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

• ClinicalTrials.gov Identifier: NCT03460990
• Recruitment Status: Completed
• First Posted: March 9, 2018
• Results First Posted: October 17, 2019
• Last Update Posted: October 17, 2019
• Sponsor: Vertex Pharmaceuticals Incorporated
• Information provided by (Responsible Party): Vertex Pharmaceuticals Incorporated

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: VX-659/TEZ/IVA; Drug: TEZ/IVA; Drug: IVA; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: May 1, 2018
• Actual Primary Completion Date: September 26, 2018
• Actual Study Completion Date: October 8, 2018

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: TEZ/IVA; Following a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period.	Drug: TEZ/IVA; Participants received TEZ/IVA orally once daily in the morning.; Other Names: VX-661/VX-770; tezacaftor/ivacaftor; Drug: IVA; Participants received IVA orally once daily in the evening.; Other Names: VX-770; ivacaftor; Drug: Placebo; Participants received placebo matched to VX-659/TEZ/IVA orally once daily in the morning.
Experimental: VX-659/TEZ/IVA TC; Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.	Drug: VX-659/TEZ/IVA; Participants received VX-659/TEZ/IVA orally once daily in the morning.; Other Names: VX-659/VX-661/VX-770; VX-659/tezacaftor/ivacaftor; Drug: IVA; Participants received IVA orally once daily in the evening.; Other Names: VX-770; ivacaftor; Drug: Placebo; Participants received placebo matched TEZ/IVA orally once daily in the morning.

Outcome Measures

Primary Outcome Measures :

1. Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [ Time Frame: From Baseline at Week 4 ]
   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Secondary Outcome Measures :

1. Absolute Change in Sweat Chloride (SwCl) [ Time Frame: From Baseline at Week 4 ]
   Sweat samples were collected using an approved collection device.
2. Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score [ Time Frame: From Baseline at Week 4 ]
   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.
3. Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 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) ]
4. Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA [ Time Frame: From Day 1 and Week 4 ]

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35233

United States, Connecticut

Yale New Haven Medical Center

New Haven, Connecticut, United States, 06511

United States, Florida

University of Miami/Miller School of Medicine

Miami, Florida, United States, 33136

United States, Idaho

St. Luke's CF Center of Idaho

Boise, Idaho, United States, 83712

United States, Illinois

Advocate Children's Hospital- Park Ridge/ North Suburban Pulmonary and Critical Care Consultants

Niles, Illinois, United States, 60714

United States, Indiana

Indiana Clinical Research Center, IU Health University Hospital

Indianapolis, Indiana, United States, 46202

United States, Iowa

The University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States, 52242

United States, Maryland

The Johns Hopkins Hospital

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Boston Children's Hospital

Boston, Massachusetts, United States, 02115

United States, Michigan

Helen DeVos Children's Hospital CF Center

Grand Rapids, Michigan, United States, 49503

United States, Missouri

Children's Mercy Hospital

Kansas City, Missouri, United States, 64108

Washington University School of Medicine / St. Louis Children's Hospital

Saint Louis, Missouri, United States, 63110

United States, New Jersey

Rutgers-Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States, 08901

United States, New York

Albany Medical College

Albany, New York, United States, 12208

Northwell Health, Long Island Jewish Medical Center

New Hyde Park, New York, United States, 11040

Columbia University Medical Center

New York, New York, United States, 10032

SUNY Upstate Medical University

Syracuse, New York, United States, 13210

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

United States, Oklahoma

Respiratory Diseases of Children and Adolescents

Oklahoma City, Oklahoma, United States, 73211

United States, Oregon

Oregon Health & Science University

Portland, Oregon, United States, 97239

United States, Pennsylvania

Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States, 15224

United States, South Dakota

Sanford Research/ USD

Sioux Falls, South Dakota, United States, 57105

United States, Tennessee

University of Tennessee Medical Center-Adult Cystic Fibrosis Clinic

Knoxville, Tennessee, United States, 37920

Children's Foundation Research Center/ Le Bonheur Children's Hospital

Memphis, Tennessee, United States, 38103

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

United States, Texas

Baylor College of Medicine

Houston, Texas, United States, 77030

United States, Utah

University of Utah/ Primary Children's Medical Center

Salt Lake City, Utah, United States, 84132

United States, Washington

Seattle Children's Hospital

Seattle, Washington, United States, 98105

Australia, Victoria

The Alfred Hospital

Melbourne, Victoria, Australia

Australia

Royal Adelaide Hospital

Adelaide, Australia

Prince Charles Hospital

Chermside, Australia

Institute for Respiratory Health Inc./ Sir Charles Gairdner Hospital

Nedlands, Australia

John Hunter Hospital & Hunter Medical Research Institute

New Lambton Heights, Australia

Germany

Charite Paediatric Pulmonology Department

Berlin, Germany

Pneumologische Praxis Pasing

Muenchen, Germany

Ireland

Cork University Hospital

Dublin, Ireland

Our Lady's Children's Hospital

Dublin, Ireland

St. Vincent's University Hospital

Dublin, Ireland

Spain

Hospital Universitari Vall d Hebron

Barcelona, Spain

Hospital Universitari Vall d'Hebron Servicio de Broncoscopia

Barcelona, Spain

Hospital Universitario Virgen del Rocio

Sevilla, Spain

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 Kingdom

Sponsors and Collaborators

Vertex Pharmaceuticals Incorporated

  Study Documents (Full-Text)

Documents provided by Vertex Pharmaceuticals Incorporated:

Study Protocol  [PDF] April 27, 2018

Statistical Analysis Plan  [PDF] June 7, 2018

More Information

• Responsible Party: Vertex Pharmaceuticals Incorporated
• ClinicalTrials.gov Identifier: NCT03460990
• Other Study ID Numbers: VX17-659-103; 2017-004133-82 ( EudraCT Number )
• First Posted: March 9, 2018
• Results First Posted: October 17, 2019
• Last Update Posted: October 17, 2019
• Last Verified: September 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; VX-659; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Ivacaftor; Chloride Channel Agonists; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action