A Phase 3 Study of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)

May 6, 2020 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 Minimal Function Mutation (F/MF)

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 heterozygous for F508del and a minimal function mutation (F/MF subjects).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

405

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
      • North Adelaide, Australia
        • Women & Children's Hospital
      • Parkville, Australia
        • The Royal Children's Hospital
      • South Brisbane, Australia
        • Mater Adult Hospital
      • Westmead, Australia
        • The Children's Hospital at Westmead
      • Westmead, Australia
        • Westmead Hospital
  • Austria
      • Graz, Austria
        • University of Graz
      • Innsbruck, Austria
        • Medizinische Universität Innsbruck
      • Salzburg, Austria
        • Lkh - Universitatsklinikum Der Pmu Salzburg
      • Vienna, Austria
        • Medizinische Universität Wien
  • Belgium
      • Brussels, Belgium
        • Universitair Ziekenhuis Brussel - Campus Jette
      • Brussels, Belgium
        • Cliniques Universitaires de Bruxelles Hopital Erasme
      • Edegem, Belgium
        • UZ Antwerpen
      • Gent, Belgium
        • Universitair Ziekenhuis Gent
      • Leuven, Belgium
        • Universitaire Ziekenhuizen Leuven - Campus Gathuisberg
  • Canada
      • Calgary, Canada
        • University of Calgary Medical Clinic of the Foothills Medical Centre
      • Qubec, Canada
        • Centre Hospitalier de l'Université Laval
      • Saint John, Canada
        • Saint John Regional Hospital
      • Toronto, Canada
        • The Hospital for Sick Children
      • Victoria, Canada
        • Vancouver Island Health Authority
    • British Columbia
      • Vancouver, British Columbia, Canada
        • St. Paul's Hospital
      • Vancouver, British Columbia, Canada
        • British Columbia's Children's Hospital
    • Quebec
      • Montréal, Quebec, Canada
        • McGill University Health Centre, Glen Site, Montreal Children's Hospital
  • Czechia
      • Brno, Czechia
        • Fakultni nemocnice Brno
      • Praha 5, Czechia
        • Fakultni nemocnice v Motole
  • France
      • Benite Cedex, France
        • Centre Hospitalier LYON SUD
      • Bordeaux Cedex, France
        • Groupe Hospitaler Pellegrin, CHU De Bordeaux
      • Marseille, France
        • Chu Marseille - Hopital Nord
      • Nice, France
        • CHU de Nice - Hopital Pasteur
      • Paris, France
        • Hôpital Cochin
      • Rouen Cedex, Seine Maritime, France
        • CHU de Rouen - Hôpital Charles Nicolle
      • Suresnes, France
        • Hopital Foch (Suresnes), Hopital Foch, Adultes
  • Germany
      • Erlangen, Germany
        • Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital
      • Giessen, Germany
        • Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin
      • Hannover, Germany
        • Hannover Medical School
      • Heidelberg, Germany
        • Heidelberg Cystic Fibrosis Center
      • Mainz, Germany
        • Johannes Gutenberg-Universitaet
      • München, Germany
        • Dr. von Haunersches Kinderspital
      • Tuebingen, Germany
        • Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin
      • Wuerzburg, Germany
        • University Hospital Wuerzburg
  • Greece
      • Maroúsi, Greece
        • General Hospital of Attika "Sismanoglio"(Adult CF center, NHS)
  • Italy
      • Ancona, Italy
        • Azienda Ospedaliero Universitaria Ospedale Riuniti
      • Firenze, Italy
        • Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer
      • Genova, Italy
        • IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico
      • Messina, Italy
        • Azienda Ospedaliera Universitaria Policlinico G. Martino
      • Milano, Italy
        • Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
      • Potenza, Italy
        • Centro Regionale Fibrosi Cistica, A.O. Ospedale San Carlo
      • Verona, Italy
        • Azienda Ospedaliera di Verona-Ospedale Civile Maggiore
  • Netherlands
      • Amsterdam, Netherlands
        • Academic Medical Center
      • Den Haag, Netherlands
        • HagaZiekenhuis van den Haag
      • Heidelberglaan, Netherlands
        • University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
      • Nijmegen, Netherlands
        • UMC St. Radboud
      • Rotterdam, Netherlands
        • Erasmus Medical Center
  • Sweden
      • Stockholm, Sweden
        • Karolinska Univeritetssjukhuset, Huddinge
  • United Kingdom
      • Belfast, United Kingdom
        • The Royal Belfast Hospital for Sick Children
      • Brimingham, United Kingdom
        • Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
      • Edinburgh, United Kingdom
        • Western General Hospital
      • Edinburgh, United Kingdom
        • Royal Hospital for Sick Children
      • Exeter, United Kingdom
        • Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
      • Leeds, United Kingdom
        • Leeds General Infirmary
      • London, United Kingdom
        • King's College Hospital
      • Manchester, United Kingdom
        • Royal Manchester Children's Hospital
      • Southampton, United Kingdom
        • Southampton General Hospital
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724
        • Banner University of Arizona Medical Center
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
    • California
      • Long Beach, California, United States, 90806
        • Miller Children's Hospital/ Long Beach Memorial
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
      • Madera, California, United States, 93636
        • Valley Children's Hospital/ Children's Hospital of Central California
      • Oakland, California, United States, 94611
        • Kaiser Permanente
      • Sacramento, California, United States, 95817
        • University of California Davis Medical Center
      • San Francisco, California, United States, 94143
        • UCSF Gateway Medical Center
    • Colorado
      • Denver, Colorado, United States, 80206
        • National Jewish Health
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida, Shands Hospital
      • Hollywood, Florida, United States, 33021
        • Joe DiMaggio Cystic Fibrosis & Pulmonary Center/ Joe DiMaggio Children's Hospital/ Memorial Regional Hospital
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Specialty Care
      • Orlando, Florida, United States, 32803
        • Central Florida Pulmonary Group
      • Orlando, Florida, United States, 32827
        • Nemours Children's Hospital
      • Tampa, Florida, United States, 33606
        • Tampa General Hospital Cardiac and Lung Transplant Clinic
    • Georgia
      • Atlanta, Georgia, United States, 30324
        • Children's Speciality Services at North Druid Hills
      • Augusta, Georgia, United States, 30912
        • Augusta University
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital
      • Chicago, Illinois, United States, 60611
        • Ann & Robert Lurie Children's Hospital of Chicago
      • Peoria, Illinois, United States, 61637
        • Saint Francis Medical Center/ Children's Hospital of Illinois/OSF
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane Medical Center
    • Maine
      • Portland, Maine, United States, 04102
        • Maine Medical Partners
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cystic Fibrosis Center
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Harper University Hospital
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota
    • Montana
      • Billings, Montana, United States, 59101
        • Billings Clinic
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Nebraska Medical Center
    • New Jersey
      • Morristown, New Jersey, United States, 07960
        • Morristown Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • University of New Mexico Clinical & Translational Science Center
    • New York
      • New York, New York, United States, 10003
        • Mount Sinai Beth Israel
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27517
        • UNC Marsico Clinical Research Center
    • Ohio
      • Akron, Ohio, United States, 44308
        • Akron Children's Hospital
      • Cincinnati, Ohio, United States, 45220
        • UC Health Holmes
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Cleveland Medical Center/ Rainbow Babies and Children's Hospital
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital
      • Dayton, Ohio, United States, 45404
        • Dayton 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
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Texas
      • Austin, Texas, United States, 78723
        • Austin Children's Chest Associates
      • Dallas, Texas, United States, 75390
        • The University of Texas Southwestern Medical Center
      • Tyler, Texas, United States, 75708
        • The University of Texas Health Science Center at Tyler
    • Vermont
      • Colchester, Vermont, United States, 05446
        • Vermont Lung Center
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Primary Care Center
      • Norfolk, Virginia, United States, 23507
        • Children's Hospital of The King's Daughters
      • Richmond, Virginia, United States, 23298
        • Children's Hospital of Richmond at VCU, Children's Pavilion
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • West Virginia University
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Hospitals and Clinics
      • Milwaukee, Wisconsin, United States, 53226
        • CTSI Adult Translational Research Unit/Medical College of Wisconsin/Froedtert 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:

  • Heterozygous for the F508del mutation (F/MF)
  • 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
Placebo Comparator: Placebo
Participants who received placebo matched to VX-445/TEZ/IVA for 24 weeks in the TC treatment period.
Drug: Placebo
Participants received placebo matched VX-445/TEZ/IVA orally once daily in the morning and placebo matched to IVA orally once daily in the evening.
Experimental: VX-445/TEZ/IVA TC
Participants who received VX-445 200 mg/TEZ 100 mg/IVA150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 weeks in the TC treatment period.
Drug: VX-445/TEZ/IVA
Participants received VX-445/TEZ/IVA orally once daily in the morning.
Other Names:
  • VX-445/VX-661/VX-770
  • VX-445/tezacaftor/ivacaftor
Drug: IVA
Participants received IVA orally once daily in the evening
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)
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 Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Time Frame: From Baseline through Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline through Week 24
Number of Pulmonary Exacerbations (PEx)
Time Frame: From Baseline through Week 24
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
Absolute Change in Sweat Chloride (SwCl)
Time Frame: From Baseline through Week 24
Sweat samples were collected using an approved collection device.
From Baseline through Week 24
Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score
Time Frame: From Baseline through Week 24
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
Absolute Change in Body Mass Index (BMI)
Time Frame: From Baseline at Week 24
BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).
From Baseline at Week 24
Absolute Change in Sweat Chloride
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
Time-to-first Pulmonary Exacerbation (PEx)
Time Frame: From Baseline through Week 24
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
Absolute Change in Body Weight
Time Frame: From Baseline at Week 24
From Baseline at Week 24
Safety and Tolerability as Assessed by 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 28 weeks)
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)
Absolute Change in BMI Z-score for Participants <=20 Years of Age at Baseline
Time Frame: From Baseline at Week 24
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
Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ, M1-TEZ, and IVA
Time Frame: Pre-dose on Week 4, 8, 12, and 16
Pre-dose on Week 4, 8, 12, and 16

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)

June 15, 2018

Primary Completion (Actual)

April 24, 2019

Study Completion (Actual)

April 24, 2019

Study Registration Dates

First Submitted

May 2, 2018

First Submitted That Met QC Criteria

May 2, 2018

First Posted (Actual)

May 15, 2018

Study Record Updates

Last Update Posted (Actual)

May 19, 2020

Last Update Submitted That Met QC Criteria

May 6, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VX17-445-102
  • 2018-000183-28 (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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