Clinical trial NCT04058366: Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2019-08-15
Enrollment: 251
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From Baseline up to Week 100
Secondary outcomes:
measure: Part A: Absolute Change From Parent Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
timeFrame: From Baseline at Week 96
measure: Part A: Absolute Change From Parent Study Baseline in Sweat Chloride (SwCl)
timeFrame: From Baseline at Week 96
measure: Part A: Absolute Change From Parent Study Baseline in Body Mass Index (BMI)
timeFrame: From Baseline at Week 96
measure: Part A: Absolute Change From Parent Study Baseline in BMI Z-score
timeFrame: From Baseline at Week 96
measure: Part A: Absolute Change From Parent Study Baseline in Body Weight
timeFrame: From Baseline at Week 96
measure: Part A: Absolute Change From Parent Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
timeFrame: From Baseline at Week 96
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Banner University of Arizona Medical Center
state: Arizona
city: Long Beach
country: United States
facility: Miller Children's Hospital / Long Beach Memorial
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco, Lung Transplant Program
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary Group, PA
state: Florida
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital Cystic Fibrosis Center Clinical Rsearch Center
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Medicine
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine / St. Louis Children's Hospital
state: Missouri
city: New York
country: United States
facility: Mount Sinai Beth Israel
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Hospitals
state: North Carolina
city: Cincinnati
country: United States
facility: UC Health Holmes
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Toledo
country: United States
facility: ProMedica Toledo Hospital/Toledo Children's Hospital/Pediatric Pulmonary & Cystic Fibrosis Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Austin
country: United States
facility: Dell Children's Medical Group
state: Texas
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah / Primary Children's Medical Center
state: Utah
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Chermside
country: Australia
facility: The Prince Charles Hospital
city: Melbourne
country: Australia
facility: Alfred Hospital
city: Nedlands
country: Australia
facility: Telethon Kids Institute
city: Parkville
country: Australia
facility: The Royal Children's Hospital
city: South Brisbane
country: Australia
facility: Mater Adult Hospital
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Brussels
country: Belgium
facility: Cliniques Universitaires de Bruxelles Hopital Erasme
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel - Campus Jette
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
city: Montréal
country: Canada
facility: McGill University Health Center
city: Vancouver
country: Canada
facility: St. Paul's Hospital
city: Copenhagen
country: Denmark
facility: Juliane Marie Center, Rigshospitalet
city: Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Bordeaux cedex
country: France
facility: Groupe Hospitaler Pellegrin, CHU De Bordeaux
city: Lille
country: France
facility: CHRU de Lille - Hopital Albert Calmette
city: Marseille
country: France
facility: CHU Marseille - Hopital Nord
city: Montpellier Cedex 5
country: France
facility: CHU de Montpellier - Hopital Arnaud de Villeneuve
city: Paris Cedex 15
country: France
facility: Hopital Necker, Enfants Malades
city: Paris
country: France
facility: Hopital Cochin
city: Rennes Cedex
country: France
facility: Hopital Pontchaillou CHU de Rennes
city: Berlin
country: Germany
facility: Charite Paediatric Pulmonology Department
city: Essen
country: Germany
facility: Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
city: Giessen
country: Germany
facility: Justus-Liebig-Universitaet Gießen Zentrum fur Kinderheilkunde und Jugendmedizin
city: Halle
country: Germany
facility: Universitätsklinikum Halle (Saale) / Universitätsklinik und Poliklinik für Innere Medizin, Schwerpunkt Pneumologie
city: Muenchen
country: Germany
facility: Pneumologisches Studienzentrum Muenchen-West
city: Würzburg
country: Germany
facility: University Hospital Wuerzburg
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: Children's Health Ireland at Crumlin
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital
city: Limerick
country: Ireland
facility: University Hospital Limerick (Adults)
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedale Riuniti
city: Genova
country: Italy
facility: IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Gesu
city: Verona
country: Italy
facility: Azienda Ospedaliera di Verona-Ospedale Civile Maggiore
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Heidelberglaan
country: Netherlands
facility: University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d´Hebron Servicio de Broncoscopia
city: Murcia
country: Spain
facility: Hospital Virgen de la Arrixaca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe
city: Cambridge
country: United Kingdom
facility: Papworth Hospital NHS Foundation Trust, Papworth Everard
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
city: Glasgow
country: United Kingdom
facility: Clinical Research Facility, Queen Elizabeth University Hospital
city: Leeds
country: United Kingdom
facility: St. James University Hospital
city: Liverpool
country: United Kingdom
facility: Liverpool Heart and Chest Hospital
city: London
country: United Kingdom
facility: Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
References:
citation: Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.