Clinical trial NCT04058353: A Phase 3 Study of VX-445 Combination Therapy in Cystic Fibrosis (CF) Subjects Heterozygous for F508del and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)
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 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: 271
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, safety 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 F508del and a gating or residual function mutation (F/G and F/RF genotypes).


Eligibility criteria: Key Inclusion Criteria:

* Subject has a confirmed diagnosis of CF and is heterozygous for F508del and either a gating or residual function mutation (F/G and F/RF genotypes)
* 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) for ELX/TEZ/IVA Group
timeFrame: From Baseline Through Week 8
Secondary outcomes:
measure: Absolute Change in Sweat Chloride (SwCl) for ELX/TEZ/IVA Group
timeFrame: From Baseline Through Week 8
measure: Absolute Change in ppFEV1 for the ELX/TEZ/IVA Group Compared to the Control Group
timeFrame: From Baseline Through Week 8
measure: Absolute Change in SwCl for ELX/TEZ/IVA Group Compared to the Control Group
timeFrame: From Baseline Through Week 8
measure: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for ELX/TEZ/IVA Group
timeFrame: From Baseline Through Week 8
measure: Absolute Change in CFQ-R Respiratory Domain Score for ELX/TEZ/IVA Group Compared to the Control Group
timeFrame: From Baseline Through Week 8
measure: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
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: Iowa City
country: United States
facility: The University of Iowa Hospitals and Clinics
state: Iowa
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: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
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: 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, VIC
country: Australia
facility: Alfred Hospital
city: Nedlands
country: Australia
facility: Perth Children's Hospital
city: Parkville, VIC
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: Edmonton
country: Canada
facility: Stollery Children's Hospital
city: Québec
country: Canada
facility: McGill University Health Center
city: Toronto
country: Canada
facility: St. Michael's Hospital
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: Erlangen
country: Germany
facility: Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital
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: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital
city: Limerick
country: Israel
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: Orbassano
country: Italy
facility: Malattie Apparato Respiratorio 2 - Fibrosi Cistica
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Gesu
city: Verona
country: Italy
facility: Azienda Ospedaliera di Verona-Ospedale Civile Maggiore
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: 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: Barry PJ, Mall MA, Alvarez A, Colombo C, de Winter-de Groot KM, Fajac I, McBennett KA, McKone EF, Ramsey BW, Sutharsan S, Taylor-Cousar JL, Tullis E, Ahluwalia N, Jun LS, Moskowitz SM, Prieto-Centurion V, Tian S, Waltz D, Xuan F, Zhang Y, Rowe SM, Polineni D; VX18-445-104 Study Group. Triple Therapy for Cystic Fibrosis Phe508del-Gating and -Residual Function Genotypes. N Engl J Med. 2021 Aug 26;385(9):815-825. doi: 10.1056/NEJMoa2100665.