Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy

Cystic Fibrosis Clinical Trial

Official title:

A Phase 3, Open-label Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04058366
• Other study ID #: VX18-445-110
• Secondary ID: 2019-000833-37
• Status: Completed
• Phase: Phase 3
• Start date: December 5, 2019
• Est. completion date: December 16, 2022

Study information

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

Clinical Trial Summary

This study evaluated the long-term safety, efficacy, 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 heterozygous for the F508del mutation and a gating or residual function mutation (F/G and F/RF genotypes).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 251
• Est. completion date: December 16, 2022
• Est. primary completion date: December 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Key Inclusion Criteria:

• Completed study drug treatment in parent study (VX18-445-104); or had study drug interruption(s) in parent study but completed study visits up to the last scheduled visit of the Treatment Period in the parent study

Key Exclusion Criteria:

• History of study drug intolerance in parent study

Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

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

Locations

Country	Name	City	State
Australia	The Prince Charles Hospital	Chermside
Australia	Alfred Hospital	Melbourne
Australia	Telethon Kids Institute	Nedlands
Australia	The Royal Children's Hospital	Parkville
Australia	Mater Adult Hospital	South Brisbane
Australia	Queensland Children's Hospital	South Brisbane
Australia	Westmead Hospital	Westmead
Belgium	Cliniques Universitaires de Bruxelles Hopital Erasme	Brussels
Belgium	Universitair Ziekenhuis Brussel - Campus Jette	Brussels
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven
Canada	McGill University Health Center	Montréal
Canada	St. Paul's Hospital	Vancouver
Denmark	Juliane Marie Center, Rigshospitalet	Copenhagen
France	Centre Hospitalier Lyon Sud	Benite Cedex
France	Groupe Hospitaler Pellegrin, CHU De Bordeaux	Bordeaux cedex
France	CHRU de Lille - Hopital Albert Calmette	Lille
France	CHU Marseille - Hopital Nord	Marseille
France	CHU de Montpellier - Hopital Arnaud de Villeneuve	Montpellier Cedex 5
France	Hopital Cochin	Paris
France	Hopital Necker, Enfants Malades	Paris Cedex 15
France	Hopital Pontchaillou CHU de Rennes	Rennes Cedex
Germany	Charite Paediatric Pulmonology Department	Berlin
Germany	Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen	Essen
Germany	Justus-Liebig-Universitaet Gießen Zentrum fur Kinderheilkunde und Jugendmedizin	Giessen
Germany	Universitätsklinikum Halle (Saale) / Universitätsklinik und Poliklinik für Innere Medizin, Schwerpunkt Pneumologie	Halle
Germany	Pneumologisches Studienzentrum Muenchen-West	Muenchen
Germany	University Hospital Wuerzburg	Würzburg
Ireland	Beaumont Hospital	Dublin
Ireland	Children's Health Ireland at Crumlin	Dublin
Ireland	St. Vincent's University Hospital	Dublin
Ireland	University Hospital Limerick (Adults)	Limerick
Italy	Azienda Ospedaliero Universitaria Ospedale Riuniti	Ancona
Italy	IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico	Genova
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	Ospedale Pediatrico Bambino Gesu	Rome
Italy	Azienda Ospedaliera di Verona-Ospedale Civile Maggiore	Verona
Netherlands	Academic Medical Center	Amsterdam
Netherlands	University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis	Heidelberglaan
Spain	Hospital Universitari Vall d´Hebron Servicio de Broncoscopia	Barcelona
Spain	Hospital Virgen de la Arrixaca	Murcia
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitario y Politecnico La Fe	Valencia
United Kingdom	Papworth Hospital NHS Foundation Trust, Papworth Everard	Cambridge
United Kingdom	Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital	Exeter
United Kingdom	Clinical Research Facility, Queen Elizabeth University Hospital	Glasgow
United Kingdom	St. James University Hospital	Leeds
United Kingdom	Liverpool Heart and Chest Hospital	Liverpool
United Kingdom	Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital	London
United Kingdom	Wythenshawe Hospital	Manchester
United Kingdom	Southampton General Hospital	Southampton
United States	Michigan Medicine	Ann Arbor	Michigan
United States	Dell Children's Medical Group	Austin	Texas
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital Cystic Fibrosis Center Clinical Rsearch Center	Boston	Massachusetts
United States	University of North Carolina Hospitals	Chapel Hill	North Carolina
United States	UC Health Holmes	Cincinnati	Ohio
United States	Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	The University of Texas Southwestern Medical Center	Dallas	Texas
United States	National Jewish Health	Denver	Colorado
United States	Texas Children's Hospital	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Kentucky	Lexington	Kentucky
United States	Miller Children's Hospital / Long Beach Memorial	Long Beach	California
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	Columbia University Medical Center	New York	New York
United States	Mount Sinai Beth Israel	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Central Florida Pulmonary Group, PA	Orlando	Florida
United States	Stanford University	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	University of California Davis Medical Center	Sacramento	California
United States	Washington University School of Medicine / St. Louis Children's Hospital	Saint Louis	Missouri
United States	University of Utah / Primary Children's Medical Center	Salt Lake City	Utah
United States	University of California San Francisco, Lung Transplant Program	San Francisco	California
United States	University of Washington Medical Center	Seattle	Washington
United States	ProMedica Toledo Hospital/Toledo Children's Hospital/Pediatric Pulmonary & Cystic Fibrosis Center	Toledo	Ohio
United States	Banner University of Arizona Medical Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  France,  Germany,  Ireland,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)		From Baseline up to Week 100
Secondary	Part A: Absolute Change From Parent Study Baseline 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 at Week 96
Secondary	Part A: Absolute Change From Parent Study Baseline in Sweat Chloride (SwCl)	Sweat samples were collected using an approved collection device.	From Baseline at Week 96
Secondary	Part A: Absolute Change From Parent Study Baseline 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 96
Secondary	Part A: Absolute Change From Parent Study Baseline in BMI Z-score	BMI was defined as weight in kilogram (kg) divided by squared height in meters (m^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.	From Baseline at Week 96
Secondary	Part A: Absolute Change From Parent Study Baseline in Body Weight		From Baseline at Week 96
Secondary	Part A: Absolute Change From Parent Study Baseline in Cystic Fibrosis 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.	From Baseline at Week 96