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

September 26, 2019 updated by: Vertex Pharmaceuticals Incorporated

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)

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

116

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Adelaide, Australia
        • Royal Adelaide Hospital
      • Chermside, Australia
        • Prince Charles Hospital
      • Nedlands, Australia
        • Institute for Respiratory Health Inc./ Sir Charles Gairdner Hospital
      • New Lambton Heights, Australia
        • John Hunter Hospital & Hunter Medical Research Institute
    • Victoria
      • Melbourne, Victoria, Australia
        • The Alfred Hospital
  • Germany
      • Berlin, Germany
        • Charite Paediatric Pulmonology Department
      • Muenchen, Germany
        • Pneumologische Praxis Pasing
  • Ireland
      • Dublin, Ireland
        • St. Vincent's University Hospital
      • Dublin, Ireland
        • Our Lady's Children's Hospital
      • Dublin, Ireland
        • Cork University Hospital
  • Spain
      • Barcelona, Spain
        • Hospital Universitari Vall d Hebron
      • Barcelona, Spain
        • Hospital Universitari Vall d'Hebron Servicio de Broncoscopia
      • Sevilla, Spain
        • Hospital Universitario Virgen del Rocio
  • United Kingdom
      • Cambridge, United Kingdom
        • Papworth Hospital NHS Foundation Trust, Papworth Everard
      • Liverpool, United Kingdom
        • Liverpool Heart and Chest Hospital
      • London, United Kingdom
        • Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
      • Manchester, United Kingdom
        • Wythenshawe Hospital
      • Penarth, United Kingdom
        • University Hospital Llandough
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Yale New Haven Medical Center
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami/Miller School of Medicine
    • Idaho
      • Boise, Idaho, United States, 83712
        • St. Luke's CF Center of Idaho
    • Illinois
      • Niles, Illinois, United States, 60714
        • Advocate Children's Hospital- Park Ridge/ North Suburban Pulmonary and Critical Care Consultants
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana Clinical Research Center, IU Health University Hospital
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • The University of Iowa Hospitals and Clinics
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • The Johns Hopkins Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Helen DeVos Children's Hospital CF Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospital
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine / St. Louis Children's Hospital
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Rutgers-Robert Wood Johnson Medical School
    • New York
      • Albany, New York, United States, 12208
        • Albany Medical College
      • New Hyde Park, New York, United States, 11040
        • Northwell Health, Long Island Jewish Medical Center
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • Syracuse, New York, United States, 13210
        • SUNY Upstate Medical University
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73211
        • Respiratory Diseases of Children and Adolescents
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57105
        • Sanford Research/ USD
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • University of Tennessee Medical Center-Adult Cystic Fibrosis Clinic
      • Memphis, Tennessee, United States, 38103
        • Children's Foundation Research Center/ Le Bonheur Children's Hospital
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah/ Primary Children's Medical Center
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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: IVA
Participants received IVA orally once daily in the evening.
Other Names:
  • VX-770
  • ivacaftor
Drug: TEZ/IVA
Participants received TEZ/IVA orally once daily in the morning.
Other Names:
  • VX-661/VX-770
  • tezacaftor/ivacaftor
Drug: Placebo
Participants received placebo matched TEZ/IVA orally once daily in the morning.
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.
Drug: Placebo
Participants received placebo matched to VX-659/TEZ/IVA orally once daily in the morning.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From Baseline at Week 4

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Absolute Change in Sweat Chloride (SwCl)
Time Frame: From Baseline at Week 4
Sweat samples were collected using an approved collection device.
From Baseline at Week 4
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.
From Baseline at Week 4
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)
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)
Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA
Time Frame: From Day 1 and Week 4
From Day 1 and Week 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vertex Pharmaceuticals Incorporated

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2018

Primary Completion (Actual)

September 26, 2018

Study Completion (Actual)

October 8, 2018

Study Registration Dates

First Submitted

March 1, 2018

First Submitted That Met QC Criteria

March 7, 2018

First Posted (Actual)

March 9, 2018

Study Record Updates

Last Update Posted (Actual)

October 17, 2019

Last Update Submitted That Met QC Criteria

September 26, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VX17-659-103
  • 2017-004133-82 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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