Clinical trial NCT03224351: A Study Evaluating the Safety and Efficacy of VX-659 Combination Therapy in Subjects With Cystic Fibrosis
Official title: A Phase 2, Randomized, Double-blind, Controlled Study to Evaluate the Safety and Efficacy of VX-659 Combination Therapy in Subjects Aged 18 Years and Older With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2017-07-21
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 2, randomized, double-blind, placebo- and tezacaftor/ivacaftor (TEZ/IVA)-controlled, parallel-group, 3-part, multicenter study designed to evaluate the safety and efficacy of VX-659 in triple combination (TC) with TEZ and IVA in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F/F genotype), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ, IVA, or TEZ/IVA (F/MF genotypes).


Eligibility criteria: Key Inclusion Criteria:

* Body weight ≥35 kg.
* Subjects must have an eligibleCFTR genotype.

  * Part 1 and Part 3: Heterozygous for F508del and an MF mutation (F/MF)
  * Part 2: Homozygous for F508del (F/F)
* FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height

Key Exclusion Criteria:

* History of clinically significant cirrhosis with or without portal hypertension.
* Glucose-6-phosphate dehydrogenase (G6PD) deficiency
* Lung infection with organisms associated with a more rapid decline in pulmonary status.
* History of solid organ or hematological transplantation.

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 (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 Through Safety Follow-up (up to Day 61 for Part 1, Day 85 for Part 2 and Day 57 for Part 3)
measure: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
timeFrame: From Baseline Through Day 29
Secondary outcomes:
measure: Absolute Change in Sweat Chloride Concentrations
timeFrame: From Baseline Through Day 29
measure: Relative Change in ppFEV1
timeFrame: From Baseline Through Day 29
measure: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
timeFrame: From Baseline at Day 29
measure: Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561
timeFrame: Pre-dose at Day 15 and Day 29
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Miami
country: United States
facility: University of Miami/Miller School of Medicine
state: Florida
city: Morton Grove
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 University Health
state: Indiana
city: Iowa City
country: United States
facility: The University of Iowa Hospitals and Clinics
state: Iowa
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital/ Johns Hopkins Hospital, David Rubenstein Child Health Building
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: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: New Brunswick
country: United States
facility: Rutgers-Robert Wood Johnson Medical School/ Rutgers-Robert Wood Johnson Medical School, Clinical Research Center
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College
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: Oklahoma City
country: United States
facility: Respiratory Diseases of Children & Adolescents
state: Oklahoma
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: 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: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: St. Vincent's University Hosptial
city: Galway
country: Ireland
facility: Galway University Hospitals
city: Limerick
country: Ireland
facility: University Hospital Limerick
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Haifa
country: Israel
facility: Ruth Children's Hospital Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Hadassah Medical Organization
city: Ramat Gan
country: Israel
facility: The Chaim Sheba medical center
city: Tikvah
country: Israel
facility: Schneider Children's Medical Center
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Cambridge
country: United Kingdom
facility: Papworth Hospital NHS Foundation Trust, Papworth Everard
city: Cardiff
country: United Kingdom
facility: University Hospital Llandough in Cardiff
city: Devon
country: United Kingdom
facility: Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
city: Fulham
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
city: Glasgow
country: United Kingdom
facility: Greater Glasgow and Clyde NHS Board, Glasgow Clinical Research Facility
city: Hampshire
country: United Kingdom
facility: Southampton University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: Regional Respiratory Centre Belfast City Hospital
city: London
country: United Kingdom
facility: Royal Brompton & Harefied NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: University Hospital of South Manchester NHS Trust, North West Lung Centre
city: Merseyside
country: United Kingdom
facility: Liverpool Heart and Chest Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Nottingham
country: United Kingdom
facility: Ruth Children's Hospital Rambam Health Care Campus
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.
citation: Davies JC, Moskowitz SM, Brown C, Horsley A, Mall MA, McKone EF, Plant BJ, Prais D, Ramsey BW, Taylor-Cousar JL, Tullis E, Uluer A, McKee CM, Robertson S, Shilling RA, Simard C, Van Goor F, Waltz D, Xuan F, Young T, Rowe SM; VX16-659-101 Study Group. VX-659-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. N Engl J Med. 2018 Oct 25;379(17):1599-1611. doi: 10.1056/NEJMoa1807119. Epub 2018 Oct 18.