Clinical trial NCT03525574: A 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 Homozygous or Heterozygous for the F508del Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2018-05-15
Enrollment: 507
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: The study evaluates the long-term safety and tolerability of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous or heterozygous for the F508del mutation


Eligibility criteria: Inclusion Criteria:

* Completed study drug treatment in a parent study i.e.VX17-445-102 (NCT03525444) and VX17-445-103 (NCT03525548); or had study drug interruption(s) in a parent study but completed study visits up to the last scheduled visit of the Treatment Period in the parent study.

Exclusion Criteria:

* History of drug intolerance in a parent study that would pose an additional risk to the subject in the opinion of the investigator.
* Current participation in an investigational drug trial (other than a parent study)

Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Treatment Period: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From Day 1 up to Week 196
Secondary outcomes:
measure: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 102/105 Efficacy Set
timeFrame: From Baseline at Week 192
measure: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/105 Efficacy Set
timeFrame: From Baseline at Week 192
measure: Absolute Change in Sweat Chloride (SwCl) for 102/105 Efficacy Set
timeFrame: From Baseline at Week 192
measure: Absolute Change in Sweat Chloride (SwCl) for 103/105 Efficacy Set
timeFrame: From Baseline at Week 192
measure: Number of Pulmonary Exacerbations (PEx) for 102/105 Efficacy Set
timeFrame: From Baseline at Week 192
measure: Number of Pulmonary Exacerbations (PEx) for 103/105 Efficacy Set
timeFrame: From Baseline at Week 192
measure: Time to First PEx for 102/105 Efficacy Set
timeFrame: From Baseline at Week 192
measure: Time to First PEx for 103/105 Efficacy Set
timeFrame: From Baseline at Week 192
measure: Absolute Change in Body Mass Index (BMI) for 102/105 Efficacy Set
timeFrame: From Baseline at Week 192
measure: Absolute Change in Body Mass Index (BMI) for 103/105 Efficacy Set
timeFrame: From Baseline at Week 192
measure: Absolute Change in BMI Z-score for 102/105 Efficacy Set
timeFrame: From Baseline at Week 192
measure: Absolute Change in BMI Z-score for 103/105 Efficacy Set
timeFrame: From Baseline at Week 192
measure: Absolute Change in Body Weight for 102/105 Efficacy Set
timeFrame: From Baseline at Week 192
measure: Absolute Change in Body Weight for 103/105 Efficacy Set
timeFrame: From Baseline at Week 192
measure: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 102/105 Efficacy Set
timeFrame: From Baseline at Week 192
measure: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/105 Efficacy Set
timeFrame: From Baseline at Week 192
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Banner University of Arizona Medical Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Long Beach
country: United States
facility: Miller Children's Hospital / Long Beach Memorial
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Madera
country: United States
facility: Valley Children's Hospital
state: California
city: Oakland
country: United States
facility: Kaiser Permanente
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Gateway Medical Center
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Gainesville
country: United States
facility: University of Florida, Shands Hospital
state: Florida
city: Hollywood
country: United States
facility: Joe DiMaggio Cystic Fibrosis & Pulmonary Center
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Specialty Care
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary Group, PA
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital Cardiac and Lung Transplant Clinic
state: Florida
city: Atlanta
country: United States
facility: Children's Specialty Services at North Druid Hills
state: Georgia
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert Lurie Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Peoria
country: United States
facility: Cystic Fibrosis Center, Children's Hospital of Illinois at OSF Saint Francis Medical Center
state: Illinois
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
city: New Orleans
country: United States
facility: Tulane Medical Center
state: Louisiana
city: Portland
country: United States
facility: Maine Medical Partners
state: Maine
city: Boston
country: United States
facility: Massachusetts General Hospital Cystic Fibrosis Center Clinical Research Center
state: Massachusetts
city: Detroit
country: United States
facility: Harper University Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota
state: Minnesota
city: Billings
country: United States
facility: Billings Clinic Hospital
state: Montana
city: Omaha
country: United States
facility: Nebraska Medical Center
state: Nebraska
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: UNM Clinical and Translational Science Center
state: New Mexico
city: New York
country: United States
facility: The Cystic Fibrosis Center, Mount Sinai Beth Israel
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Chapel Hill
country: United States
facility: UNC Marsico Clinical Research Center
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
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: Dayton
country: United States
facility: Dayton 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: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Austin
country: United States
facility: Dell Children's Medical Center of Central Texas
state: Texas
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
city: Colchester
country: United States
facility: Vermont Lung Center
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Primary Care Center
state: Virginia
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
city: Richmond
country: United States
facility: Children's Hospital of Richmond at VCU, Children's Pavilion
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin Hospitals and Clinics
state: Wisconsin
city: Milwaukee
country: United States
facility: CTSI Adult Translational Research Unit/Medical College of Wisconsin/Froedtert Hospital
state: Wisconsin
city: North Adelaide
country: Australia
facility: Women & Children's Hospital
city: Parkville
country: Australia
facility: The Royal Children's Hospital
city: South Brisbane
country: Australia
facility: Mater Misericordiae Ltd
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
city: Westmead
country: Australia
facility: Westmead Hospital
city: Graz
country: Austria
facility: University of Graz
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Salzburg
country: Austria
facility: LKH - Universitätsklinikum der PMU Salzburg
city: Vienna
country: Austria
facility: Medizinische Universitat Wien
city: Brussels
country: Belgium
facility: Cliniques Universitaires de Bruxelles Hopital Erasme
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel - Campus Jette
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
city: Calgary
country: Canada
facility: University of Calgary Medical Clinic of the Foothills Medical Centre
city: Montreal
country: Canada
facility: McGill University Health Centre, Glen Site, Montreal Children's Hospital
city: Quebec City
country: Canada
facility: Centre Hospitalier De L'Universite Laval
city: Toronto
country: Canada
facility: The Hospital for Sick Children
city: Vancouver
country: Canada
facility: British Columbia's Children's Hospital
city: Vancouver
country: Canada
facility: St. Paul's Hospital
city: Brno
country: Czechia
facility: Fakultni Nemocnice Brno
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Bordeaux cedex
country: France
facility: Groupe Hospitaler Pellegrin, CHU De Bordeaux
city: Marseille
country: France
facility: CHU Marseille - Hopital Nord
city: Nice
country: France
facility: CHU de Nice - Hopital Pasteur
city: Paris
country: France
facility: Hopital Cochin
city: Rouen
country: France
facility: CHU de Rouen - Hopital Charles Nicolle
city: Suresnes
country: France
facility: Hopital Foch (Suresnes), Hopital Foch, Adultes
city: Erlangen
country: Germany
facility: Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital
city: Giessen
country: Germany
facility: Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin
city: Hannover
country: Germany
facility: Hannover Medical School
city: Mainz
country: Germany
facility: Johannes Gutenberg-Universitaet
city: München
country: Germany
facility: Dr. von Haunersches Kinderspital
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin
city: Wurzburg
country: Germany
facility: University Hospital Wuerzburg
city: Maroussi
country: Greece
facility: General Hospital of Attika "Sismanoglio"(Adult CF center, NHS)
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospendali Riuniti
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer
city: Genova
country: Italy
facility: IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico G. Martino
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Potenza
country: Italy
facility: Centro Regionale Fibrosi Cistica, A.O. Ospedale San Carlo
city: Verona
country: Italy
facility: Azienda Ospedaliera di Verona-Ospedale Civile Maggiore
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Den Haag
country: Netherlands
facility: HagaZiekenhuis van den Haag
city: Heidelberglaan
country: Netherlands
facility: University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
city: Nijmegen
country: Netherlands
facility: UMC St. Radboud
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset, Huddinge
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Birmingham
country: United Kingdom
facility: Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: London
country: United Kingdom
facility: King's College Hospital
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's 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.