A Study of VX-445 Combination Therapy in CF Subjects Homozygous for F508del (F/F)
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 Homozygous for the F508del Mutation (F/F)
2 other identifiers
interventional
113
4 countries
44
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 homozygous for the F508del mutation (F/F)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Aug 2018
Shorter than P25 for phase_3
44 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
August 3, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 28, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
December 28, 2018
CompletedResults Posted
Study results publicly available
January 27, 2020
CompletedJanuary 27, 2020
January 1, 2020
5 months
May 2, 2018
December 20, 2019
January 24, 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 (4)
Absolute Change in Sweat Chloride (SwCl)
From Baseline at Week 4
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
From Baseline at Week 4
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA
Day 1 and Week 4
Study Arms (2)
TEZ/IVA
ACTIVE COMPARATORFollowing a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period.
VX-445/TEZ/IVA TC
EXPERIMENTALFollowing a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
Interventions
Participants received VX-445/TEZ/IVA orally once daily in the morning.
Participants received TEZ/IVA orally once daily in the morning.
Participants received IVA orally once daily in the evening.
Participants received placebo matched to VX-445/TEZ/IVA orally once daily in the morning.
Eligibility Criteria
You may qualify if:
- Homozygous for the F508del mutation (F/F)
- 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 (44)
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
Madera, California, 93636, United States
National Jewish Health
Denver, Colorado, 80206, United States
Joe DiMaggio Cystic Fibrosis & Pulmonary Center/ Joe DiMaggio Children's Hospital/ Memorial Regional Hospital
Hollywood, Florida, 33021, United States
Central Florida Pulmonary Group, PA
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
Northwestern Memorial Hospital
Chicago, Illinois, 60611, United States
Saint Francis Medical Center/ Children's Hospital of Illinoise/OSF
Peoria, Illinois, 61637, United States
Tulane Medical Center
New Orleans, Louisiana, 70112, United States
Massachusetts General Hospital Cystic Fibrosis Center Clinical Research Center
Boston, Massachusetts, 02114, United States
Harper University Hospital
Detroit, Michigan, 48201, United States
New York Medical College
Valhalla, New York, 10595, United States
UNC Marisco Clinical Research Center
Chapel Hill, North Carolina, 27517, United States
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
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
The University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
Vermont Lung Center
Colchester, Vermont, 05446, United States
University of Virginia Primary Care Center
Charlottesville, Virginia, 22908, United States
West Virginia University
Morgantown, West Virginia, 26506, United States
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 Gasthuisberg
Leuven, Belgium
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
The Royal Belfast Hospital for Sick Children
Belfast, United Kingdom
Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
Birmingham, 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
Southampton General Hospital
Southampton, United Kingdom
Related Publications (1)
Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, Mall MA, Welter JJ, Ramsey BW, McKee CM, Marigowda G, Moskowitz SM, Waltz D, Sosnay PR, Simard C, Ahluwalia N, Xuan F, Zhang Y, Taylor-Cousar JL, McCoy KS; VX17-445-103 Trial Group. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1940-1948. doi: 10.1016/S0140-6736(19)32597-8. Epub 2019 Oct 31.
PMID: 31679946DERIVED
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
- Expanded Access
- Yes
Study Record Dates
First Submitted
May 2, 2018
First Posted
May 15, 2018
Study Start
August 3, 2018
Primary Completion
December 28, 2018
Study Completion
December 28, 2018
Last Updated
January 27, 2020
Results First Posted
January 27, 2020
Record last verified: 2020-01