A Study to Evaluate the Safety and Efficacy of Long-term Treatment With TEZ/IVA in CF Participants With an F508del CFTR Mutation

March 28, 2024 updated by: Vertex Pharmaceuticals Incorporated

A Phase 3, Open-label, Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Tezacaftor in Combination With Ivacaftor in Subjects With Cystic Fibrosis Aged 6 Years and Older, Homozygous or Heterozygous for the F508del-CFTR Mutation

This study evaluates the long-term safety and tolerability of tezacaftor in combination with ivacaftor (TEZ/IVA) in participants with cystic fibrosis (CF) aged 6 years and older, homozygous or heterozygous for the F508del mutation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

130

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
      • Nedlands, Australia
        • Perth Children's Hospital
      • New Lambton, Australia
        • John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital
      • South Brisbane, Australia
        • Lady Cilento Children's Hospital
      • Westmead, Australia
        • The Children's Hospital at Westmead
  • Belgium
      • Brussels, Belgium
        • Universitair Ziekenhuis Brussel - Campus Jette
      • Leuven, Belgium
        • Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
        • British Columbia's Children's Hospital
    • Ontario
      • Toronto, Ontario, Canada
        • The Hospital for Sick Children
    • Quebec
      • Montreal, Quebec, Canada
        • McGill University Health Centre, Glen Site, Montreal Children's Hospital
  • Denmark
      • Copenhagen, Denmark
        • Juliane Marie Center, Rigshopitalet
  • France
      • Bordeaux cedex, France
        • Groupe Hospitaler Pellegrin, CHU De Bordeaux
      • Paris Cedex 15, France
        • Hopital Necker, Enfants Malades
  • Germany
      • Essen, Germany
        • Universitätsklinikum Essen
      • Frankfurt, Germany
        • Clinic of J.W. Goethe University
      • Giessen, Germany
        • Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin
      • Hannover, Germany
        • Medizinische Hochschule Hannover
      • Jena, Germany
        • Universitaetsklinikum Jena, Mukoviszidose-Zentrum
      • Koeln, Germany
        • Universitaetsklinkum Koeln, CF-Studienzentrum
      • Tuebingen, Germany
        • Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin
  • Ireland
      • Dublin, Ireland
        • Our Lady's Children's Hospital
      • Limerick, Ireland
        • University Hospital Limerick
  • Poland
      • Lomianki, Poland
        • Klinika Mukowiscydozy IMD Oddozial Chorob Pluc Szpzoz IM. Dzieci WarszaWY
  • Switzerland
      • Bern, Switzerland
        • Inselspital - Universitaetsspital Bern
      • Zürich, Switzerland
        • Kinderspital Zuerich
  • United Kingdom
      • Leeds, United Kingdom
        • Leeds General Infirmary
      • London, United Kingdom
        • Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
      • Southampton, United Kingdom
        • Southampton General Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham
    • Alaska
      • Anchorage, Alaska, United States, 99508
        • Providence Alaska Medical Center
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Arkansas Children's Hospital
    • California
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Nemours/ Alfred I. duPont Hospital for Children
    • Florida
      • Saint Petersburg, Florida, United States, 33701
        • Johns Hopkins All Children's Hospital Outpatient Care Center
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Center for Advanced Pediatrics
    • Idaho
      • Boise, Idaho, United States, 83702
        • St. Luke's CF Center of Idaho
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children Indiana University Health
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Children's Hospital & Clinics of Minnesota
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • The Children's Mercy Hospital
    • New Hampshire
      • Manchester, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center
    • New York
      • Buffalo, New York, United States, 14203
        • UBMD Pediatrics/ CF Center of Western New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • Syracuse, New York, United States, 13202
        • Suny Upstate Medical University
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest Baptist Health
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina (MUSC)
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57105
        • Sanford Children's Speciality Clinic
    • Texas
      • Austin, Texas, United States, 78723
        • Austin Children's Chest Associates
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
    • Virginia
      • Norfolk, Virginia, United States, 23507
        • Children's Hospital of The King's Daughters
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Children's Hospital of Wisconsin

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

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

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Completed the Week 24 Visit in Study 113 Part B or the Week 8 Visit in Study 115
  • Eligible CFTR Mutation

Exclusion Criteria:

  • Pregnant and nursing females
  • History of poor compliance with study drug and/or procedures in a previous study as deemed by the investigator
  • Ongoing participation in another study with investigational drug

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TEZ/IVA

Part A: Participants weighing less than (<)40 kilograms (kg) at Day 1 received tezacaftor (TEZ) 50 milligrams (mg) once daily (qd)/ivacaftor (IVA) 75 mg every 12 hours (q12h) and the participants weighing greater than or equals to (>=) 40 kg at Day 1 received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 96 weeks. Doses were adjusted upward for changes in body weight and/or age.

Part B: Participants weighing <30 kg at Day 1 received TEZ 50 mg qd/IVA 75 mg q12h and the participants weighing >=30 kg at Day 1 received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period up to 192 weeks. Doses were adjusted upward for changes in body weight and/or age.
Drug: IVA
Tablet for oral administration.
Other Names:
  • VX-770
  • ivacaftor
Drug: TEZ/IVA
Fixed-dose combination tablet for oral administration.
Other Names:
  • VX-661/VX-770
  • tezacaftor/ivacaftor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Part A: 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 100
Day 1 up to Week 100

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: Absolute Change in SwCl for 113B/116 FAS
Time Frame: From Parent Study 113B Baseline at Week 96 (Study 116)
Sweat samples were collected using an approved collection device.
From Parent Study 113B Baseline at Week 96 (Study 116)
Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 115/116 FAS (TEZ/IVA Group)
Time Frame: From Parent Study 115 Baseline at Week 96 (Study 116)
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
From Parent Study 115 Baseline at Week 96 (Study 116)
Part A: Absolute Change in CFQ-R Respiratory Domain Score for 113B/116 FAS
Time Frame: From Parent Study 113B Baseline at Week 96 (Study 116)
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
From Parent Study 113B Baseline at Week 96 (Study 116)
Part A: Absolute Change in Body Mass Index (BMI) for 115/116 FAS (TEZ/IVA Group)
Time Frame: From Parent Study 115 Baseline at Week 96 (Study 116)
BMI was defined as weight in kilograms (kg) divided by squared height in meters (m^2).
From Parent Study 115 Baseline at Week 96 (Study 116)
Part A: Absolute Change in BMI for 113B/116 FAS
Time Frame: From Parent Study 113B Baseline at Week 96 (Study 116)
BMI was defined as weight in kg divided by m^2.
From Parent Study 113B Baseline at Week 96 (Study 116)
Part A: Absolute Change in Lung Clearance Index2.5 (LCI2.5) for 115/116 FAS (TEZ/IVA Group)
Time Frame: From Parent Study 115 Baseline at Week 96 (Study 116)
The LCI2.5 index is the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting values and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured functional residual capacity (FRC). An LCI of 7.5 and below is normal; values greater than 7.5 are abnormal. LCI is able to detect abnormalities in lung function earlier than more traditional modalities such as spirometry.
From Parent Study 115 Baseline at Week 96 (Study 116)
Part A: Absolute Change in LCI2.5 for 113B/116 LCI FAS
Time Frame: From Parent Study 113B Baseline at Week 96 (Study 116)
The LCI2.5 index is the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting values and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured functional residual capacity (FRC). An LCI of 7.5 and below is normal; values greater than 7.5 are abnormal. LCI is able to detect abnormalities in lung function earlier than more traditional modalities such as spirometry.
From Parent Study 113B Baseline at Week 96 (Study 116)
Part A: Absolute Change in Sweat Chloride (SwCl) for 115/116 FAS (TEZ/IVA Group)
Time Frame: From Parent Study 115 Baseline at Week 96 (Study 116)
Sweat samples were collected using an approved collection device.
From Parent Study 115 Baseline at Week 96 (Study 116)
Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Day 1 up to Week 192
Day 1 up to Week 192

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)

April 25, 2018

Primary Completion (Actual)

October 28, 2020

Study Completion (Actual)

September 29, 2023

Study Registration Dates

First Submitted

May 15, 2018

First Submitted That Met QC Criteria

May 24, 2018

First Posted (Actual)

May 25, 2018

Study Record Updates

Last Update Posted (Actual)

April 19, 2024

Last Update Submitted That Met QC Criteria

March 28, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VX17-661-116
  • 2017-002968-40 (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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