Evaluation of Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) in Cystic Fibrosis Subjects Without an F508del Mutation
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ELX/TEZ/IVA
IVA
Placebo (matched to ELX/TEZ/IVA)
Placebo (matched to IVA)
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis
Eligibility Criteria
Key Inclusion Criteria:
- Participant has a qualifying ELX/TEZ/IVA-responsive CFTR mutation and does not have an exclusionary CFTR mutation
- Forced expiratory volume in 1 second (FEV1) value >=40% and <=90% of predicted mean for age, sex, and height
Key Exclusion Criteria:
- History of solid organ or hematological transplantation
- Clinically significant cirrhosis with or without portal hypertension
- Lung infection with organisms associated with a more rapid decline in pulmonary status
Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- Medizinische Universität Innsbruck
- Cliniques Universitaires de Bruxelles Hopital Erasme
- Universitair Ziekenhuis Brussel - Campus Jette
- Universitair Ziekenhuis Antwerpen (UZA) - Antwerp University Hospital
- Universitair Ziekenhuis Gent
- Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
- Cliniques Universitaires Saint-Luc
- University of Alberta Hospital, Edmonton Clinic
- Centre Hospitalier de l'Universite de Montreal (CHUM) Hotel-Dieu
- McGill University Health Centre, Glen Site, Montreal Children's Hospital
- The Hospital for Sick Children
- British Columbia Children's Hospital
- St. Paul's Hospital
- Klinika Detskych Infekcnich Nemoci
- Fakultni nemocnice v Motole
- CHU Lyon - Hopital Femme Mere-Enfant
- Centre Hospitalier Intercommunal Creteil
- Institut Cœur Poumon, CHU de Lille
- CHU Marseille - Hopital Nord
- Hopital Arnaud de Villeneuve
- Centre Hospitalier Universitaire De Nantes - G. R. Laennec
- Centre Hospitalier Universitaire (CHU) de Nice - Hopital Pasteur
- Hopital Necker, Enfants Malades
- Hopital Cochin
- Hopital Robert Debre
- Hopital Haut-Leveque - CRCM Adulte
- Centre Hospitalier Lyon Sud
- Centre Hospitalier Universitaire De Reims, Hopital Sebastopol
- CHU de Rennes - Hôpital Sud
- Centre de Perharidy
- CHU de Toulouse - Hopital Larre
- Hopital Bretonneau
- Charite Paediatric Pulmonology Department
- Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital
- Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
- Johann Wolfgang Goethe University
- Justus-Liebig-Universität Gießen Zentrum für Kinderheilkunde und Jugendmedizin
- Universitätsklinikum Halle (Saale) / Universitätsklinik und Poliklinik für Innere Medizin, Schwerpunkt Pneumologie
- Hannover Medical School
- Medizinische Hochschule Hannover
- Universitaetsklinikum Jena, Mukoviszidose-Zentrum
- Universitaetsklinkum Koeln, CF-Studienzentrum
- Johannes Gutenberg-Universitaet
- Pneumologisches Studienzentrum Muenchen-West
- Dr. von Haunersches Kinderspital
- Klinikum Innenstadt, University of Munich
- Klinik fur Kinder- und Jugendmedizin, Universitatsklinikum Munster
- Klinikum Westbrandenburg (CF)
- Universitätsklinikum Tübingen Klinik für Kinder- und Jugendmedizin
- Universitätsklinikum Ulm, Klinik für Kinder- und Jugendmedizin (CF)
- Universitätsklinikum Würzburg
- National Koranyi Institute for TBC and Pulmonology
- Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
- Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer
- IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico
- Azienda Ospedaliera Universitaria Policlinico G. Martino
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
- Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
- Azienda Ospedaliera Universitaria Federico II (Adults)
- Malattie Apparato Respiratorio 2 - Centro Fibrosi Cistica
- Centro Regionale Fibrosi Cistica, A.O. Ospedale San Carlo
- Ospedale Pediatrico Bambino Gesu
- Azienda Ospedaliera di Verona - Ospedale Civile Maggiore
- Academisch Medisch Centrum (Academic Medical Centre)
- HagaZiekenhuis van den Haag
- UMC St. Radboud
- Erasmus Medical Center
- Universitair Medisch Centrum Utrecht
- Oslo University Hospital, Department of Paediatric Medicine
- Pediatric Hospital Polanki named of Maciej Płażyński
- Institute of Tuberculosis and Lung Diseases
- Instytut Matki i Dziecka, Klinika Mukowiscydozy IMiD, Oddział Chorób Płuc SZPZOZ im.Dzieci Warszawy w Dziekanowie Leśnym
- Hospital de Santa Maria
- Hospital Sao Joao
- Hospital de Cruces
- Hospital Saint Joan de Deu
- Hospital Universitari Vall d Hebron
- Hospital Universitari Vall d´Hebron Servicio de Broncoscopia
- Hospital Universitario de Jerez de la Frontera
- Hospital Infantil Universitario Nino Jesus
- Hospital Universitario 12 de Octubre
- Hospital Universitario Infantil La Paz
- Hospital Universitario Ramon y Cajal
- Hospital Virgen de la Arrixaca
- Corporacio Sanitaria Parc Tauli - Sabadell Hospital Universitari
- Hospital Universitario Virgen del Rocio
- Hospital Universitario y Politecnico La Fe
- Sahlgrenska Universitetssjukhuset
- Karolinska Universitetssjukhuset, Huddinge
- Kinderspital Zuerich
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
ELX/TEZ/IVA
Placebo
Arm Description
Participants will receive ELX/TEZ/IVA in the morning and IVA in the evening.
Participants will receive placebo matched to ELX/TEZ/IVA in the morning and placebo matched to IVA in the evening.
Outcomes
Primary Outcome Measures
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Secondary Outcome Measures
Absolute Change in Sweat Chloride (SwCl)
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain (RD) Score
Absolute Change in Body Mass Index (BMI)
Absolute Change in Weight
Number of Pulmonary Exacerbations (PEx)
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Full Information
NCT ID
NCT05274269
First Posted
March 1, 2022
Last Updated
July 28, 2023
Sponsor
Vertex Pharmaceuticals Incorporated
1. Study Identification
Unique Protocol Identification Number
NCT05274269
Brief Title
Evaluation of Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) in Cystic Fibrosis Subjects Without an F508del Mutation
Official Title
A Phase 3 Double-blind, Randomized, Placebo-controlled Study Evaluating the Efficacy and Safety of ELX/TEZ/IVA in Cystic Fibrosis Subjects 6 Years of Age and Older With a Non-F508del ELX/TEZ/IVA-responsive CFTR Mutation
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
May 9, 2022 (Actual)
Primary Completion Date
July 5, 2023 (Actual)
Study Completion Date
July 5, 2023 (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
Product Manufactured in and Exported from the U.S.
Yes
5. Study Description
Brief Summary
This study will evaluate the efficacy, pharmacodynamics (PD) and safety of ELX/TEZ/IVA in participants 6 years of age and older with a non-F508del ELX/TEZ/IVA-responsive cystic fibrosis transmembrane conductance regulator gene (CFTR) mutation.
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
307 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ELX/TEZ/IVA
Arm Type
Experimental
Arm Description
Participants will receive ELX/TEZ/IVA in the morning and IVA in the evening.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo matched to ELX/TEZ/IVA in the morning and placebo matched to IVA in the evening.
Intervention Type
Drug
Intervention Name(s)
ELX/TEZ/IVA
Other Intervention Name(s)
VX-445/VX-661/VX-770, elexacaftor/tezacaftor/ivacaftor
Intervention Description
Fixed-dose combination (FDC) tablets for oral administration.
Intervention Type
Drug
Intervention Name(s)
IVA
Other Intervention Name(s)
VX-770, ivacaftor
Intervention Description
Tablet for oral administration.
Intervention Type
Other
Intervention Name(s)
Placebo (matched to ELX/TEZ/IVA)
Intervention Description
Placebo matched to ELX/TEZ/IVA for oral administration.
Intervention Type
Other
Intervention Name(s)
Placebo (matched to IVA)
Intervention Description
Placebo matched to IVA for oral administration.
Primary Outcome Measure Information:
Title
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Time Frame
From Baseline Through Week 24
Secondary Outcome Measure Information:
Title
Absolute Change in Sweat Chloride (SwCl)
Time Frame
From Baseline Through Week 24
Title
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain (RD) Score
Time Frame
From Baseline Through Week 24
Title
Absolute Change in Body Mass Index (BMI)
Time Frame
From Baseline at Week 24
Title
Absolute Change in Weight
Time Frame
From Baseline at Week 24
Title
Number of Pulmonary Exacerbations (PEx)
Time Frame
From Baseline Through Week 24
Title
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
Day 1 up to Week 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Participant has a qualifying ELX/TEZ/IVA-responsive CFTR mutation and does not have an exclusionary CFTR mutation
Forced expiratory volume in 1 second (FEV1) value >=40% and <=100% of predicted mean for age, sex, and height
Key Exclusion Criteria:
History of solid organ or hematological transplantation
Clinically significant cirrhosis with or without portal hypertension
Lung infection with organisms associated with a more rapid decline in pulmonary status
Other protocol defined Inclusion/Exclusion criteria may apply.
Facility Information:
Facility Name
Medizinische Universität Innsbruck
City
Innsbruck
Country
Austria
Facility Name
Cliniques Universitaires de Bruxelles Hopital Erasme
City
Brussels
Country
Belgium
Facility Name
Universitair Ziekenhuis Brussel - Campus Jette
City
Brussels
Country
Belgium
Facility Name
Universitair Ziekenhuis Antwerpen (UZA) - Antwerp University Hospital
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
Cliniques Universitaires Saint-Luc
City
Woluwe-Saint-Lambert
Country
Belgium
Facility Name
University of Alberta Hospital, Edmonton Clinic
City
Edmonton
Country
Canada
Facility Name
Centre Hospitalier de l'Universite de Montreal (CHUM) Hotel-Dieu
City
Montreal
Country
Canada
Facility Name
McGill University Health Centre, Glen Site, Montreal Children's Hospital
City
Montreal
Country
Canada
Facility Name
The Hospital for Sick Children
City
Toronto
Country
Canada
Facility Name
British Columbia Children's Hospital
City
Vancouver
Country
Canada
Facility Name
St. Paul's Hospital
City
Vancouver
Country
Canada
Facility Name
Klinika Detskych Infekcnich Nemoci
City
Brno
Country
Czechia
Facility Name
Fakultni nemocnice v Motole
City
Praha 5
Country
Czechia
Facility Name
CHU Lyon - Hopital Femme Mere-Enfant
City
Bron Cedex
Country
France
Facility Name
Centre Hospitalier Intercommunal Creteil
City
Créteil
Country
France
Facility Name
Institut Cœur Poumon, CHU de Lille
City
Lille
Country
France
Facility Name
CHU Marseille - Hopital Nord
City
Marseille
Country
France
Facility Name
Hopital Arnaud de Villeneuve
City
Montpellier Cedex 5
Country
France
Facility Name
Centre Hospitalier Universitaire De Nantes - G. R. Laennec
City
Nantes
Country
France
Facility Name
Centre Hospitalier Universitaire (CHU) de Nice - Hopital Pasteur
City
Nice
Country
France
Facility Name
Hopital Necker, Enfants Malades
City
Paris Cedex 15
Country
France
Facility Name
Hopital Cochin
City
Paris
Country
France
Facility Name
Hopital Robert Debre
City
Paris
Country
France
Facility Name
Hopital Haut-Leveque - CRCM Adulte
City
Pessac
Country
France
Facility Name
Centre Hospitalier Lyon Sud
City
Pierre-Bénite
Country
France
Facility Name
Centre Hospitalier Universitaire De Reims, Hopital Sebastopol
City
Reims
Country
France
Facility Name
CHU de Rennes - Hôpital Sud
City
Rennes
Country
France
Facility Name
Centre de Perharidy
City
Roscoff Cedex
Country
France
Facility Name
CHU de Toulouse - Hopital Larre
City
Toulouse
Country
France
Facility Name
Hopital Bretonneau
City
Tours
Country
France
Facility Name
Charite Paediatric Pulmonology Department
City
Berlin
Country
Germany
Facility Name
Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital
City
Erlangen
Country
Germany
Facility Name
Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
City
Essen
Country
Germany
Facility Name
Johann Wolfgang Goethe University
City
Frankfurt
Country
Germany
Facility Name
Justus-Liebig-Universität Gießen Zentrum für Kinderheilkunde und Jugendmedizin
City
Gießen
Country
Germany
Facility Name
Universitätsklinikum Halle (Saale) / Universitätsklinik und Poliklinik für Innere Medizin, Schwerpunkt Pneumologie
City
Halle
Country
Germany
Facility Name
Hannover Medical School
City
Hannover
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
Country
Germany
Facility Name
Universitaetsklinikum Jena, Mukoviszidose-Zentrum
City
Jena
Country
Germany
Facility Name
Universitaetsklinkum Koeln, CF-Studienzentrum
City
Koeln
Country
Germany
Facility Name
Johannes Gutenberg-Universitaet
City
Mainz
Country
Germany
Facility Name
Pneumologisches Studienzentrum Muenchen-West
City
Muenchen
Country
Germany
Facility Name
Dr. von Haunersches Kinderspital
City
München
Country
Germany
Facility Name
Klinikum Innenstadt, University of Munich
City
München
Country
Germany
Facility Name
Klinik fur Kinder- und Jugendmedizin, Universitatsklinikum Munster
City
Münster
Country
Germany
Facility Name
Klinikum Westbrandenburg (CF)
City
Potsdam
Country
Germany
Facility Name
Universitätsklinikum Tübingen Klinik für Kinder- und Jugendmedizin
City
Tuebingen
Country
Germany
Facility Name
Universitätsklinikum Ulm, Klinik für Kinder- und Jugendmedizin (CF)
City
Ulm
Country
Germany
Facility Name
Universitätsklinikum Würzburg
City
Würzburg
Country
Germany
Facility Name
National Koranyi Institute for TBC and Pulmonology
City
Budapest
Country
Hungary
Facility Name
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
City
Ancona
Country
Italy
Facility Name
Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer
City
Firenze
Country
Italy
Facility Name
IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico
City
Genova
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Policlinico G. Martino
City
Messina
Country
Italy
Facility Name
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
City
Milano
Country
Italy
Facility Name
Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
City
Milan
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Federico II (Adults)
City
Naples
Country
Italy
Facility Name
Malattie Apparato Respiratorio 2 - Centro Fibrosi Cistica
City
Orbassano
Country
Italy
Facility Name
Centro Regionale Fibrosi Cistica, A.O. Ospedale San Carlo
City
Potenza
Country
Italy
Facility Name
Ospedale Pediatrico Bambino Gesu
City
Rome
Country
Italy
Facility Name
Azienda Ospedaliera di Verona - Ospedale Civile Maggiore
City
Verona
Country
Italy
Facility Name
Academisch Medisch Centrum (Academic Medical Centre)
City
Amsterdam
Country
Netherlands
Facility Name
HagaZiekenhuis van den Haag
City
Den Haag
Country
Netherlands
Facility Name
UMC St. Radboud
City
Nijmegen
Country
Netherlands
Facility Name
Erasmus Medical Center
City
Rotterdam
Country
Netherlands
Facility Name
Universitair Medisch Centrum Utrecht
City
Utrecht
Country
Netherlands
Facility Name
Oslo University Hospital, Department of Paediatric Medicine
City
Oslo
Country
Norway
Facility Name
Pediatric Hospital Polanki named of Maciej Płażyński
City
Gdańsk
Country
Poland
Facility Name
Institute of Tuberculosis and Lung Diseases
City
Rabka-Zdrój
Country
Poland
Facility Name
Instytut Matki i Dziecka, Klinika Mukowiscydozy IMiD, Oddział Chorób Płuc SZPZOZ im.Dzieci Warszawy w Dziekanowie Leśnym
City
Łomianki
Country
Poland
Facility Name
Hospital de Santa Maria
City
Lisbon
Country
Portugal
Facility Name
Hospital Sao Joao
City
Porto
Country
Portugal
Facility Name
Hospital de Cruces
City
Barakaldo
Country
Spain
Facility Name
Hospital Saint Joan de Deu
City
Barcelona
Country
Spain
Facility Name
Hospital Universitari Vall d Hebron
City
Barcelona
Country
Spain
Facility Name
Hospital Universitari Vall d´Hebron Servicio de Broncoscopia
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario de Jerez de la Frontera
City
Jerez De La Frontera
Country
Spain
Facility Name
Hospital Infantil Universitario Nino Jesus
City
Madrid
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Infantil La Paz
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Ramon y Cajal
City
Madrid
Country
Spain
Facility Name
Hospital Virgen de la Arrixaca
City
Murcia
Country
Spain
Facility Name
Corporacio Sanitaria Parc Tauli - Sabadell Hospital Universitari
City
Sabadell
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio
City
Sevilla
Country
Spain
Facility Name
Hospital Universitario y Politecnico La Fe
City
Valencia
Country
Spain
Facility Name
Sahlgrenska Universitetssjukhuset
City
Göteborg
Country
Sweden
Facility Name
Karolinska Universitetssjukhuset, Huddinge
City
Stockholm
Country
Sweden
Facility Name
Kinderspital Zuerich
City
Zurich
Country
Switzerland
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
Learn more about this trial
Evaluation of Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) in Cystic Fibrosis Subjects Without an F508del Mutation
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