Clinical trial NCT03447262: A Study Evaluating the Long Term Safety and Efficacy of VX-659 Combination Therapy
Official title: A Phase 3, Open-label Study Evaluating the Long Term Safety and Efficacy of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Who Are Homozygous or Heterozygous for the F508del Mutation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2018-02-27
Enrollment: 484
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 will evaluate the long-term safety and tolerability of VX-659 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; 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: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Day 1 up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First in the Current Study 659-105 (up to Week 100)
Secondary outcomes:
measure: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for Participants From the Parent Study 659-102
timeFrame: From Baseline at Week 72 (Study 659-105)
measure: Absolute Change in ppFEV1 for Participants From the Parent Study 659-103
timeFrame: From Baseline at Week 72 (Study 659-105)
measure: Absolute Change in Sweat Chloride (SwCl) for Participants From the Parent Study 659-102
timeFrame: From Baseline at Week 24 (Study 659-105)
measure: Absolute Change in SwCl for Participants From the Parent Study 659-103
timeFrame: From Baseline at Week 24 (Study 659-105)
measure: Number of Pulmonary Exacerbations (PEx) for Participants From the Parent Study 659-102
timeFrame: From Baseline up to Week 96 (Study 659-105)
measure: Number of PEx for Participants From the Parent Study 659-103
timeFrame: From Baseline up to Week 96 (Study 659-105)
measure: Number of Participants With at Least One PEx for Participants From the Parent Study 659-102
timeFrame: From Baseline up to Week 96 (Study 659-105)
measure: Number of Participants With at Least One PEx for Participants From the Parent Study 659-103
timeFrame: From Baseline up to Week 96 (Study 659-105)
measure: Absolute Change in Body Mass Index (BMI) for Participants From the Parent Study 659-102
timeFrame: From Baseline at Week 72 (Study 659-105)
measure: Absolute Change in BMI for Participants From the Parent Study 659-103
timeFrame: From Baseline at Week 72 (Study 659-105)
measure: Absolute Change in BMI Z-score for Participants From the Parent Study 659-102 (Participants <=20 Years Old at Parent Study Baseline)
timeFrame: From Baseline at Week 60 (Study 659-105)
measure: Absolute Change in BMI Z-score for Participants From The Parent Study 659-103 (Participants <=20 Years Old at Parent Study Baseline)
timeFrame: From Baseline at Week 60 (Study 659-105)
measure: Absolute Change in Body Weight for Participants From the Parent Study 659-102
timeFrame: From Baseline at Week 72 (Study 659-105)
measure: Absolute Change in Body Weight for Participants From the Parent Study 659-103
timeFrame: From Baseline at Week 72 (Study 659-105)
measure: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for Participants From the Parent Study 659-102
timeFrame: From Baseline at Week 72 (Study 659-105)
measure: Absolute Change in CFQ-R Respiratory Domain Score for Participants From the Parent Study 659-103
timeFrame: From Baseline at Week 72 (Study 659-105)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale New Haven Medical Center
state: Connecticut
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Orlando Health, Inc.- Arnold Palmer Hospital for Children (APH)
state: Florida
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital Outpatient Care Center
state: Florida
city: Boise
country: United States
facility: St. Luke's CF Center of Idaho
state: Idaho
city: Glenview
country: United States
facility: Cystic Fibrosis Center of Chicago
state: Illinois
city: Niles
country: United States
facility: Advocate Children's Hospital - Park Ridge / North Suburban Pulmonary and Critical Care Consultants
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Clinical Research Center, IU Health University Hospital
state: Indiana
city: Iowa City
country: United States
facility: The University of Iowa Hospitals and Clinics
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Kosair Charities Pediatric Clinical Research Unit
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Medicine
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Medical Group Adult Cystic Fibrosis Care Center
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: The Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine/ St. Louis Children's Hospital
state: Missouri
city: Manchester
country: United States
facility: Dartmouth Hitchcock, Manchester
state: New Hampshire
city: New Brunswick
country: United States
facility: Rutgers-Robert Wood Johnson Medical School
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Buffalo
country: United States
facility: CF Therapeutics Development Center of Western New York
state: New York
city: New Hyde Park
country: United States
facility: Northwell Health, Long Island Jewish Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Charlotte
country: United States
facility: Clinical Research of Charlotte
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Santiago Reyes, M.D.
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Drexel University College of Medicine / Drexel Adult Cystic Fibrosis Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Children's Specialty Clinic
state: South Dakota
city: Knoxville
country: United States
facility: University of Tennessee Medical Center- Adult Cystic Fibrosis Clinic
state: Tennessee
city: Memphis
country: United States
facility: Children's Foundation Research Center / Le Bonheur Children's Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Fort Worth
country: United States
facility: Cook Children's 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: Seattle Children's Hospital
state: Washington
city: Spokane
country: United States
facility: Providence Pediatric Pulmonary & Cystic Fibrosis Clinic
state: Washington
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Chermside
country: Australia
facility: The Prince Charles Hospital
city: Melbourne
country: Australia
facility: Alfred Hospital
city: Nedlands
country: Australia
facility: Institute for Respiratory Health, Sir Charles Gairdner Hospital
city: New Lambton
country: Australia
facility: John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital
city: Perth
country: Australia
facility: Telethon Kids Institute
city: Randwick
country: Australia
facility: Sydney Children's Hospital
city: South Brisbane
country: Australia
facility: Lady Cilento Children's Hospital
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Center
city: Toronto
country: Canada
facility: St. Michael's Hospital
city: Copenhagen
country: Denmark
facility: Juliane Marie Center, Rigshospitalet
city: Berlin
country: Germany
facility: Charite Paediatric Pulmonology Department
city: Essen
country: Germany
facility: Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
city: Frankfurt
country: Germany
facility: Clinic of J.W. Goethe University
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Jena
country: Germany
facility: Mukeviszidose-Zentrum am Universitatsklinikum Jena, Klinik fuer Kinder- und Jugendmedizin
city: Koeln
country: Germany
facility: Universitaetsklinkum Koeln, CF-Studienzentrum
city: Lubeck
country: Germany
facility: Universitatsklinikum Schleswig-Holstein, Klinik für Kinder- und Jugendmedizin
city: Muenchen
country: Germany
facility: Pneumologische Praxis Pasing
city: München
country: Germany
facility: Klinikum Innenstadt, University of Munich
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: Our Lady's Children's Hospital
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital
city: Dublin
country: Ireland
facility: Temple Street Children's University Hospital
city: Galway
country: Ireland
facility: University Hospital Galway
city: Limerick
country: Ireland
facility: University Hospital Limerick
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus, Liver Unit
city: Jerusalem
country: Israel
facility: Pediatrics Hadassah Medical Center
city: Petah Tikva
country: Israel
facility: Schneider Children's Medical Center
city: Tel HaShomer
country: Israel
facility: Sheba Medical Center
city: Łomianki
country: Poland
facility: Klinika Mukowiscydozy IMD Oddozial Chorob Pluc Szpzoz IM. Dzieci WarszaWY
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d´Hebron Servicio de Broncoscopia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Infantil La Paz
city: Sabadell
country: Spain
facility: Parc Tauli Sabadell Hospital Universitari
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe
city: Bern
country: Switzerland
facility: Lindenhofspital - Quartier Bleu
city: Zürich
country: Switzerland
facility: Kinderspital Zuerich
city: Cambridge
country: United Kingdom
facility: Papworth Hospital NHS Foundation Trust, Papworth Everard
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 Head and Chest Hospital
city: London
country: United Kingdom
facility: Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
city: Manchester
country: United Kingdom
facility: Wythenshaw e Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
city: Nottingham
country: United Kingdom
facility: Wolfson Cystic Fibrosis Unit, City Campus
city: Penarth
country: United Kingdom
facility: All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
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.