A Study Evaluating the Safety and Efficacy of VX-659 Combination Therapy in Subjects With Cystic Fibrosis

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03224351
• Other study ID #: VX16-659-101
• Secondary ID: 2016-003585-11
• Status: Completed
• Phase: Phase 2
• Start date: August 8, 2017
• Est. completion date: February 28, 2018

Study information

• Verified date: February 2021
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: February 28, 2018
• Est. primary completion date: February 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• VX-659
Tablet for oral administration.
• TEZ/IVA
TEZ/IVA fixed-dose combination tablet for oral administration.
• IVA
Tablet for oral administration.
• Placebo (matched to VX-659/TEZ/IVA)
Placebo matched to VX-659 and TEZ/IVA.
• TEZ
Tablet for oral administration.
• VX-561
Tablet for oral administration.
• Placebo (matched to VX-659/TEZ/VX-561)
Placebo matched to VX-659, TEZ and VX-561.

Locations

Country	Name	City	State
Ireland	Cork University Hospital	Cork
Ireland	St. Vincent's University Hosptial	Dublin
Ireland	Galway University Hospitals	Galway
Ireland	University Hospital Limerick	Limerick
Israel	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
United Kingdom	Birmingham Heartlands Hospital	Birmingham
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 States	Albany Medical College	Albany	New York
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	The Johns Hopkins Hospital/ Johns Hopkins Hospital, David Rubenstein Child Health Building	Baltimore	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Helen DeVos Children's Hospital CF Center	Grand Rapids	Michigan
United States	Indiana University Health	Indianapolis	Indiana
United States	The University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	University of Tennessee Medical Center-Adult Cystic Fibrosis Clinic	Knoxville	Tennessee
United States	Children's Foundation Research Center / Le Bonheur Children's Hospital	Memphis	Tennessee
United States	University of Miami/Miller School of Medicine	Miami	Florida
United States	Advocate Children's Hospital - Park Ridge / North Suburban Pulmonary and Critical Care Consultants	Morton Grove	Illinois
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Rutgers-Robert Wood Johnson Medical School/ Rutgers-Robert Wood Johnson Medical School, Clinical Research Center	New Brunswick	New Jersey
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Northwell Health, Long Island Jewish Medical Center	New Hyde Park	New York
United States	Columbia University Medical Center	New York	New York
United States	Respiratory Diseases of Children & Adolescents	Oklahoma City	Oklahoma
United States	Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	University of Utah / Primary Children's Medical Center	Salt Lake City	Utah
United States	Seattle Children's Hospital	Seattle	Washington
United States	Sanford Research / USD	Sioux Falls	South Dakota
United States	Providence Pediatric Pulmonary & Allergy/Immunology Clinic	Spokane	Washington
United States	SUNY Upstate Medical University	Syracuse	New York
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Ireland,  Israel,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Absolute Change in Sweat Chloride Concentrations	Sweat samples were collected using an approved collection device.	From Baseline Through Day 29
Secondary	Relative Change in 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	Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.	From Baseline at Day 29
Secondary	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