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

Phase 3
Completed
Conditions
Cystic Fibrosis
Interventions
Other: Placebo (matched to ELX/TEZ/IVA)
Other: Placebo (matched to IVA)
Drug: IVA
Registration Number
NCT05274269
Lead Sponsor
Vertex Pharmaceuticals Incorporated
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
307
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo (matched to ELX/TEZ/IVA)Participants received placebo matched to ELX/TEZ/IVA FDC in the morning and placebo matched to IVA in the evening for 24 weeks.
PlaceboPlacebo (matched to IVA)Participants received placebo matched to ELX/TEZ/IVA FDC in the morning and placebo matched to IVA in the evening for 24 weeks.
ELX/TEZ/IVAELX/TEZ/IVAParticipants 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.
ELX/TEZ/IVAIVAParticipants 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.
Primary Outcome Measures
NameTimeMethod
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)From Baseline Through Week 24

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Secondary Outcome Measures
NameTimeMethod
Absolute Change in Sweat Chloride (SwCl)From Baseline Through Week 24

Sweat samples were collected using an approved collection device.

Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain (RD) ScoreFrom Baseline Through Week 24

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.

Absolute Change in Body Mass Index (BMI)From Baseline at Week 24

BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).

Absolute Change in WeightFrom Baseline at Week 24
Number of Pulmonary Exacerbations (PEx)From Baseline Through Week 24

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.

Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)Day 1 up to Week 28

Trial Locations

Locations (90)

McGill University Health Centre, Glen Site, Montreal Children's Hospital

🇨🇦

Montreal, Canada

Fakultni nemocnice v Motole

🇨🇿

Praha 5, Czechia

Hopital Cochin

🇫🇷

Paris, France

Centre Hospitalier Lyon Sud

🇫🇷

Pierre-Bénite, France

Hopital Arnaud de Villeneuve

🇫🇷

Montpellier Cedex 5, France

Oslo University Hospital, Department of Paediatric Medicine

🇳🇴

Oslo, Norway

Cliniques Universitaires de Bruxelles Hopital Erasme

🇧🇪

Brussels, Belgium

Universitair Ziekenhuis Brussel - Campus Jette

🇧🇪

Brussels, Belgium

HagaZiekenhuis van den Haag

🇳🇱

Den Haag, Netherlands

Institute of Tuberculosis and Lung Diseases

🇵🇱

Rabka-Zdrój, Poland

Universitair Ziekenhuis Gent

🇧🇪

Gent, Belgium

Academisch Medisch Centrum (Academic Medical Centre)

🇳🇱

Amsterdam, Netherlands

Hospital Sao Joao

🇵🇹

Porto, Portugal

Kinderspital Zuerich

🇨🇭

Zurich, Switzerland

Cliniques Universitaires Saint-Luc

🇧🇪

Woluwe-Saint-Lambert, Belgium

Universitair Ziekenhuis Antwerpen (UZA) - Antwerp University Hospital

🇧🇪

Edegem, Belgium

Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg

🇧🇪

Leuven, Belgium

Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer

🇮🇹

Firenze, Italy

Malattie Apparato Respiratorio 2 - Centro Fibrosi Cistica

🇮🇹

Orbassano, Italy

Hopital Necker, Enfants Malades

🇫🇷

Paris Cedex 15, France

Sahlgrenska Universitetssjukhuset

🇸🇪

Göteborg, Sweden

Pneumologisches Studienzentrum Muenchen-West

🇩🇪

Muenchen, Germany

Universitätsklinikum Tübingen Klinik für Kinder- und Jugendmedizin

🇩🇪

Tuebingen, Germany

Klinikum Innenstadt, University of Munich

🇩🇪

München, Germany

Stollery Children's Hospital

🇨🇦

Edmonton, Canada

The Hospital for Sick Children

🇨🇦

Toronto, Canada

St. Paul's Hospital

🇨🇦

Vancouver, Canada

Centre Hospitalier de l'Universite de Montreal (CHUM) Hotel-Dieu

🇨🇦

Montreal, Canada

British Columbia Children's Hospital

🇨🇦

Vancouver, Canada

Klinika Detskych Infekcnich Nemoci

🇨🇿

Brno, Czechia

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

Centre Hospitalier Universitaire De Nantes - G. R. Laennec

🇫🇷

Nantes, France

Centre Hospitalier Universitaire (CHU) de Nice - Hopital Pasteur

🇫🇷

Nice, France

Hopital Haut-Leveque - CRCM Adulte

🇫🇷

Pessac, France

Centre Hospitalier Universitaire De Reims, Hopital Sebastopol

🇫🇷

Reims, France

Hopital Robert Debre

🇫🇷

Paris, France

CHU de Rennes - Hôpital Sud

🇫🇷

Rennes, France

Centre de Perharidy

🇫🇷

Roscoff Cedex, France

CHU de Toulouse - Hopital Larre

🇫🇷

Toulouse, France

Hopital Bretonneau

🇫🇷

Tours, France

Charite Paediatric Pulmonology Department

🇩🇪

Berlin, Germany

Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen

🇩🇪

Essen, Germany

Johann Wolfgang Goethe University

🇩🇪

Frankfurt, Germany

Universitätsklinikum Halle (Saale) / Universitätsklinik und Poliklinik für Innere Medizin, Schwerpunkt Pneumologie

🇩🇪

Halle, Germany

Justus-Liebig-Universität Gießen Zentrum für Kinderheilkunde und Jugendmedizin

🇩🇪

Gießen, 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

Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital

🇩🇪

Erlangen, Germany

Dr. von Haunersches Kinderspital

🇩🇪

München, Germany

Klinik fur Kinder- und Jugendmedizin, Universitatsklinikum Munster

🇩🇪

Münster, Germany

Klinikum Westbrandenburg (CF)

🇩🇪

Potsdam, Germany

Universitätsklinikum Ulm, Klinik für Kinder- und Jugendmedizin (CF)

🇩🇪

Ulm, Germany

Universitätsklinikum Würzburg

🇩🇪

Würzburg, Germany

Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona

🇮🇹

Ancona, Italy

National Koranyi Institute for TBC and Pulmonology

🇭🇺

Budapest, Hungary

IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico

🇮🇹

Genova, Italy

Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena

🇮🇹

Milan, Italy

Azienda Ospedaliera Universitaria Policlinico G. Martino

🇮🇹

Messina, Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

🇮🇹

Milano, Italy

Ospedale Pediatrico Bambino Gesu

🇮🇹

Rome, Italy

Azienda Ospedaliera Universitaria Federico II (Adults)

🇮🇹

Naples, Italy

Centro Regionale Fibrosi Cistica, A.O. Ospedale San Carlo

🇮🇹

Potenza, Italy

Azienda Ospedaliera di Verona - Ospedale Civile Maggiore

🇮🇹

Verona, Italy

UMC St. Radboud

🇳🇱

Nijmegen, Netherlands

Erasmus Medical Center

🇳🇱

Rotterdam, Netherlands

Universitair Medisch Centrum Utrecht

🇳🇱

Utrecht, Netherlands

Pediatric Hospital Polanki named of Maciej Płażyński

🇵🇱

Gdańsk, Poland

Hospital de Santa Maria

🇵🇹

Lisbon, Portugal

Instytut Matki i Dziecka, Klinika Mukowiscydozy IMiD, Oddział Chorób Płuc SZPZOZ im.Dzieci Warszawy w Dziekanowie Leśnym

🇵🇱

Łomianki, Poland

Hospital Saint Joan de Deu

🇪🇸

Barcelona, Spain

Hospital de Cruces

🇪🇸

Barakaldo, Spain

Hospital Universitari Vall d Hebron

🇪🇸

Barcelona, Spain

Hospital Universitario de Jerez de la Frontera

🇪🇸

Jerez De La Frontera, Spain

Hospital Infantil Universitario Nino Jesus

🇪🇸

Madrid, Spain

Hospital Universitario Ramon y Cajal

🇪🇸

Madrid, Spain

Hospital Universitari Vall d´Hebron Servicio de Broncoscopia

🇪🇸

Barcelona, Spain

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Hospital Universitario Infantil La Paz

🇪🇸

Madrid, Spain

Corporacio Sanitaria Parc Tauli - Sabadell Hospital Universitari

🇪🇸

Sabadell, Spain

Hospital Universitario Virgen del Rocio

🇪🇸

Sevilla, Spain

Hospital Virgen de la Arrixaca

🇪🇸

Murcia, Spain

Hospital Universitario y Politecnico La Fe

🇪🇸

Valencia, Spain

Karolinska Universitetssjukhuset, Huddinge

🇸🇪

Stockholm, Sweden

Medizinische Universität Innsbruck

🇦🇹

Innsbruck, Austria

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