A Phase 3 Study of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)

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 Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03447249
• Other study ID #: VX17-659-102
• Secondary ID: 2017-004132-11
• Status: Completed
• Phase: Phase 3
• Start date: March 7, 2018
• Est. completion date: February 5, 2019

Study information

• Verified date: March 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-659 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a minimal function mutation (F/MF subjects).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 385
• Est. completion date: February 5, 2019
• Est. primary completion date: February 5, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Key Inclusion Criteria:

• Heterozygous for F508del and an MF mutation (as defined in the protocol)

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

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	Prince Charles Hospital	Chermside
Australia	Royal Brisbane & Women's Hospital	Herston
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
Australia	Sydney Children's Hospital, Randwick	Randwick
Australia	Princess Margaret Hospital for Children	Subiaco
Canada	Stollery Children's Hospital	Edmonton	Alberta
Canada	Queen Elizabeth II Health Sciences Center	Halifax	Nova Scotia
Canada	St. Michael's Hospital	Toronto
Denmark	Juliane Marie Center, Rigshospitalet	Copenhagen
Germany	Charite Paediatric Pulmonology Department	Berlin
Germany	Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen	Essen
Germany	Clinic of J.W Goethe University	Frankfurt
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Mukeviszidose-Zentrum am Universitatsklinikum Jena, Klinik fuer Kinder - und Jugendmedizin	Jena
Germany	University Hospital Cologne	Koeln
Germany	Universitatsklinikum Schleswig-Holstein, Klinik fur Kinder- und Jugendmedizin	Lubeck
Germany	Pneumologische Praxis Pasing	Muenchen
Germany	Klinikum Innenstadt, University of Munich	München
Ireland	Beaumont Hospital	Dublin
Ireland	Children's University Hospital Temple Street	Dublin
Ireland	Cork University Hospital	Dublin
Ireland	Our Lady's Children's Hospital	Dublin
Ireland	St. Vincent's University Hospital	Dublin
Ireland	National University of Ireland	Galway
Ireland	University Hospital Limerick	Limerick
Israel	Lady Davis Carmel Medical Center	Haifa
Israel	Pediatric Pulmonary Unit Rambam Medical Center	Haifa
Israel	Hadassah Medical Organization	Jerusalem
Israel	Schneider Children's Medical Center	Petah tikva
Israel	Sheba Medical Center	Tel HaShomer
Poland	Instytut Matki i Dziecka	Warsaw
Spain	Hospital Universitari Vall d Hebron	Barcelona
Spain	Hospital Universitari Vall d'Hebron Servicio de Broncoscopia	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Infantil La Paz	Madrid
Spain	Coporacio Sanitaria Parc Tauli	Sabadell
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitario y Politecnico La Fe	Valencia
Switzerland	Lindenhofspital - Quartier Bleu	Bern
Switzerland	Kinderspital Zuerich	Zürich
Switzerland	Universitaetsspital Zuerich	Zürich
United Kingdom	Papworth Hospital NHS Foundation Trust, Papworth Everard	Cambridge
United Kingdom	Queen Elizabeth University Hospital	Glasgow
United Kingdom	The Leeds Teaching Hospitals NHS Trust, St. James University Hospital	Leeds
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	The Newcastle Upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary	Newcastle Upon Tyne
United Kingdom	Nottingham University Hospitals NHS Trust, Queens Medical Center	Nottingham
United Kingdom	University Hospital Llandough	Penarth
United States	Albany Medical College	Albany	New York
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Children's Hospital Colorado	Aurora	Colorado
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	Lung and Cystic Fibrosis Center at Women and Children's Hospital of Buffalo	Buffalo	New York
United States	Clinical Research of Charlotte	Charlotte	North Carolina
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Cystic Fibrosis Center of Chicago	Glenview	Illinois
United States	Helen DeVos Children's Hospital CF Center	Grand Rapids	Michigan
United States	Hartford Health	Hartford	Connecticut
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	University of Mississippi Medical Center	Jackson	Mississippi
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	University of Tennessee Medical Center - Adult Cystic Fibrosis Clinic	Knoxville	Tennessee
United States	Dartmouth Hitchcock Medical Center, Lebanon	Lebanon	New Hampshire
United States	Kentucky Clinic	Lexington	Kentucky
United States	Kosair Charities Pediatric Clinical Research Unit	Louisville	Kentucky
United States	Children's Foundation Research Center/ Le Bonheur Children's Hospital	Memphis	Tennessee
United States	Nicklaus Children's Hospital	Miami	Florida
United States	University of Miami/ Miller School of Medicine	Miami	Florida
United States	University of Minnesota	Minneapolis	Minnesota
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	Arnold Palmer Hospital	Orlando	Florida
United States	Stanford University	Palo Alto	California
United States	Drexel University College of Medicine/ Drexel Adult Cystic Fibrosis Center	Philadelphia	Pennsylvania
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	Johns Hopkins All Children's Hospital Outpatient Care Center	Saint Petersburg	Florida
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,  Australia,  Canada,  Denmark,  Germany,  Ireland,  Israel,  Poland,  Spain,  Switzerland,  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 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 Week 24
Secondary	Number of Pulmonary Exacerbations (PEx)	Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.	From Baseline through Week 24
Secondary	Absolute Change in Sweat Chloride (SwCl)	Sweat samples were collected using an approved collection device.	From Baseline through Week 24
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 through Week 24
Secondary	Absolute Change in Body Mass Index (BMI)	BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).	From Baseline at Week 24
Secondary	Absolute Change in Sweat Chloride	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	Time-to-first Pulmonary Exacerbation (PEx)	Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.	From Baseline through Week 24
Secondary	Absolute Change in BMI Z-score for Participants <=20 Years of Age at Baseline	BMI was defined as weight in kg divided by height in m^2. z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI.	From Baseline at Week 24
Secondary	Absolute Change in Body Weight		From Baseline at Week 24
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 28 weeks)
Secondary	Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, and IVA		Pre-dose on Week 4, 8, 12, and 16