A Study of VX-445 Combination Therapy in CF Subjects Homozygous for F508del (F/F)

January 24, 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 Homozygous for the F508del Mutation (F/F)

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 homozygous for the F508del mutation (F/F)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

113

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

  • 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 Gasthuisberg
  • 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
  • United Kingdom
      • Belfast, United Kingdom
        • The Royal Belfast Hospital for Sick Children
      • Birmingham, United Kingdom
        • Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
      • 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
      • 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
    • Colorado
      • Denver, Colorado, United States, 80206
        • National Jewish Health
    • Florida
      • Hollywood, Florida, United States, 33021
        • Joe DiMaggio Cystic Fibrosis & Pulmonary Center/ Joe DiMaggio Children's Hospital/ Memorial Regional Hospital
      • Orlando, Florida, United States, 32827
        • Nemours Children's Hospital
      • Orlando, Florida, United States, 32803
        • Central Florida Pulmonary Group, PA
      • Tampa, Florida, United States, 33606
        • Tampa General Hospital Cardiac and Lung Transplant Clinic
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital
      • Peoria, Illinois, United States, 61637
        • Saint Francis Medical Center/ Children's Hospital of Illinoise/OSF
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cystic Fibrosis Center Clinical Research Center
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Harper University Hospital
    • New York
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27517
        • UNC Marisco Clinical Research Center
    • Ohio
      • 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
      • 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
      • Dallas, Texas, United States, 75390
        • The University of Texas Southwestern Medical Center
    • Vermont
      • Colchester, Vermont, United States, 05446
        • Vermont Lung Center
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Primary Care Center
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • West Virginia University

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 (ADULT, OLDER_ADULT, CHILD)

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
  • 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 to VX-445/TEZ/IVA orally once daily in the morning.
Drug: Placebo
Participants received placebo matched TEZ/IVA orally once daily in the morning.
EXPERIMENTAL: VX-445/TEZ/IVA TC
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 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: IVA
Participants received IVA orally once daily in the evening.
Other Names:
  • VX-770
  • ivacaftor
Drug: Placebo
Participants received placebo matched to VX-445/TEZ/IVA orally once daily in the morning.
Drug: Placebo
Participants received placebo matched TEZ/IVA orally once daily in the morning.
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

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 indicate fewer symptoms and better health-related quality of life.
From Baseline at Week 4
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 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-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA
Time Frame: Day 1 and Week 4
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

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 3, 2018

Primary Completion (ACTUAL)

December 28, 2018

Study Completion (ACTUAL)

December 28, 2018

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)

January 27, 2020

Last Update Submitted That Met QC Criteria

January 24, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VX17-445-103
  • 2018-000184-89 (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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