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

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ELX/TEZ/IVA
TEZ/IVA
IVA
Sponsored by
Vertex Pharmaceuticals Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The Prince Charles Hospital
  • Institute for Respiratory Health
  • Perth Children's Hospital
  • John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital
  • The Royal Children's Hospital
  • Queensland Children's Hospital
  • Universitair Ziekenhuis Brussel - Campus Jette
  • UZ Antwerpen
  • Universitair Ziekenhuis Gent
  • Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
  • Charite Paediatric Pulmonology Department
  • Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
  • Universitatsklinikum Essen (AoR), Kinderklinik III, Abt. fur Pneumologie
  • Johann Wolfgang Goethe University
  • Mukeviszidose-Zentrum am Universitatsklinikum Jena, Klinik fuer Kinder- und Jugendmedizin
  • Universitaetsklinkum Koeln, CF-Studienzentrum
  • Pneumologisches Studienzentrum Muenchen-West
  • Klinikum Innenstadt, University of Munich
  • Belfast City Hospital
  • University Hospitals Birmingham NHS Foundation Trust
  • University Hospitals Bristol NHS Foundation Trust, Bristol Royal Hospital
  • Papworth Hospital NHS Foundation Trust, Papworth Everard
  • Western General Hospital
  • Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
  • Clinical Research Facility, Queen Elizabeth University Hospital
  • Leeds General Infirmary
  • St. James University Hospital
  • Alder Hey Children's Alder Hey Children's NHS Foundation Trust
  • Great Ormond Street Hospital for Sick Children
  • London and St Bartholomew's Hospital
  • The University Hospital of South Manchester
  • The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
  • Nottingham University Hospitals NHS Trust, Queens Medical Center
  • All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
  • Southampton General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

TEZ/IVA

ELX/TEZ/IVA

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Absolute Change in Sweat Chloride (SwCl)
Sweat samples were collected using an approved collection device.
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Full Information

First Posted
September 24, 2019
Last Updated
July 23, 2021
Sponsor
Vertex Pharmaceuticals Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT04105972
Brief Title
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

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
October 3, 2019 (Actual)
Primary Completion Date
July 24, 2020 (Actual)
Study Completion Date
July 24, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
176 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TEZ/IVA
Arm Type
Active Comparator
Arm Description
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.
Arm Title
ELX/TEZ/IVA
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ELX/TEZ/IVA
Other Intervention Name(s)
VX-445/VX-661/VX-770, elexacaftor/tezacaftor/ivacaftor
Intervention Description
FDC tablet for oral administration.
Intervention Type
Drug
Intervention Name(s)
TEZ/IVA
Other Intervention Name(s)
VX-661/VX-770, tezacaftor/ivacaftor
Intervention Description
Fixed-dose combination (FDC) tablet for oral administration.
Intervention Type
Drug
Intervention Name(s)
IVA
Other Intervention Name(s)
VX-770, ivacaftor
Intervention Description
Mono tablet for oral administration.
Primary Outcome Measure Information:
Title
Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Description
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.
Time Frame
From Baseline Through Week 24
Secondary Outcome Measure Information:
Title
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame
From Baseline Through Week 24
Title
Absolute Change in Sweat Chloride (SwCl)
Description
Sweat samples were collected using an approved collection device.
Time Frame
From Baseline Through Week 24
Title
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
The Prince Charles Hospital
City
Chermside
Country
Australia
Facility Name
Institute for Respiratory Health
City
Nedlands
Country
Australia
Facility Name
Perth Children's Hospital
City
Nedlands
Country
Australia
Facility Name
John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital
City
New Lambton
Country
Australia
Facility Name
The Royal Children's Hospital
City
Parkville, VIC
Country
Australia
Facility Name
Queensland Children's Hospital
City
South Brisbane
Country
Australia
Facility Name
Universitair Ziekenhuis Brussel - Campus Jette
City
Brussels
Country
Belgium
Facility Name
UZ Antwerpen
City
Edegem
Country
Belgium
Facility Name
Universitair Ziekenhuis Gent
City
Gent
Country
Belgium
Facility Name
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
City
Leuven
Country
Belgium
Facility Name
Charite Paediatric Pulmonology Department
City
Berlin
Country
Germany
Facility Name
Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
City
Essen
Country
Germany
Facility Name
Universitatsklinikum Essen (AoR), Kinderklinik III, Abt. fur Pneumologie
City
Essen
Country
Germany
Facility Name
Johann Wolfgang Goethe University
City
Frankfurt
Country
Germany
Facility Name
Mukeviszidose-Zentrum am Universitatsklinikum Jena, Klinik fuer Kinder- und Jugendmedizin
City
Jena
Country
Germany
Facility Name
Universitaetsklinkum Koeln, CF-Studienzentrum
City
Koeln
Country
Germany
Facility Name
Pneumologisches Studienzentrum Muenchen-West
City
Muenchen
Country
Germany
Facility Name
Klinikum Innenstadt, University of Munich
City
München
Country
Germany
Facility Name
Belfast City Hospital
City
Belfast
Country
United Kingdom
Facility Name
University Hospitals Birmingham NHS Foundation Trust
City
Birmingham
Country
United Kingdom
Facility Name
University Hospitals Bristol NHS Foundation Trust, Bristol Royal Hospital
City
Bristol
Country
United Kingdom
Facility Name
Papworth Hospital NHS Foundation Trust, Papworth Everard
City
Cambridge
Country
United Kingdom
Facility Name
Western General Hospital
City
Edinburgh
Country
United Kingdom
Facility Name
Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
City
Exeter
Country
United Kingdom
Facility Name
Clinical Research Facility, Queen Elizabeth University Hospital
City
Glasgow
Country
United Kingdom
Facility Name
Leeds General Infirmary
City
Leeds, West Yorkshire
Country
United Kingdom
Facility Name
St. James University Hospital
City
Leeds
Country
United Kingdom
Facility Name
Alder Hey Children's Alder Hey Children's NHS Foundation Trust
City
Liverpool
Country
United Kingdom
Facility Name
Great Ormond Street Hospital for Sick Children
City
London
Country
United Kingdom
Facility Name
London and St Bartholomew's Hospital
City
London
Country
United Kingdom
Facility Name
The University Hospital of South Manchester
City
Manchester
Country
United Kingdom
Facility Name
The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
City
Newcastle Upon Tyne
Country
United Kingdom
Facility Name
Nottingham University Hospitals NHS Trust, Queens Medical Center
City
Nottingham
Country
United Kingdom
Facility Name
All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
City
Penarth
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
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.
Citations:
PubMed Identifier
34942085
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.
Results Reference
derived
PubMed Identifier
33331662
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.
Results Reference
derived

Learn more about this trial

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

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