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

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

This study evaluated 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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: ELX/TEZ/IVA; Drug: IVA; Other: Placebo (matched to ELX/TEZ/IVA); Other: Placebo (matched to IVA)

• Study Type: Interventional
• Enrollment (Actual): 307
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received placebo matched to ELX/TEZ/IVA FDC in the morning and placebo matched to IVA in the evening for 24 weeks.	Other: Placebo (matched to ELX/TEZ/IVA); Placebo matched to ELX/TEZ/IVA for oral administration.; Other: Placebo (matched to IVA); Placebo matched to IVA for oral administration.
Experimental: ELX/TEZ/IVA; Participants 6 to less than (<) 12 years of age and weighing <30 kilogram (kg) at Day 1 received ELX 100 milligram (mg)/TEZ 50 mg /IVA 75 mg as fixed dose combination (FDC) tablets in the morning and IVA as mono tablet in the evening and those weighing more than or equal to (≥) 30 kg at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 24 weeks. Participants ≥12 years age at Day 1 received ELX 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA as mono tablet in the evening for 24 weeks.	Drug: ELX/TEZ/IVA; Fixed-dose combination (FDC) tablets for oral administration.; Other Names: VX-445/VX-661/VX-770; elexacaftor/tezacaftor/ivacaftor; Drug: IVA; Tablet for oral administration.; Other Names: VX-770; ivacaftor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From Baseline Through Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in Weight		From Baseline at Week 24
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)		Day 1 up to Week 28
Absolute Change in Sweat Chloride (SwCl)	Sweat samples were collected using an approved collection device.	From Baseline Through Week 24
Absolute Change in Body Mass Index (BMI)	BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).	From Baseline at Week 24
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain (RD) 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.	From Baseline Through Week 24
Number of Pulmonary Exacerbations (PEx)	Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.	From Baseline Through Week 24

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2022
• Primary Completion (Actual): July 5, 2023
• Study Completion (Actual): July 5, 2023

Study Registration Dates

• First Submitted: March 1, 2022
• First Submitted That Met QC Criteria: March 1, 2022
• First Posted (Actual): March 10, 2022

Study Record Updates

• Last Update Posted (Actual): August 1, 2024
• Last Update Submitted That Met QC Criteria: July 31, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Ivacaftor; Elexacaftor
• Other Study ID Numbers: VX21-445-124; 2021-005320-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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

Drug and device information, study documents

• 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