A Study of VX-659 Combination Therapy in CF Subjects Homozygous for F508del (F/F)

Cystic Fibrosis Clinical Trial

Official title:

A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del Mutation (F/F)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03460990
• Other study ID #: VX17-659-103
• Secondary ID: 2017-004133-82
• Status: Completed
• Phase: Phase 3
• Start date: May 1, 2018
• Est. completion date: October 8, 2018

Study information

• Verified date: September 2019
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy of VX-659 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: October 8, 2018
• Est. primary completion date: September 26, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• VX-659/TEZ/IVA
Participants received VX-659/TEZ/IVA orally once daily in the morning.
• TEZ/IVA
Participants received TEZ/IVA orally once daily in the morning.
• IVA
Participants received IVA orally once daily in the evening.
• Placebo
Participants received placebo matched TEZ/IVA orally once daily in the morning.
• Placebo
Participants received placebo matched to VX-659/TEZ/IVA orally once daily in the morning.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	Prince Charles Hospital	Chermside
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Institute for Respiratory Health Inc./ Sir Charles Gairdner Hospital	Nedlands
Australia	John Hunter Hospital & Hunter Medical Research Institute	New Lambton Heights
Germany	Charite Paediatric Pulmonology Department	Berlin
Germany	Pneumologische Praxis Pasing	Muenchen
Ireland	Cork University Hospital	Dublin
Ireland	Our Lady's Children's Hospital	Dublin
Ireland	St. Vincent's University Hospital	Dublin
Spain	Hospital Universitari Vall d Hebron	Barcelona
Spain	Hospital Universitari Vall d'Hebron Servicio de Broncoscopia	Barcelona
Spain	Hospital Universitario Virgen del Rocio	Sevilla
United Kingdom	Papworth Hospital NHS Foundation Trust, Papworth Everard	Cambridge
United Kingdom	Liverpool Heart and Chest Hospital	Liverpool
United Kingdom	Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital	London
United Kingdom	Wythenshawe Hospital	Manchester
United Kingdom	University Hospital Llandough	Penarth
United States	Albany Medical College	Albany	New York
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	St. Luke's CF Center of Idaho	Boise	Idaho
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Helen DeVos Children's Hospital CF Center	Grand Rapids	Michigan
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana Clinical Research Center, IU Health University Hospital	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	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Rutgers-Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Yale New Haven Medical Center	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	Advocate Children's Hospital- Park Ridge/ North Suburban Pulmonary and Critical Care Consultants	Niles	Illinois
United States	Respiratory Diseases of Children and Adolescents	Oklahoma City	Oklahoma
United States	Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Washington University School of Medicine / St. Louis Children's Hospital	Saint Louis	Missouri
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	SUNY Upstate Medical University	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Ireland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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 at Week 4
Secondary	Absolute Change in Sweat Chloride (SwCl)	Sweat samples were collected using an approved collection device.	From Baseline at Week 4
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 Week 4
Secondary	Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)		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)
Secondary	Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA		From Day 1 and Week 4