A Study Evaluating the Efficacy and Safety of VX-445/Tezacaftor/Ivacaftor in Cystic Fibrosis Subjects, Homozygous for F508del
A Phase 3b, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-445/Tezacaftor/Ivacaftor in Cystic Fibrosis Subjects, Homozygous for F508del
2 other identifiers
interventional
176
4 countries
35
Brief Summary
This study will evaluate the efficacy, safety, and pharmacodynamics of elexacaftor (ELX, VX-445) in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous for F508del.
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 Oct 2019
Shorter than P25 for phase_3
35 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
September 24, 2019
CompletedFirst Posted
Study publicly available on registry
September 26, 2019
CompletedStudy Start
First participant enrolled
October 3, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 24, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
July 24, 2020
CompletedResults Posted
Study results publicly available
August 18, 2021
CompletedAugust 18, 2021
July 1, 2021
10 months
September 24, 2019
July 23, 2021
July 23, 2021
Conditions
Outcome Measures
Primary Outcomes (1)
Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
From Baseline Through Week 24
Secondary Outcomes (3)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
From Baseline Through Week 24
Absolute Change in Sweat Chloride (SwCl)
From Baseline Through Week 24
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
From Day 1 in the 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 28)
Study Arms (2)
TEZ/IVA
ACTIVE COMPARATORFollowing TEZ/IVA run-in period of 4 weeks, participants received TEZ 100 milligrams (mg) once daily (qd)/IVA 150 mg every 12 hours (q12h) in the treatment period for 24 weeks.
ELX/TEZ/IVA
EXPERIMENTALFollowing TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.
Interventions
FDC tablet for oral administration.
Fixed-dose combination (FDC) tablet for oral administration.
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 (35)
The Prince Charles Hospital
Chermside, Australia
Institute for Respiratory Health
Nedlands, Australia
Perth Children's Hospital
Nedlands, Australia
John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital
New Lambton, Australia
The Royal Children's Hospital
Parkville, VIC, Australia
Queensland Children's Hospital
South Brisbane, Australia
Universitair Ziekenhuis Brussel - Campus Jette
Brussels, Belgium
UZ Antwerpen
Edegem, Belgium
Universitair Ziekenhuis Gent
Ghent, Belgium
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
Leuven, Belgium
Charite Paediatric Pulmonology Department
Berlin, Germany
Universitaetsklinkum Koeln, CF-Studienzentrum
Cologne, Germany
Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
Essen, Germany
Universitatsklinikum Essen (AoR), Kinderklinik III, Abt. fur Pneumologie
Essen, Germany
Johann Wolfgang Goethe University
Frankfurt, Germany
Mukeviszidose-Zentrum am Universitatsklinikum Jena, Klinik fuer Kinder- und Jugendmedizin
Jena, Germany
Klinikum Innenstadt, University of Munich
München, Germany
Pneumologisches Studienzentrum Muenchen-West
München, Germany
Belfast City Hospital
Belfast, United Kingdom
University Hospitals Birmingham NHS Foundation Trust
Birmingham, United Kingdom
University Hospitals Bristol NHS Foundation Trust, Bristol Royal Hospital
Bristol, United Kingdom
Papworth Hospital NHS Foundation Trust, Papworth Everard
Cambridge, United Kingdom
Western General Hospital
Edinburgh, United Kingdom
Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
Exeter, United Kingdom
Clinical Research Facility, Queen Elizabeth University Hospital
Glasgow, United Kingdom
St. James University Hospital
Leeds, United Kingdom
Leeds General Infirmary
Leeds, West Yorkshire, United Kingdom
Alder Hey Children's Alder Hey Children's NHS Foundation Trust
Liverpool, United Kingdom
Great Ormond Street Hospital for Sick Children
London, United Kingdom
London and St Bartholomew's Hospital
London, United Kingdom
The University Hospital of South Manchester
Manchester, United Kingdom
The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
Newcastle upon Tyne, United Kingdom
Nottingham University Hospitals NHS Trust, Queens Medical Center
Nottingham, United Kingdom
All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
Penarth, United Kingdom
Southampton General Hospital
Southampton, United Kingdom
Related Publications (3)
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: 37983082DERIVEDSutharsan S, McKone EF, Downey DG, Duckers J, MacGregor G, Tullis E, Van Braeckel E, Wainwright CE, Watson D, Ahluwalia N, Bruinsma BG, Harris C, Lam AP, Lou Y, Moskowitz SM, Tian S, Yuan J, Waltz D, Mall MA; VX18-445-109 study group. Efficacy and safety of elexacaftor plus tezacaftor plus ivacaftor versus tezacaftor plus ivacaftor in people with cystic fibrosis homozygous for F508del-CFTR: a 24-week, multicentre, randomised, double-blind, active-controlled, phase 3b trial. Lancet Respir Med. 2022 Mar;10(3):267-277. doi: 10.1016/S2213-2600(21)00454-9. Epub 2021 Dec 20.
PMID: 34942085DERIVEDSouthern 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. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
PMID: 33331662DERIVED
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
- Restriction Type
- OTHER
- 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
September 24, 2019
First Posted
September 26, 2019
Study Start
October 3, 2019
Primary Completion
July 24, 2020
Study Completion
July 24, 2020
Last Updated
August 18, 2021
Results First Posted
August 18, 2021
Record last verified: 2021-07
Data Sharing
- IPD Sharing
- Will not share
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.