A Study Evaluating the Safety and Efficacy of VX-659 Combination Therapy in Subjects With Cystic Fibrosis
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
2 other identifiers
interventional
124
4 countries
47
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Aug 2017
Shorter than P25 for phase_2
47 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 18, 2017
CompletedFirst Posted
Study publicly available on registry
July 21, 2017
CompletedStudy Start
First participant enrolled
August 8, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 28, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
February 28, 2018
CompletedResults Posted
Study results publicly available
April 22, 2021
CompletedApril 22, 2021
February 1, 2021
7 months
July 18, 2017
February 25, 2021
March 29, 2021
Conditions
Outcome Measures
Primary Outcomes (2)
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Day 1 Through Safety Follow-up (up to Day 61 for Part 1, Day 85 for Part 2 and Day 57 for Part 3)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline Through Day 29
Secondary Outcomes (4)
Absolute Change in Sweat Chloride Concentrations
From Baseline Through Day 29
Relative Change in ppFEV1
From Baseline Through Day 29
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
From Baseline at Day 29
Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, IVA, M1-IVA, and VX-561
Pre-dose at Day 15 and Day 29
Study Arms (8)
Part 1: Placebo
PLACEBO COMPARATORParticipants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched TEZ/IVA in washout period for 4 days.
Part 1: VX-659/TEZ/IVA TC - Low Dose
EXPERIMENTALParticipants received VX-659 80 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.
Part 1: VX-659/TEZ/IVA TC - Medium Dose
EXPERIMENTALParticipants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.
Part 1: VX-659/TEZ/IVA TC - High Dose
EXPERIMENTALParticipants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.
Part 2: TEZ/IVA
ACTIVE COMPARATORFollowing run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.
Part 2: VX-659/TEZ/IVA TC
EXPERIMENTALFollowing run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.
Part 3: Placebo
PLACEBO COMPARATORParticipants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks.
Part 3: VX-659/TEZ/VX-561 TC
EXPERIMENTALParticipants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks.
Interventions
Tablet for oral administration.
TEZ/IVA fixed-dose combination tablet for oral administration.
Tablet for oral administration.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (47)
Yale New Haven Hospital
New Haven, Connecticut, 06520, United States
University of Miami/Miller School of Medicine
Miami, Florida, 33136, United States
Advocate Children's Hospital - Park Ridge / North Suburban Pulmonary and Critical Care Consultants
Morton Grove, Illinois, 60053, United States
Indiana University Health
Indianapolis, Indiana, 46202, United States
The University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242, United States
The Johns Hopkins Hospital/ Johns Hopkins Hospital, David Rubenstein Child Health Building
Baltimore, Maryland, 21287, United States
Boston Children's Hospital
Boston, Massachusetts, 02155, United States
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts, 01655, United States
University of Michigan Health System
Ann Arbor, Michigan, 48109, United States
Helen DeVos Children's Hospital CF Center
Grand Rapids, Michigan, 49503, United States
Children's Mercy Hospital
Kansas City, Missouri, 64108, United States
Rutgers-Robert Wood Johnson Medical School/ Rutgers-Robert Wood Johnson Medical School, Clinical Research Center
New Brunswick, New Jersey, 08902, United States
Albany Medical College
Albany, New York, 12208, United States
Northwell Health, Long Island Jewish Medical Center
New Hyde Park, New York, 11040, United States
Columbia University Medical Center
New York, New York, 10032, United States
SUNY Upstate Medical University
Syracuse, New York, 13210, United States
Respiratory Diseases of Children & Adolescents
Oklahoma City, Oklahoma, 73112, United States
Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15224, United States
Sanford Research / USD
Sioux Falls, South Dakota, 57104, United States
University of Tennessee Medical Center-Adult Cystic Fibrosis Clinic
Knoxville, Tennessee, 37920, United States
Children's Foundation Research Center / Le Bonheur Children's Hospital
Memphis, Tennessee, 38103, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
University of Utah / Primary Children's Medical Center
Salt Lake City, Utah, 84014, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Providence Pediatric Pulmonary & Allergy/Immunology Clinic
Spokane, Washington, 99204, United States
Cork University Hospital
Cork, Ireland
St. Vincent's University Hosptial
Dublin, Ireland
Galway University Hospitals
Galway, Ireland
University Hospital Limerick
Limerick, Ireland
Carmel Medical Center
Haifa, Israel
Ruth Children's Hospital Rambam Health Care Campus
Haifa, Israel
Hadassah Medical Organization
Jerusalem, Israel
The Chaim Sheba medical center
Ramat Gan, Israel
Schneider Children's Medical Center
Tikvah, Israel
Birmingham Heartlands Hospital
Birmingham, B95SS, United Kingdom
Papworth Hospital NHS Foundation Trust, Papworth Everard
Cambridge, United Kingdom
University Hospital Llandough in Cardiff
Cardiff, United Kingdom
Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
Devon, United Kingdom
The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
Fulham, United Kingdom
Greater Glasgow and Clyde NHS Board, Glasgow Clinical Research Facility
Glasgow, United Kingdom
Southampton University Hospitals NHS Foundation Trust
Hampshire, United Kingdom
Regional Respiratory Centre Belfast City Hospital
London, United Kingdom
Royal Brompton & Harefied NHS Foundation Trust
London, United Kingdom
University Hospital of South Manchester NHS Trust, North West Lung Centre
Manchester, United Kingdom
Liverpool Heart and Chest Hospital
Merseyside, United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, United Kingdom
Ruth Children's Hospital Rambam Health Care Campus
Nottingham, United Kingdom
Related Publications (3)
Heneghan M, 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. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.
PMID: 37983082DERIVEDSouthern 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.
PMID: 33331662DERIVEDDavies 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.
PMID: 30334693DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Monitor
- Organization
- Vertex Pharmaceuticals Incorporated
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 18, 2017
First Posted
July 21, 2017
Study Start
August 8, 2017
Primary Completion
February 28, 2018
Study Completion
February 28, 2018
Last Updated
April 22, 2021
Results First Posted
April 22, 2021
Record last verified: 2021-02