A Phase 3 Study of VX-121 Combination Therapy in Participants With Cystic Fibrosis (CF) Heterozygous for F508del and a Minimal Function Mutation (F/MF)

Vertex Pharmaceuticals Incorporated (Industry)
Overall Status
CT.gov ID

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 heterozygous for F508del and a minimal function mutation (F/MF participants).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Anticipated Enrollment :
400 participants
Intervention Model:
Parallel Assignment
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
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 (CF) Who Are Heterozygous for F508del and a Minimal Function Mutation (F/MF)
Actual Study Start Date :
Sep 14, 2021
Anticipated Primary Completion Date :
Jun 1, 2023
Anticipated Study Completion Date :
Jan 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 VX20-121-103) [From Baseline Through Week 24]

    3. Proportion of Participants With SwCl <30 mmol/L Through Week 24 (Pooled With Data From Study VX20-121-103) [From Baseline Through Week 24]

    Eligibility Criteria


    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    Accepts Healthy Volunteers:
    Key Inclusion Criteria:
    • Heterozygous for F508del and a minimal function mutation (F/MF genotype)

    • Forced expiratory volume in 1 second (FEV1) value >=40% and <=90% of predicted mean for age, sex, and height for participants currently receiving ELX/TEZ/IVA therapy; FEV1 >=40% and <=80% for participants not currently receiving ELX/TEZ/IVA

    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


    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 Arkansas Children's Hospital Little Rock Arkansas United States 72202
    4 Miller Children's Hospital / Long Beach Memorial Long Beach California United States 90806
    5 Children's Hospital Los Angeles Los Angeles California United States 90027
    6 Kaiser Permanente Oakland California United States 94611
    7 University of California Davis Medical Center Sacramento California United States 95817
    8 University of California San Francisco, Lung Transplant Program San Francisco California United States 94143
    9 Children's Hospital of Colorado Aurora Colorado United States 80045
    10 National Jewish Health Denver Colorado United States 80206
    11 University of Florida, Shands Hospital Gainesville Florida United States 32610
    12 Joe DiMaggio Cystic Fibrosis & Pulmonary Center Hollywood Florida United States 33021
    13 Central Florida Pulmonary Group, PA Orlando Florida United States 32803
    14 Nemours Children's Hospital Orlando Florida United States 32827
    15 Johns Hopkins All Children's Hospital Outpatient Care Center Saint Petersburg Florida United States 33701
    16 The Emory Clinic at Chantilly Atlanta Georgia United States 30324
    17 Augusta University Augusta Georgia United States 30912
    18 St. Luke's Cystic Fibrosis Center of Idaho Boise Idaho United States 83702
    19 Ann & Robert H. Lurie Children's Hospital of Chicago Chicago Illinois United States 60611
    20 Northwestern Memorial Hospital Chicago Illinois United States 60611
    21 Indiana University Indianapolis Indiana United States 46202
    22 Riley Hospital for Children at Indiana University Health Indianapolis Indiana United States 46202
    23 University of Kansas Medical Center Kansas City Kansas United States 66160
    24 Tulane Medical Center New Orleans Louisiana United States 70112
    25 Massachusetts General Hospital Cystic Fibrosis Center Clinical Rsearch Center Boston Massachusetts United States 02114
    26 Boston Children's Hospital Boston Massachusetts United States 02115
    27 UMass Memorial Medical Center Worcester Massachusetts United States 01655
    28 Michigan Medicine Ann Arbor Michigan United States 48109-5212
    29 Helen DeVos Children's Hospital CF Center Grand Rapids Michigan United States 49503
    30 University of Minnesota Minneapolis Minnesota United States 55455
    31 University of Mississippi Medical Center Jackson Mississippi United States 39216
    32 Childrens Hospital University of Missouri Health Sciences Center Columbia Missouri United States 65212
    33 The Children's Mercy Hospital Kansas City Missouri United States 64108
    34 Cardinal Glennon Children's Hospital - St. Louis University Saint Louis Missouri United States 63104
    35 Washington University School of Medicine / St. Louis Children's Hospital Saint Louis Missouri United States 63110
    36 Billings Clinic Billings Montana United States 59101
    37 Nebraska Medical Center Omaha Nebraska United States 68198
    38 Dartmouth Hitchcock, Manchester Manchester New Hampshire United States 03104
    39 Morristown Medical Center Morristown New Jersey United States 07960
    40 Albany Medical College Albany New York United States 12208
    41 CF Therapeutics Development Center of Western New York Buffalo New York United States 14203
    42 Northwell Health- Long Island Jewish Medical Center New Hyde Park New York United States 11040
    43 Columbia University Medical Center New York New York United States 10032
    44 New York Medical College Valhalla New York United States 10595
    45 Atrium Health Levine Children's Hospital Charlotte North Carolina United States 28203
    46 Wake Forest Baptist Health Winston-Salem North Carolina United States 27104
    47 Cleveland Clinic CF Cleveland Ohio United States 44195
    48 Nationwide Children's Hospital Columbus Ohio United States 43205
    49 Dayton Children's Hospital Dayton Ohio United States 45404
    50 Oregon Health & Science University Portland Oregon United States 97239
    51 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    52 UPMC Children's Hospital of Pittsburgh Pittsburgh Pennsylvania United States 15224
    53 Sanford Children's Speciality Clinic Sioux Falls South Dakota United States 57105
    54 University of Tennessee Medical Center Knoxville Tennessee United States 37920
    55 Children's Foundation Research Center / Le Bonheur Children's Hospital Memphis Tennessee United States 38105
    56 Vanderbilt University Medical Center Nashville Tennessee United States 37232
    57 Driscoll Children's Hospital Corpus Christi Texas United States 78411
    58 The University of Texas Southwestern Medical Center Dallas Texas United States 75390-8558
    59 Cook Children's Health Care System Fort Worth Texas United States 76104
    60 Texas Children's Hospital - Baylor College of Medicine Houston Texas United States 77030
    61 University of Utah - Primary Children's Medical Center Salt Lake City Utah United States 84132
    62 Vermont Lung Center Colchester Vermont United States 05446
    63 University of Virginia Health System Charlottesville Virginia United States 22908
    64 Inova Fairfax Falls Church Virginia United States 22042
    65 University of Washington Medical Center Seattle Washington United States 98195
    66 University of Wisconsin Hospital and Clinics Madison Wisconsin United States 53792
    67 Royal Prince Alfred Hospital Camperdown Australia
    68 The Prince Charles Hospital Chermside Australia
    69 Alfred Hospital Melbourne, VIC Australia
    70 Mater Adult Hospital South Brisbane Australia
    71 Queensland Children's Hospital South Brisbane Australia
    72 Westmead Hospital Westmead Australia
    73 Klinika Detskych Infekcnich Nemoci Brno Czechia
    74 Fakultni nemocnice v Motole Praha 5 Czechia
    75 Charite Paediatric Pulmonology Department Berlin Germany
    76 St. Josef-Hospital Bochum Germany
    77 Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen Essen Germany
    78 Universitatsklinikum Essen (AoR), Kinderklinik III, Abt. fur Pneumologie Essen Germany
    79 Johann Wolfgang Goethe University Frankfurt Germany
    80 Hannover Medical School Hannover Germany
    81 Medizinische Hochschule Hannover Hannover Germany
    82 Mukoviszidose-Zentrum am Universitätsklinikum Jena, Klinik für Kinder- und Jugendmedizin Jena Germany
    83 Johannes Gutenberg-Universitaet Mainz Germany
    84 Pneumologisches Studienzentrum Muenchen-West Muenchen Germany
    85 Klinikum Innenstadt, University of Munich München Germany
    86 Klinikum Westbrandenburg (CF) Potsdam Germany
    87 Universitätsklinikum Würzburg Würzburg Germany
    88 Cork University Hospital Cork Ireland
    89 Children's Health Ireland at Crumlin Dublin Ireland
    90 Children's Health Ireland at Tallaght Dublin Ireland
    91 Children's Health Ireland at Temple Street Dublin Ireland
    92 St. Vincent's University Hospital Dublin Ireland
    93 University Hospital Limerick (Adults) Limerick Ireland
    94 University Hospital Limerick (Pediatrics) Limerick Ireland
    95 Hadassah University Hospital Mount Scopus Jerusalem Israel
    96 Schneider Children's Medical Center of Israel Petach Tikvah Israel
    97 Sheba Medical Center - The Edmond and Lili Safra Children's Hospital Tel HaShomer Israel
    98 Greenlane Clinical Centre Auckland New Zealand
    99 Starship Children's Hospital Auckland New Zealand
    100 Canterbury Respiratory Research Group Christchurch Hospital New Zealand
    101 Waikato Hospital Hamilton New Zealand
    102 Hospital de Santa Maria Lisbon Portugal
    103 Hospital Sao Joao Porto Portugal
    104 Hospital Saint Joan de Deu Barcelona Spain
    105 Hospital Universitari Vall d Hebron Barcelona Spain
    106 Hospital Universitario 12 de Octubre Madrid Spain
    107 Hospital Universitario Ramon y Cajal Madrid Spain
    108 Hospital Virgen de la Arrixaca Murcia Spain
    109 Corporacio Sanitaria Parc Tauli - Sabadell Hospital Universitari Sabadell Spain
    110 Hospital Universitario Virgen del Rocio Sevilla Spain
    111 Hospital Universitario y Politecnico La Fe Valencia Spain
    112 Sahlgrenska Universitetssjukhuset Göteborg Sweden
    113 Lund University Skanes Universitetssjukhus Malmoe Sweden
    114 Karolinska Universitetssjukhuset, Huddinge Stockholm Sweden
    115 Birmingham Heartlands Hospital Birmingham United Kingdom
    116 University Hospitals Bristol and Weston NHS Foundation Trust, Bristol Royal Hospital Bristol United Kingdom
    117 Royal Papworth Hospital NHS Foundation Trust Cambridge United Kingdom
    118 Royal Hospital for Sick Children Edinburgh United Kingdom
    119 Western General Hospital Edinburgh United Kingdom
    120 Royal Devon and Exeter Hospital Exeter United Kingdom
    121 Clinical Research Facility, Queen Elizabeth University Hospital Glasgow United Kingdom
    122 St. James University Hospital Leeds United Kingdom
    123 King's College Hospital London United Kingdom
    124 Royal Brompton Hospital London United Kingdom
    125 St. Bartholomew's Hospital London United Kingdom
    126 Wythenshawe Hospital Manchester United Kingdom
    127 Clinical Research Facility Newcastle Upon Tyne United Kingdom
    128 All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough Penarth United Kingdom
    129 Southampton General Hospital Southampton United Kingdom

    Sponsors and Collaborators

    • Vertex Pharmaceuticals Incorporated


    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information


    None provided.
    Responsible Party:
    Vertex Pharmaceuticals Incorporated
    ClinicalTrials.gov Identifier:
    Other Study ID Numbers:
    • VX20-121-102
    • 2021-000712-31
    First Posted:
    Sep 2, 2021
    Last Update Posted:
    Aug 25, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Plan to Share IPD:
    Studies a U.S. FDA-regulated Drug Product:
    Studies a U.S. FDA-regulated Device Product:
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 25, 2022