A Phase 3 Study of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
2 other identifiers
interventional
405
12 countries
110
Brief Summary
This study will evaluate the efficacy of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a minimal function mutation (F/MF subjects).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jun 2018
Shorter than P25 for phase_3
110 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 2, 2018
CompletedFirst Posted
Study publicly available on registry
May 15, 2018
CompletedStudy Start
First participant enrolled
June 15, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 24, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
April 24, 2019
CompletedResults Posted
Study results publicly available
May 19, 2020
CompletedMay 19, 2020
May 1, 2020
10 months
May 2, 2018
April 22, 2020
May 6, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline at Week 4
Secondary Outcomes (12)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
From Baseline through Week 24
Number of Pulmonary Exacerbations (PEx)
From Baseline through Week 24
Absolute Change in Sweat Chloride (SwCl)
From Baseline through Week 24
Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score
From Baseline through Week 24
Absolute Change in Body Mass Index (BMI)
From Baseline at Week 24
- +7 more secondary outcomes
Study Arms (2)
Placebo
PLACEBO COMPARATORParticipants who received placebo matched to VX-445/TEZ/IVA for 24 weeks in the TC treatment period.
VX-445/TEZ/IVA TC
EXPERIMENTALParticipants who received VX-445 200 mg/TEZ 100 mg/IVA150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 weeks in the TC treatment period.
Interventions
Participants received VX-445/TEZ/IVA orally once daily in the morning.
Participants received IVA orally once daily in the evening
Participants received placebo matched VX-445/TEZ/IVA orally once daily in the morning and placebo matched to IVA orally once daily in the evening.
Eligibility Criteria
You may qualify if:
- Heterozygous for the F508del mutation (F/MF)
- Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height
You may not qualify if:
- Clinically significant cirrhosis with or without portal hypertension
- Lung infection with organisms associated with a more rapid decline in pulmonary status
- Solid organ or hematological transplantation
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (115)
Banner University of Arizona Medical Center
Tucson, Arizona, 85724, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205, United States
Miller Children's Hospital/ Long Beach Memorial
Long Beach, California, 90806, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Valley Children's Hospital/ Children's Hospital of Central California
Madera, California, 93636, United States
Kaiser Permanente
Oakland, California, 94611, United States
University of California Davis Medical Center
Sacramento, California, 95817, United States
UCSF Gateway Medical Center
San Francisco, California, 94143, United States
National Jewish Health
Denver, Colorado, 80206, United States
University of Florida, Shands Hospital
Gainesville, Florida, 32610, United States
Joe DiMaggio Cystic Fibrosis & Pulmonary Center/ Joe DiMaggio Children's Hospital/ Memorial Regional Hospital
Hollywood, Florida, 33021, United States
Nemours Children's Specialty Care
Jacksonville, Florida, 32207, United States
Central Florida Pulmonary Group
Orlando, Florida, 32803, United States
Nemours Children's Hospital
Orlando, Florida, 32827, United States
Tampa General Hospital Cardiac and Lung Transplant Clinic
Tampa, Florida, 33606, United States
Children's Speciality Services at North Druid Hills
Atlanta, Georgia, 30324, United States
Augusta University
Augusta, Georgia, 30912, United States
Ann & Robert Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611, United States
Northwestern Memorial Hospital
Chicago, Illinois, 60611, United States
Saint Francis Medical Center/ Children's Hospital of Illinois/OSF
Peoria, Illinois, 61637, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
Tulane Medical Center
New Orleans, Louisiana, 70112, United States
Maine Medical Partners
Portland, Maine, 04102, United States
Massachusetts General Hospital Cystic Fibrosis Center
Boston, Massachusetts, 02114, United States
Harper University Hospital
Detroit, Michigan, 48201, United States
Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota
Minneapolis, Minnesota, 55404, United States
Billings Clinic
Billings, Montana, 59101, United States
Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Morristown Medical Center
Morristown, New Jersey, 07960, United States
University of New Mexico Clinical & Translational Science Center
Albuquerque, New Mexico, 87131, United States
Mount Sinai Beth Israel
New York, New York, 10003, United States
New York Medical College
Valhalla, New York, 10595, United States
UNC Marsico Clinical Research Center
Chapel Hill, North Carolina, 27517, United States
Akron Children's Hospital
Akron, Ohio, 44308, United States
UC Health Holmes
Cincinnati, Ohio, 45220, United States
University Hospitals Cleveland Medical Center/ Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Dayton Children's Hospital
Dayton, Ohio, 45404, United States
ProMedica Toledo Hospital/ Toledo Children's Hospital/ Pediatric Pulmonary & Cystic Fibrosis Center
Toledo, Ohio, 43606, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Austin Children's Chest Associates
Austin, Texas, 78723, United States
The University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
The University of Texas Health Science Center at Tyler
Tyler, Texas, 75708, United States
Vermont Lung Center
Colchester, Vermont, 05446, United States
University of Virginia Primary Care Center
Charlottesville, Virginia, 22908, United States
Children's Hospital of the King's Daughters
Norfolk, Virginia, 23507, United States
Children's Hospital of Richmond at VCU, Children's Pavilion
Richmond, Virginia, 23298, United States
University of Washington Medical Center
Seattle, Washington, 98195, United States
West Virginia University
Morgantown, West Virginia, 26506, United States
University of Wisconsin Hospitals and Clinics
Madison, Wisconsin, 53792, United States
CTSI Adult Translational Research Unit/Medical College of Wisconsin/Froedtert Hospital
Milwaukee, Wisconsin, 53226, United States
Women & Children's Hospital
North Adelaide, Australia
The Royal Children's Hospital
Parkville, Australia
Mater Adult Hospital
South Brisbane, Australia
The Children's Hospital at Westmead
Westmead, Australia
Westmead Hospital
Westmead, Australia
University of Graz
Graz, Austria
Medizinische Universitat Innsbruck
Innsbruck, Austria
LKH - Universitätsklinikum der PMU Salzburg
Salzburg, Austria
Medizinische Universitat Wien
Vienna, Austria
Cliniques Universitaires de Bruxelles Hopital Erasme
Brussels, Belgium
Universitair Ziekenhuis Brussel - Campus Jette
Brussels, Belgium
UZ Antwerpen
Edegem, Belgium
Universitair Ziekenhuis Gent
Ghent, Belgium
Universitaire Ziekenhuizen Leuven - Campus Gathuisberg
Leuven, Belgium
British Columbia's Children's Hospital
Vancouver, British Columbia, Canada
St. Paul's Hospital
Vancouver, British Columbia, Canada
McGill University Health Centre, Glen Site, Montreal Children's Hospital
Montreal, Quebec, Canada
University of Calgary Medical Clinic of the Foothills Medical Centre
Calgary, Canada
Centre Hospitalier De L'Universite Laval
Qubec, Canada
Saint John Regional Hospital
Saint John, Canada
The Hospital for Sick Children
Toronto, Canada
Vancouver Island Health Authority
Victoria, Canada
Fakultni Nemocnice Brno
Brno, Czechia
Fakultni nemocnice v Motole
Prague, Czechia
Centre Hospitalier Lyon Sud
Benite Cedex, France
Groupe Hospitaler Pellegrin, CHU De Bordeaux
Bordeaux, France
CHU Marseille - Hopital Nord
Marseille, France
CHU de Nice - Hopital Pasteur
Nice, France
Hopital Cochin
Paris, France
CHU de Rouen - Hopital Charles Nicolle
Rouen Cedex, Seine Maritime, France
Hopital Foch (Suresnes), Hopital Foch, Adultes
Suresnes, France
Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital
Erlangen, Germany
Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin
Giessen, Germany
Hannover Medical School
Hanover, Germany
Heidelberg Cystic Fibrosis Center
Heidelberg, Germany
Johannes Gutenberg-Universitaet
Mainz, Germany
Dr. von Haunersches Kinderspital
München, Germany
Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin
Tübingen, Germany
University Hospital Wuerzburg
Würzburg, Germany
General Hospital of Attika "Sismanoglio"(Adult CF center, NHS)
Marousi, Greece
Azienda Ospedaliero Universitaria Ospedale Riuniti
Ancona, Italy
Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer
Florence, Italy
IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico
Genova, Italy
Azienda Ospedaliera Universitaria Policlinico G. Martino
Messina, Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, Italy
Centro Regionale Fibrosi Cistica, A.O. Ospedale San Carlo
Potenza, Italy
Azienda Ospedaliera di Verona-Ospedale Civile Maggiore
Verona, Italy
Academic Medical Center
Amsterdam, Netherlands
University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
Heidelberglaan, Netherlands
UMC St. Radboud
Nijmegen, Netherlands
Erasmus Medical Center
Rotterdam, Netherlands
HagaZiekenhuis van den Haag
The Hague, Netherlands
Karolinska Univeritetssjukhuset, Huddinge
Stockholm, Sweden
The Royal Belfast Hospital for Sick Children
Belfast, United Kingdom
Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
Brimingham, United Kingdom
Royal Hospital for Sick Children
Edinburgh, United Kingdom
Western General Hospital
Edinburgh, United Kingdom
Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
Exeter, United Kingdom
Leeds General Infirmary
Leeds, United Kingdom
King's College Hospital
London, United Kingdom
Royal Manchester Children's Hospital
Manchester, United Kingdom
Southampton General Hospital
Southampton, United Kingdom
Related Publications (2)
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.
PMID: 37983082DERIVEDMiddleton PG, Mall MA, Drevinek P, Lands LC, McKone EF, Polineni D, Ramsey BW, Taylor-Cousar JL, Tullis E, Vermeulen F, Marigowda G, McKee CM, Moskowitz SM, Nair N, Savage J, Simard C, Tian S, Waltz D, Xuan F, Rowe SM, Jain R; VX17-445-102 Study Group. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019 Nov 7;381(19):1809-1819. doi: 10.1056/NEJMoa1908639. Epub 2019 Oct 31.
PMID: 31697873DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Monitor
- Organization
- Vertex Pharmaceuticals Incorporated
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 2, 2018
First Posted
May 15, 2018
Study Start
June 15, 2018
Primary Completion
April 24, 2019
Study Completion
April 24, 2019
Last Updated
May 19, 2020
Results First Posted
May 19, 2020
Record last verified: 2020-05