Clinical trial NCT04105972: A Study Evaluating the Efficacy and Safety of VX-445/Tezacaftor/Ivacaftor in Cystic Fibrosis Subjects, Homozygous for F508del
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2019-09-26
Enrollment: 176
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

* 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

Key Exclusion Criteria:

* 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

Other protocol defined Inclusion/Exclusion criteria may apply

Primary outcomes:
measure: Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score
timeFrame: From Baseline Through Week 24
Secondary outcomes:
measure: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
timeFrame: From Baseline Through Week 24
measure: Absolute Change in Sweat Chloride (SwCl)
timeFrame: From Baseline Through Week 24
measure: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: 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)
Other outcomes:
Locations:
city: Chermside
country: Australia
facility: The Prince Charles Hospital
city: Nedlands
country: Australia
facility: Institute for Respiratory Health
city: Nedlands
country: Australia
facility: Perth Children's Hospital
city: New Lambton
country: Australia
facility: John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital
city: Parkville, VIC
country: Australia
facility: The Royal Children's Hospital
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel - Campus Jette
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
city: Berlin
country: Germany
facility: Charite Paediatric Pulmonology Department
city: Essen
country: Germany
facility: Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
city: Essen
country: Germany
facility: Universitatsklinikum Essen (AoR), Kinderklinik III, Abt. fur Pneumologie
city: Frankfurt
country: Germany
facility: Johann Wolfgang Goethe University
city: Jena
country: Germany
facility: Mukeviszidose-Zentrum am Universitatsklinikum Jena, Klinik fuer Kinder- und Jugendmedizin
city: Koeln
country: Germany
facility: Universitaetsklinkum Koeln, CF-Studienzentrum
city: Muenchen
country: Germany
facility: Pneumologisches Studienzentrum Muenchen-West
city: München
country: Germany
facility: Klinikum Innenstadt, University of Munich
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust, Bristol Royal Hospital
city: Cambridge
country: United Kingdom
facility: Papworth Hospital NHS Foundation Trust, Papworth Everard
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
city: Glasgow
country: United Kingdom
facility: Clinical Research Facility, Queen Elizabeth University Hospital
city: Leeds, West Yorkshire
country: United Kingdom
facility: Leeds General Infirmary
city: Leeds
country: United Kingdom
facility: St. James University Hospital
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's Alder Hey Children's NHS Foundation Trust
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Sick Children
city: London
country: United Kingdom
facility: London and St Bartholomew's Hospital
city: Manchester
country: United Kingdom
facility: The University Hospital of South Manchester
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust, Queens Medical Center
city: Penarth
country: United Kingdom
facility: All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
References:
citation: Sutharsan 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.
citation: 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. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.