A Phase 3 Study of VX-445 Combination Therapy in Cystic Fibrosis (CF) Subjects Heterozygous for F508del and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)

June 11, 2021 updated by: Vertex Pharmaceuticals Incorporated

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 Heterozygous for the F508del Mutation and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)

This study will evaluate the efficacy, safety and pharmacodynamics of elexacaftor (ELX, VX-445) in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a gating or residual function mutation (F/G and F/RF genotypes).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

271

Phase

  • Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

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
      • Chermside, Australia
        • The Prince Charles Hospital
      • Melbourne, VIC, Australia
        • Alfred Hospital
      • Nedlands, Australia
        • Perth Children's Hospital
      • Parkville, VIC, Australia
        • The Royal Children's Hospital
      • South Brisbane, Australia
        • Queensland CHILDREN'S HOSPITAL
      • South Brisbane, Australia
        • Mater Adult Hospital
      • Westmead, Australia
        • Westmead Hospital
  • Belgium
      • Brussels, Belgium
        • Universitair Ziekenhuis Brussel - Campus Jette
      • Brussels, Belgium
        • Cliniques Universitaires de Bruxelles Hopital Erasme
      • Gent, Belgium
        • Universitair Ziekenhuis Gent
      • Leuven, Belgium
        • Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
  • Canada
      • Edmonton, Canada
        • Stollery Children's Hospital
      • Québec, Canada
        • McGill University Health Center
      • Toronto, Canada
        • St. Michael's Hospital
      • Vancouver, Canada
        • St. Paul's Hospital
  • Denmark
      • Copenhagen, Denmark
        • Juliane Marie Center, Rigshospitalet
  • France
      • Benite Cedex, France
        • Centre Hospitalier Lyon Sud
      • Bordeaux cedex, France
        • Groupe Hospitaler Pellegrin, CHU De Bordeaux
      • Lille, France
        • CHRU de Lille - Hopital Albert Calmette
      • Marseille, France
        • CHU Marseille - Hopital Nord
      • Montpellier Cedex 5, France
        • CHU de Montpellier - Hôpital Arnaud de Villeneuve
      • Paris, France
        • Hopital Cochin
      • Paris Cedex 15, France
        • Hopital Necker, Enfants Malades
      • Rennes Cedex, France
        • Hopital PONTCHAILLOU CHU de Rennes
  • Germany
      • Berlin, Germany
        • Charite Paediatric Pulmonology Department
      • Erlangen, Germany
        • Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital
      • Essen, Germany
        • Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
      • Giessen, Germany
        • Justus-Liebig-Universitaet Gießen Zentrum fur Kinderheilkunde und Jugendmedizin
      • Halle, Germany
        • Universitätsklinikum Halle (Saale) / Universitätsklinik und Poliklinik für Innere Medizin, Schwerpunkt Pneumologie
      • Muenchen, Germany
        • Pneumologisches Studienzentrum Muenchen-West
      • Würzburg, Germany
        • University Hospital Wuerzburg
  • Ireland
      • Cork, Ireland
        • Cork University Hospital
      • Dublin, Ireland
        • Beaumont Hospital
      • Dublin, Ireland
        • St. Vincent's University Hospital
  • Israel
      • Limerick, Israel
        • University Hospital Limerick (Adults)
  • Italy
      • Ancona, Italy
        • Azienda Ospedaliero Universitaria Ospedale Riuniti
      • Genova, Italy
        • IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico
      • Milano, Italy
        • Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
      • Orbassano, Italy
        • Malattie Apparato Respiratorio 2 - Fibrosi Cistica
      • Rome, Italy
        • Ospedale Pediatrico Bambino Gesù
      • Verona, Italy
        • Azienda Ospedaliera di Verona-Ospedale Civile Maggiore
  • Netherlands
      • Den Haag, Netherlands
        • HagaZiekenhuis van Den Haag
      • Heidelberglaan, Netherlands
        • University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
      • Nijmegen, Netherlands
        • UMC St. Radboud
  • Spain
      • Barcelona, Spain
        • Hospital Universitari Vall d´Hebron Servicio de Broncoscopia
      • Murcia, Spain
        • Hospital Virgen de la Arrixaca
      • Sevilla, Spain
        • Hospital Universitario Virgen del Rocio
      • Valencia, Spain
        • Hospital Universitario y Politecnico La Fe
  • United Kingdom
      • Cambridge, United Kingdom
        • Papworth Hospital NHS Foundation Trust, Papworth Everard
      • Exeter, United Kingdom
        • Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
      • Glasgow, United Kingdom
        • Clinical Research Facility, Queen Elizabeth University Hospital
      • Leeds, United Kingdom
        • St. James University Hospital
      • 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
      • Southampton, United Kingdom
        • Southampton General Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham
    • Arizona
      • Tucson, Arizona, United States, 85724
        • Banner University of Arizona Medical Center
    • California
      • Long Beach, California, United States, 90806
        • Miller Children's Hospital / Long Beach Memorial
      • Palo Alto, California, United States, 94304
        • Stanford University
      • Sacramento, California, United States, 95817
        • University of California Davis Medical Center
      • San Francisco, California, United States, 94143
        • University of California San Francisco, Lung Transplant Program
    • Colorado
      • Denver, Colorado, United States, 80206
        • National Jewish Health
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine
      • Orlando, Florida, United States, 32803
        • Central Florida Pulmonary Group, PA
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • The University of Iowa Hospitals and Clinics
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cystic Fibrosis Center Clinical Rsearch Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-5212
        • Michigan Medicine
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine / St. Louis Children's Hospital
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center
    • New York
      • 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
      • New York, New York, United States, 10003
        • Mount Sinai Beth Israel
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • University of North Carolina Hospitals
    • Ohio
      • Cincinnati, Ohio, United States, 45220
        • UC Health Holmes
      • Cleveland, Ohio, United States, 44106
        • Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital
      • Toledo, Ohio, United States, 43606
        • ProMedica Toledo Hospital/Toledo Children's Hospital/Pediatric Pulmonary & Cystic Fibrosis Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • Texas
      • Austin, Texas, United States, 78723
        • Dell Children's Medical Group
      • Dallas, Texas, United States, 75390
        • The University of Texas Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • Texas Children's Hospital
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah / Primary Children's Medical Center
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Hospital and Clinics

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:

  • Subject has a confirmed diagnosis of CF and is heterozygous for F508del and either a gating or residual function mutation (F/G and F/RF genotypes)
  • 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: Control: IVA or TEZ/IVA
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 milligrams (mg) every 12 hours (q12h) or TEZ 100 mg once daily (qd)/IVA 150 mg q12h in the treatment period for 8 weeks.
Drug: TEZ/IVA
Fixed-dose combination (FDC) tablet for oral administration.
Other Names:
  • VX-661/VX-770
  • tezacaftor/ivacaftor
Drug: IVA
Mono-tablet for oral administration.
Other Names:
  • VX-770
  • ivacaftor
Experimental: TC: ELX/TEZ/IVA
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
Drug: ELX/TEZ/IVA
FDC tablet for oral administration.
Other Names:
  • VX-445/VX-661/VX-770
  • elexacaftor/tezacaftor/ivacaftor
Drug: IVA
Mono-tablet for oral administration.
Other Names:
  • VX-770
  • ivacaftor

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) for ELX/TEZ/IVA Group
Time Frame: From Baseline Through Week 8
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline Through Week 8

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Absolute Change in Sweat Chloride (SwCl) for ELX/TEZ/IVA Group
Time Frame: From Baseline Through Week 8
Sweat samples were collected using an approved collection device.
From Baseline Through Week 8
Absolute Change in ppFEV1 for the ELX/TEZ/IVA Group Compared to the Control Group
Time Frame: From Baseline Through Week 8
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline Through Week 8
Absolute Change in SwCl for ELX/TEZ/IVA Group Compared to the Control Group
Time Frame: From Baseline Through Week 8
Sweat samples were collected using an approved collection device.
From Baseline Through Week 8
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for ELX/TEZ/IVA Group
Time Frame: From Baseline Through Week 8
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 8
Absolute Change in CFQ-R Respiratory Domain Score for ELX/TEZ/IVA Group Compared to the Control Group
Time Frame: From Baseline Through Week 8
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 8
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: Day 1 up to Week 12
Day 1 up to Week 12

Collaborators and Investigators

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

Sponsor

Vertex Pharmaceuticals Incorporated

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

August 28, 2019

Primary Completion (Actual)

June 12, 2020

Study Completion (Actual)

June 12, 2020

Study Registration Dates

First Submitted

August 14, 2019

First Submitted That Met QC Criteria

August 14, 2019

First Posted (Actual)

August 15, 2019

Study Record Updates

Last Update Posted (Actual)

July 2, 2021

Last Update Submitted That Met QC Criteria

June 11, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VX18-445-104
  • 2018-002835-76 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent research/clinical-trial-data-sharing

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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