A Study Evaluating the Efficacy and Safety of VX-445/Tezacaftor/Ivacaftor in Cystic Fibrosis Subjects, Homozygous for F508del

NCT ID: NCT04105972

Last Updated: 2021-08-18

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

176 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-03

Study Completion Date

2020-07-24

Brief Summary

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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.

Detailed Description

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Conditions

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Cystic Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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TEZ/IVA

Following 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.

Group Type ACTIVE_COMPARATOR

TEZ/IVA

Intervention Type DRUG

Fixed-dose combination (FDC) tablet for oral administration.

IVA

Intervention Type DRUG

Mono tablet for oral administration.

ELX/TEZ/IVA

Following 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.

Group Type EXPERIMENTAL

ELX/TEZ/IVA

Intervention Type DRUG

FDC tablet for oral administration.

IVA

Intervention Type DRUG

Mono tablet for oral administration.

Interventions

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ELX/TEZ/IVA

FDC tablet for oral administration.

Intervention Type DRUG

TEZ/IVA

Fixed-dose combination (FDC) tablet for oral administration.

Intervention Type DRUG

IVA

Mono tablet for oral administration.

Intervention Type DRUG

Other Intervention Names

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VX-445/VX-661/VX-770 elexacaftor/tezacaftor/ivacaftor VX-661/VX-770 tezacaftor/ivacaftor VX-770 ivacaftor

Eligibility Criteria

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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

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
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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The Prince Charles Hospital

Chermside, , Australia

Site Status

Institute for Respiratory Health

Nedlands, , Australia

Site Status

Perth Children's Hospital

Nedlands, , Australia

Site Status

John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital

New Lambton, , Australia

Site Status

The Royal Children's Hospital

Parkville, VIC, , Australia

Site Status

Queensland Children's Hospital

South Brisbane, , Australia

Site Status

Universitair Ziekenhuis Brussel - Campus Jette

Brussels, , Belgium

Site Status

UZ Antwerpen

Edegem, , Belgium

Site Status

Universitair Ziekenhuis Gent

Ghent, , Belgium

Site Status

Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg

Leuven, , Belgium

Site Status

Charite Paediatric Pulmonology Department

Berlin, , Germany

Site Status

Universitaetsklinkum Koeln, CF-Studienzentrum

Cologne, , Germany

Site Status

Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen

Essen, , Germany

Site Status

Universitatsklinikum Essen (AoR), Kinderklinik III, Abt. fur Pneumologie

Essen, , Germany

Site Status

Johann Wolfgang Goethe University

Frankfurt, , Germany

Site Status

Mukeviszidose-Zentrum am Universitatsklinikum Jena, Klinik fuer Kinder- und Jugendmedizin

Jena, , Germany

Site Status

Klinikum Innenstadt, University of Munich

München, , Germany

Site Status

Pneumologisches Studienzentrum Muenchen-West

München, , Germany

Site Status

Belfast City Hospital

Belfast, , United Kingdom

Site Status

University Hospitals Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Site Status

University Hospitals Bristol NHS Foundation Trust, Bristol Royal Hospital

Bristol, , United Kingdom

Site Status

Papworth Hospital NHS Foundation Trust, Papworth Everard

Cambridge, , United Kingdom

Site Status

Western General Hospital

Edinburgh, , United Kingdom

Site Status

Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital

Exeter, , United Kingdom

Site Status

Clinical Research Facility, Queen Elizabeth University Hospital

Glasgow, , United Kingdom

Site Status

St. James University Hospital

Leeds, , United Kingdom

Site Status

Leeds General Infirmary

Leeds, West Yorkshire, , United Kingdom

Site Status

Alder Hey Children's Alder Hey Children's NHS Foundation Trust

Liverpool, , United Kingdom

Site Status

Great Ormond Street Hospital for Sick Children

London, , United Kingdom

Site Status

London and St Bartholomew's Hospital

London, , United Kingdom

Site Status

The University Hospital of South Manchester

Manchester, , United Kingdom

Site Status

The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary

Newcastle upon Tyne, , United Kingdom

Site Status

Nottingham University Hospitals NHS Trust, Queens Medical Center

Nottingham, , United Kingdom

Site Status

All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough

Penarth, , United Kingdom

Site Status

Southampton General Hospital

Southampton, , United Kingdom

Site Status

Countries

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Australia Belgium Germany United Kingdom

References

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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.

Reference Type DERIVED
PMID: 37983082 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34942085 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33331662 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2019-001735-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VX18-445-109

Identifier Type: -

Identifier Source: org_study_id

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