Clinical trial NCT03447249: A Phase 3 Study of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
Official title: A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2018-02-27
Enrollment: 385
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy of VX-659 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a minimal function mutation (F/MF subjects).


Eligibility criteria: Key Inclusion Criteria:

* Heterozygous for F508del and an MF mutation (as defined in the protocol)
* Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height

Key Exclusion Criteria:

* Clinically significant cirrhosis with or without portal hypertension
* Lung infection with organisms associated with a more rapid decline in pulmonary status
* Solid organ or hematological transplantation

Other protocol defined Inclusion/Exclusion criteria may apply

Primary outcomes:
measure: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
timeFrame: From Baseline at Week 4
Secondary outcomes:
measure: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
timeFrame: From Baseline through Week 24
measure: Number of Pulmonary Exacerbations (PEx)
timeFrame: From Baseline through Week 24
measure: Absolute Change in Sweat Chloride (SwCl)
timeFrame: From Baseline through Week 24
measure: Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score
timeFrame: From Baseline through Week 24
measure: Absolute Change in Body Mass Index (BMI)
timeFrame: From Baseline at Week 24
measure: Absolute Change in Sweat Chloride
timeFrame: From Baseline at Week 4
measure: Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score
timeFrame: From Baseline at Week 4
measure: Time-to-first Pulmonary Exacerbation (PEx)
timeFrame: From Baseline through Week 24
measure: Absolute Change in BMI Z-score for Participants <=20 Years of Age at Baseline
timeFrame: From Baseline at Week 24
measure: Absolute Change in Body Weight
timeFrame: From Baseline at Week 24
measure: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 28 weeks)
measure: Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, and IVA
timeFrame: Pre-dose on Week 4, 8, 12, and 16
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 Health
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: Arnold Palmer Hospital
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: Kentucky Clinic
state: Kentucky
city: Louisville
country: United States
facility: Kosair Charities Pediatric Clinical Research Unit
state: Kentucky
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital CF 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: 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: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center, Lebanon
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: Lung and Cystic Fibrosis Center at Women and Children's Hospital of Buffalo
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 Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Respiratory Diseases of Children and Adolescents
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 University of Pittsburgh Medical Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Research/ USD
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: Baylor College of Medicine
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 & Allergy/Immunology Clinic
state: Washington
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Chermside
country: Australia
facility: Prince Charles Hospital
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hospital
city: Nedlands
country: Australia
facility: Institute for Respiratory Health Inc./ Sir Charles Gairdner Hospital
city: New Lambton Heights
country: Australia
facility: John Hunter Hospital & Hunter Medical Research Institute
city: Randwick
country: Australia
facility: Sydney Children's Hospital, Randwick
city: Subiaco
country: Australia
facility: Princess Margaret Hospital for Children
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Center
state: Nova Scotia
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: University Hospital Cologne
city: Lubeck
country: Germany
facility: Universitatsklinikum Schleswig-Holstein, Klinik fur Kinder- und Jugendmedizin
city: Muenchen
country: Germany
facility: Pneumologische Praxis Pasing
city: München
country: Germany
facility: Klinikum Innenstadt, University of Munich
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: Children's University Hospital Temple Street
city: Dublin
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Our Lady's Children's Hospital
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital
city: Galway
country: Ireland
facility: National University of Ireland
city: Limerick
country: Ireland
facility: University Hospital Limerick
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Haifa
country: Israel
facility: Pediatric Pulmonary Unit Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Organization
city: Petah tikva
country: Israel
facility: Schneider Children's Medical Center
city: Tel HaShomer
country: Israel
facility: Sheba Medical Center
city: Warsaw
country: Poland
facility: Instytut Matki i Dziecka
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: Coporacio Sanitaria Parc Tauli
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: Zürich
country: Switzerland
facility: Universitaetsspital Zuerich
city: Cambridge
country: United Kingdom
facility: Papworth Hospital NHS Foundation Trust, Papworth Everard
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
city: Leeds
country: United Kingdom
facility: The Leeds Teaching Hospitals NHS Trust, 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: 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: Nottingham University Hospitals NHS Trust, Queens Medical Center
city: Penarth
country: United Kingdom
facility: University Hospital Llandough
Study officials:
References: