
    80 McGill University Health Centre, Glen Site, Montreal Children's Hospital Montréal Canada
    81 Institut Universitaire de Cardiologie et Pneumologie de Quebec - Universite Laval Québec Canada
    82 St. Michael's Hospital Toronto Canada
    83 British Columbia Children's Hospital Vancouver Canada
    84 St. Paul's Hospital Vancouver Canada
    85 Aarhus University Hospital Aarhus Denmark
    86 Juliane Marie Center, Rigshospitalet Copenhagen Denmark
    87 Groupe Hospitaler Pellegrin, CHU De Bordeaux Bordeaux cedex France
    88 CHU Lyon - Hopital Femme Mere-Enfant Bron Cedex France
    89 Centre Hospitalier Intercommunal Creteil Créteil France
    90 Institut Cœur Poumon, CHU de Lille Lille France
    91 Hopital Arnaud de Villeneuve Montpellier Cedex 5 France
    92 Centre Hospitalier Universitaire De Nantes - G. R. Laennec Nantes France
    93 Centre Hospitalier Universitaire (CHU) de Nice - Hopital Pasteur Nice France
    94 Hopital Necker, Enfants Malades Paris Cedex 15 France
    95 Hopital Cochin Paris France
    96 Hopital Robert Debre Paris France
    97 Centre Hospitalier Lyon Sud Pierre-Bénite France
    98 Centre de Perharidy Roscoff cedex France
    99 CHU de Rouen - Hopital Charles Nicolle Rouen Cedex, Seine Maritime France
    100 Hôpital de Hautepierre, AX5 Strasbourg France
    101 Hopital Foch (Suresnes), Hopital Foch, Adultes Suresnes France
    102 Hopital Bretonneau Tours France
    103 Centre hospitalier universitaire de Nancy, Hôpital de Braboi Vandoeuvre Les Nancy France
    104 Charite Paediatric Pulmonology Department Berlin Germany
    105 Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen Essen Germany
    106 Justus-Liebig-Universität Gießen Zentrum für Kinderheilkunde und Jugendmedizin Gießen Germany
    107 Pneumologisches Studienzentrum Muenchen-West Muenchen Germany
    108 General Hospital of Thessaloniki "Papanikolaou" Pilea Chortiatis Greece
    109 General Hospital of Thessaloniki 'Hippokratio', 3rd Pediatrics Department of Aristotle University of Thessaloniki Thessaloníki Greece
    110 Cork University Hospital Cork Ireland
    111 Children's Health Ireland at Crumlin Dublin Ireland
    112 Children's Health Ireland at Tallaght Dublin Ireland
    113 Children's University Hospital, Dublin Dublin Ireland
    114 St. Vincent's University Hospital Dublin Ireland
    115 University Hospital Limerick (Adults) Limerick Ireland
    116 University Hospital Limerick (Pediatrics) Limerick Ireland
    117 Hadassah Medical Organization Jerusalem Israel
    118 Schneider Children's Medical Center of Israel Petach Tikvah Israel
    119 Sheba Medical Center - The Edmond and Lili Safra Children's Hospital Tel HaShomer Israel
    120 Azienda Ospedaliero Universitaria Ospedale Riuniti Ancona Italy
    121 Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer Firenze Italy
    122 IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico Genova Italy
    123 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano Italy
    124 Malattie Apparato Respiratorio 2 - Centro Fibrosi Cistica Orbassano Italy
    125 Azienda Ospedaliera di Verona - Ospedale Civile Maggiore Verona Italy
    126 Academisch Medisch Centrum (Academic Medical Centre) Amsterdam Netherlands
    127 HagaZiekenhuis van den Haag Den Haag Netherlands
    128 UMC St. Radboud Nijmegen Netherlands
    129 Erasmus Medical Center Rotterdam Netherlands
    130 University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis Utrecht Netherlands
    131 Greenlane Clinical Centre Auckland New Zealand
    132 Starship Children's Hospital Auckland New Zealand
    133 Canterbury Respiratory Research Group Christchurch Hospital New Zealand
    134 Waikato Hospital Hamilton New Zealand
    135 Haukeland Universitetssjukehus (CF) Bergen Norway
    136 Institute of Tuberculosis and Lung Diseases Rabka Zdrój Poland
    137 Sahlgrenska Universitetssjukhuset Göteborg Sweden
    138 Lund University Skanes Universitetssjukhus Malmoe Sweden
    139 Karolinska Universitetssjukhuset, Huddinge Stockholm Sweden
    140 Lindenhofspital - Quartier Bleu Bern Switzerland
    141 Réseau Hospitalier Neuchâtelois Neuchâtel Switzerland
    142 Kinderspital Zuerich Zürich Switzerland
    143 Birmingham Children's Hospital Birmingham United Kingdom
    144 Royal Papworth Hospital NHS Foundation Trust Cambridge United Kingdom
    145 Clinical Research Facility, Queen Elizabeth University Hospital Glasgow United Kingdom
    146 Leeds General Infirmary Leeds United Kingdom
    147 St. James University Hospital Leeds United Kingdom
    148 King's College Hospital London United Kingdom
    149 St. Bartholomew's Hospital London United Kingdom
    150 Royal Manchester Children's Hospital Manchester United Kingdom
    151 Wythenshawe Hospital Manchester United Kingdom
    152 All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough Penarth United Kingdom
    153 Southampton General Hospital Southampton United Kingdom

    Sponsors and Collaborators

    • Vertex Pharmaceuticals Incorporated

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Vertex Pharmaceuticals Incorporated
    ClinicalTrials.gov Identifier:
    NCT05076149
    Other Study ID Numbers:
    • VX20-121-103
    • 2021-000694-85
    First Posted:
    Oct 13, 2021
    Last Update Posted:
    Aug 24, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Cystic Fibrosis
    Fibrosis
    Ivacaftor
    Elexacaftor

    Study Results

    No Results Posted as of Aug 24, 2022