A Study of VX-445 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-445 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: NCT03525548
• Other study ID #: VX17-445-103
• Secondary ID: 2018-000184-89
• Status: Completed
• Phase: Phase 3
• Start date: August 3, 2018
• Est. completion date: December 28, 2018

Study information

• Verified date: January 2020
• 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-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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 113
• Est. completion date: December 28, 2018
• Est. primary completion date: December 28, 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-445/TEZ/IVA
Participants received VX-445/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 to VX-445/TEZ/IVA orally once daily in the morning.
• Placebo
Participants received placebo matched TEZ/IVA orally once daily in the morning.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires de Bruxelles Hopital Erasme	Brussels
Belgium	Universitair Ziekenhuis Brussel - Campus Jette	Brussels
Belgium	UZ Antwerpen	Edegem
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven
Netherlands	Academic Medical Center	Amsterdam
Netherlands	HagaZiekenhuis van den Haag	Den Haag
Netherlands	University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis	Heidelberglaan
Netherlands	UMC St. Radboud	Nijmegen
Netherlands	Erasmus Medical Center	Rotterdam
United Kingdom	The Royal Belfast Hospital for Sick Children	Belfast
United Kingdom	Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital	Birmingham
United Kingdom	Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital	Exeter
United Kingdom	Leeds General Infirmary	Leeds
United Kingdom	King's College Hospital	London
United Kingdom	Southampton General Hospital	Southampton
United States	Massachusetts General Hospital Cystic Fibrosis Center Clinical Research Center	Boston	Massachusetts
United States	UNC Marisco Clinical Research Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia Primary Care Center	Charlottesville	Virginia
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Vermont Lung Center	Colchester	Vermont
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	The University of Texas Southwestern Medical Center	Dallas	Texas
United States	Dayton Children's Hospital	Dayton	Ohio
United States	National Jewish Health	Denver	Colorado
United States	Harper University Hospital	Detroit	Michigan
United States	Joe DiMaggio Cystic Fibrosis & Pulmonary Center/ Joe DiMaggio Children's Hospital/ Memorial Regional Hospital	Hollywood	Florida
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Miller Children's Hospital/ Long Beach Memorial	Long Beach	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Valley Children's Hospital	Madera	California
United States	West Virginia University	Morgantown	West Virginia
United States	Tulane Medical Center	New Orleans	Louisiana
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Central Florida Pulmonary Group, PA	Orlando	Florida
United States	Nemours Children's Hospital	Orlando	Florida
United States	Saint Francis Medical Center/ Children's Hospital of Illinoise/OSF	Peoria	Illinois
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Tampa General Hospital Cardiac and Lung Transplant Clinic	Tampa	Florida
United States	ProMedica Toledo Hospital/ Toledo Children's Hospital/ Pediatric Pulmonary & Cystic Fibrosis Center	Toledo	Ohio
United States	Banner University of Arizona Medical Center	Tucson	Arizona
United States	New York Medical College	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Belgium,  Netherlands,  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 indicate fewer symptoms and better health-related quality of life.	From Baseline at Week 4
Secondary	Safety and Tolerability as Assessed by 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-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA		Day 1 and Week 4