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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
271

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Expanded Access

Expanded Access

A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved by the U.S. Food and Drug Administration (FDA). Also called compassionate use. There are different expanded access types.
Approved

Approved

  • Available: Expanded access is currently available for this investigational treatment, and patients who are not participants in the clinical study may be able to gain access to the drug, biologic, or medical device being studied.
  • No longer available: Expanded access was available for this intervention previously but is not currently available and will not be available in the future.
  • Temporarily not available: Expanded access is not currently available for this intervention but is expected to be available in the future.
  • Approved for marketing: The intervention has been approved by the U.S. Food and Drug Administration for use by the public.
 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 - Hôpital 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 Gesu
      • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 28, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 12, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 12, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 14, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 14, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 15, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 2, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 11, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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