Clinical trial NCT03525548: A Study of VX-445 Combination Therapy in CF Subjects Homozygous for F508del (F/F)
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 Homozygous for the F508del Mutation (F/F)
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: 113
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 homozygous for the F508del mutation (F/F)


Eligibility criteria: Key Inclusion Criteria:

* Homozygous for the F508del mutation (F/F)
* 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 Sweat Chloride (SwCl)
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: 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 Week 8)
measure: Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA
timeFrame: Day 1 and Week 4
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: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Hollywood
country: United States
facility: Joe DiMaggio Cystic Fibrosis & Pulmonary Center/ Joe DiMaggio Children's Hospital/ Memorial Regional Hospital
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: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Peoria
country: United States
facility: Saint Francis Medical Center/ Children's Hospital of Illinoise/OSF
state: Illinois
city: New Orleans
country: United States
facility: Tulane Medical Center
state: Louisiana
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: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Chapel Hill
country: United States
facility: UNC Marisco Clinical Research Center
state: North Carolina
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: 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: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
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: 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: Belfast
country: United Kingdom
facility: The Royal Belfast Hospital for Sick Children
city: Birmingham
country: United Kingdom
facility: Heart of England NHS Foundation Trust, Birmingham Heartlands 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: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
References:
citation: Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, Mall MA, Welter JJ, Ramsey BW, McKee CM, Marigowda G, Moskowitz SM, Waltz D, Sosnay PR, Simard C, Ahluwalia N, Xuan F, Zhang Y, Taylor-Cousar JL, McCoy KS; VX17-445-103 Trial Group. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1940-1948. doi: 10.1016/S0140-6736(19)32597-8. Epub 2019 Oct 31.