Evaluation of Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) in Cystic Fibrosis Subjects Without an F508del Mutation

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05274269
• Other study ID #: VX21-445-124
• Secondary ID: 2021-005320-38
• Status: Completed
• Phase: Phase 3
• Start date: May 9, 2022
• Est. completion date: July 5, 2023

Study information

• Verified date: July 2023
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 307
• Est. completion date: July 5, 2023
• Est. primary completion date: July 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• ELX/TEZ/IVA
Fixed-dose combination (FDC) tablets for oral administration.
• IVA
Tablet for oral administration.

Other:
• Placebo (matched to ELX/TEZ/IVA)
Placebo matched to ELX/TEZ/IVA for oral administration.
• Placebo (matched to IVA)
Placebo matched to IVA for oral administration.

Locations

Country	Name	City	State
Austria	Medizinische Universität Innsbruck	Innsbruck
Belgium	Cliniques Universitaires de Bruxelles Hopital Erasme	Brussels
Belgium	Universitair Ziekenhuis Brussel - Campus Jette	Brussels
Belgium	Universitair Ziekenhuis Antwerpen (UZA) - Antwerp University Hospital	Edegem
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven
Belgium	Cliniques Universitaires Saint-Luc	Woluwe-Saint-Lambert
Canada	University of Alberta Hospital, Edmonton Clinic	Edmonton
Canada	Centre Hospitalier de l'Universite de Montreal (CHUM) Hotel-Dieu	Montreal
Canada	McGill University Health Centre, Glen Site, Montreal Children's Hospital	Montreal
Canada	The Hospital for Sick Children	Toronto
Canada	British Columbia Children's Hospital	Vancouver
Canada	St. Paul's Hospital	Vancouver
Czechia	Klinika Detskych Infekcnich Nemoci	Brno
Czechia	Fakultni nemocnice v Motole	Praha 5
France	CHU Lyon - Hopital Femme Mere-Enfant	Bron Cedex
France	Centre Hospitalier Intercommunal Creteil	Créteil
France	Institut Cœur Poumon, CHU de Lille	Lille
France	CHU Marseille - Hopital Nord	Marseille
France	Hopital Arnaud de Villeneuve	Montpellier Cedex 5
France	Centre Hospitalier Universitaire De Nantes - G. R. Laennec	Nantes
France	Centre Hospitalier Universitaire (CHU) de Nice - Hopital Pasteur	Nice
France	Hopital Cochin	Paris
France	Hopital Robert Debre	Paris
France	Hopital Necker, Enfants Malades	Paris Cedex 15
France	Hopital Haut-Leveque - CRCM Adulte	Pessac
France	Centre Hospitalier Lyon Sud	Pierre-Bénite
France	Centre Hospitalier Universitaire De Reims, Hopital Sebastopol	Reims
France	CHU de Rennes - Hôpital Sud	Rennes
France	Centre de Perharidy	Roscoff Cedex
France	CHU de Toulouse - Hopital Larre	Toulouse
France	Hopital Bretonneau	Tours
Germany	Charite Paediatric Pulmonology Department	Berlin
Germany	Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital	Erlangen
Germany	Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen	Essen
Germany	Johann Wolfgang Goethe University	Frankfurt
Germany	Justus-Liebig-Universität Gießen Zentrum für Kinderheilkunde und Jugendmedizin	Gießen
Germany	Universitätsklinikum Halle (Saale) / Universitätsklinik und Poliklinik für Innere Medizin, Schwerpunkt Pneumologie	Halle
Germany	Hannover Medical School	Hannover
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitaetsklinikum Jena, Mukoviszidose-Zentrum	Jena
Germany	Universitaetsklinkum Koeln, CF-Studienzentrum	Koeln
Germany	Johannes Gutenberg-Universitaet	Mainz
Germany	Pneumologisches Studienzentrum Muenchen-West	Muenchen
Germany	Dr. von Haunersches Kinderspital	München
Germany	Klinikum Innenstadt, University of Munich	München
Germany	Klinik fur Kinder- und Jugendmedizin, Universitatsklinikum Munster	Münster
Germany	Klinikum Westbrandenburg (CF)	Potsdam
Germany	Universitätsklinikum Tübingen Klinik für Kinder- und Jugendmedizin	Tuebingen
Germany	Universitätsklinikum Ulm, Klinik für Kinder- und Jugendmedizin (CF)	Ulm
Germany	Universitätsklinikum Würzburg	Würzburg
Hungary	National Koranyi Institute for TBC and Pulmonology	Budapest
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona	Ancona
Italy	Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer	Firenze
Italy	IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico	Genova
Italy	Azienda Ospedaliera Universitaria Policlinico G. Martino	Messina
Italy	Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena	Milan
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliera Universitaria Federico II (Adults)	Naples
Italy	Malattie Apparato Respiratorio 2 - Centro Fibrosi Cistica	Orbassano
Italy	Centro Regionale Fibrosi Cistica, A.O. Ospedale San Carlo	Potenza
Italy	Ospedale Pediatrico Bambino Gesu	Rome
Italy	Azienda Ospedaliera di Verona - Ospedale Civile Maggiore	Verona
Netherlands	Academisch Medisch Centrum (Academic Medical Centre)	Amsterdam
Netherlands	HagaZiekenhuis van den Haag	Den Haag
Netherlands	UMC St. Radboud	Nijmegen
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Norway	Oslo University Hospital, Department of Paediatric Medicine	Oslo
Poland	Pediatric Hospital Polanki named of Maciej Plazynski	Gdansk
Poland	Instytut Matki i Dziecka, Klinika Mukowiscydozy IMiD, Oddzial Chorób Pluc SZPZOZ im.Dzieci Warszawy w Dziekanowie Lesnym	Lomianki
Poland	Institute of Tuberculosis and Lung Diseases	Rabka-Zdrój
Portugal	Hospital de Santa Maria	Lisbon
Portugal	Hospital Sao Joao	Porto
Spain	Hospital de Cruces	Barakaldo
Spain	Hospital Saint Joan de Deu	Barcelona
Spain	Hospital Universitari Vall d Hebron	Barcelona
Spain	Hospital Universitari Vall d´Hebron Servicio de Broncoscopia	Barcelona
Spain	Hospital Universitario de Jerez de la Frontera	Jerez De La Frontera
Spain	Hospital Infantil Universitario Nino Jesus	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Infantil La Paz	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Virgen de la Arrixaca	Murcia
Spain	Corporacio Sanitaria Parc Tauli - Sabadell Hospital Universitari	Sabadell
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitario y Politecnico La Fe	Valencia
Sweden	Sahlgrenska Universitetssjukhuset	Göteborg
Sweden	Karolinska Universitetssjukhuset, Huddinge	Stockholm
Switzerland	Kinderspital Zuerich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

Austria,  Belgium,  Canada,  Czechia,  France,  Germany,  Hungary,  Italy,  Netherlands,  Norway,  Poland,  Portugal,  Spain,  Sweden,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)		From Baseline Through Week 24
Secondary	Absolute Change in Sweat Chloride (SwCl)		From Baseline Through Week 24
Secondary	Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain (RD) Score		From Baseline Through Week 24
Secondary	Absolute Change in Body Mass Index (BMI)		From Baseline at Week 24
Secondary	Absolute Change in Weight		From Baseline at Week 24
Secondary	Number of Pulmonary Exacerbations (PEx)		From Baseline Through Week 24
Secondary	Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)		Day 1 up to Week 28