Clinical trial NCT03525444: A Phase 3 Study of VX-445 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-445 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: 2018-05-15
Enrollment: 405
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-445 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 the F508del mutation (F/MF)
* 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-445, TEZ, M1-TEZ, and IVA
timeFrame: Pre-dose on Week 4, 8, 12, and 16
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/ Children's Hospital of Central California
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/ Joe DiMaggio Children's Hospital/ Memorial Regional Hospital
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
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 Speciality 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: Saint Francis Medical Center/ Children's Hospital of Illinois/OSF
state: Illinois
city: Kansas City
country: United States
facility: 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
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
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: University of New Mexico Clinical & Translational Science Center
state: New Mexico
city: New York
country: United States
facility: 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: University Hospitals Cleveland Medical Center/ Rainbow Babies and Children's Hospital
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: Austin Children's Chest Associates
state: Texas
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
city: Tyler
country: United States
facility: The University of Texas Health Science Center at Tyler
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 Adult Hospital
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 Universitat 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 Gathuisberg
city: Vancouver
country: Canada
facility: British Columbia's Children's Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Montréal
country: Canada
facility: McGill University Health Centre, Glen Site, Montreal Children's Hospital
state: Quebec
city: Calgary
country: Canada
facility: University of Calgary Medical Clinic of the Foothills Medical Centre
city: Qubec
country: Canada
facility: Centre Hospitalier De L'Universite Laval
city: Saint John
country: Canada
facility: Saint John Regional Hospital
city: Toronto
country: Canada
facility: The Hospital for Sick Children
city: Victoria
country: Canada
facility: Vancouver Island Health Authority
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 Cedex, Seine Maritime
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: Heidelberg
country: Germany
facility: Heidelberg Cystic Fibrosis Center
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: Wuerzburg
country: Germany
facility: University Hospital Wuerzburg
city: Maroúsi
country: Greece
facility: General Hospital of Attika "Sismanoglio"(Adult CF center, NHS)
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedale 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 Univeritetssjukhuset, Huddinge
city: Belfast
country: United Kingdom
facility: The Royal Belfast Hospital for Sick Children
city: Brimingham
country: United Kingdom
facility: Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
city: Edinburgh
country: United Kingdom
facility: Royal Hospital for Sick Children
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: Middleton PG, Mall MA, Drevinek P, Lands LC, McKone EF, Polineni D, Ramsey BW, Taylor-Cousar JL, Tullis E, Vermeulen F, Marigowda G, McKee CM, Moskowitz SM, Nair N, Savage J, Simard C, Tian S, Waltz D, Xuan F, Rowe SM, Jain R; VX17-445-102 Study Group. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019 Nov 7;381(19):1809-1819. doi: 10.1056/NEJMoa1908639. Epub 2019 Oct 31.