AzTrials
AzTrials

Cystic FibrosisPhase 3NCT04058353

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)

A Phase 3 study testing ELX/TEZ/IVA, IVA and TEZ/IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 93 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Cystic Fibrosis
What is being tested?
ELX/TEZ/IVA, IVA and TEZ/IVA
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
271 participants
Where
93 sitesin 13 countries
Study dates
28 Aug 2019to 12 Jun 2020
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

93 sites in 13 countries.

93 sites in 13 countries

United States37 sites

  • Michigan Medicine

    Ann Arbor, Michigan, 48109-5212

  • Dell Children's Medical Group

    Austin, Texas, 78723

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • Massachusetts General Hospital Cystic Fibrosis Center Clinical Rsearch Center

    Boston, Massachusetts, 02114

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

  • University of North Carolina Hospitals

    Chapel Hill, North Carolina, 27514

  • UC Health Holmes

    Cincinnati, Ohio, 45220

  • Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44106

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • The University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • National Jewish Health

    Denver, Colorado, 80206

  • Texas Children's Hospital

    Houston, Texas, 77030

  • Indiana University

    Indianapolis, Indiana, 46202

  • The University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • University of Kentucky

    Lexington, Kentucky, 40536

  • Miller Children's Hospital / Long Beach Memorial

    Long Beach, California, 90806

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • University of Miami Miller School of Medicine

    Miami, Florida, 33136

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Northwell Health- Long Island Jewish Medical Center

    New Hyde Park, New York, 11040

  • Mount Sinai Beth Israel

    New York, New York, 10003

  • Columbia University Medical Center

    New York, New York, 10032

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Central Florida Pulmonary Group, PA

    Orlando, Florida, 32803

  • Stanford University

    Palo Alto, California, 94304

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • University of California Davis Medical Center

    Sacramento, California, 95817

  • University of Utah / Primary Children's Medical Center

    Salt Lake City, Utah, 84132

  • University of California San Francisco, Lung Transplant Program

    San Francisco, California, 94143

  • University of Washington Medical Center

    Seattle, Washington, 98195

  • Washington University School of Medicine / St. Louis Children's Hospital

    St Louis, Missouri, 63110

  • ProMedica Toledo Hospital/Toledo Children's Hospital/Pediatric Pulmonary & Cystic Fibrosis Center

    Toledo, Ohio, 43606

  • Banner University of Arizona Medical Center

    Tucson, Arizona, 85724

Other trials in United States

France8 sites

  • Centre Hospitalier Lyon Sud

    Benite Cedex

  • Groupe Hospitaler Pellegrin, CHU De Bordeaux

    Bordeaux

  • CHRU de Lille - Hopital Albert Calmette

    Lille

  • CHU Marseille - Hopital Nord

    Marseille

  • CHU de Montpellier - Hopital Arnaud de Villeneuve

    Montpellier

  • Hopital Cochin

    Paris

  • Hopital Necker, Enfants Malades

    Paris

  • Hopital Pontchaillou CHU de Rennes

    Rennes

Other trials in France

United Kingdom8 sites

  • Papworth Hospital NHS Foundation Trust, Papworth Everard

    Cambridge

  • Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital

    Exeter

  • Clinical Research Facility, Queen Elizabeth University Hospital

    Glasgow

  • St. James University Hospital

    Leeds

  • Liverpool Heart and Chest Hospital

    Liverpool

  • Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital

    London

  • Wythenshawe Hospital

    Manchester

  • Southampton General Hospital

    Southampton

Other trials in United Kingdom

Australia7 sites

  • The Prince Charles Hospital

    Chermside

  • Alfred Hospital

    Melbourne, VIC

  • Perth Children's Hospital

    Nedlands

  • The Royal Children's Hospital

    Parkville, VIC

  • Mater Adult Hospital

    South Brisbane

  • Queensland Children's Hospital

    South Brisbane

  • Westmead Hospital

    Westmead

Other trials in Australia

Germany7 sites

  • Charite Paediatric Pulmonology Department

    Berlin

  • Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital

    Erlangen

  • Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen

    Essen

  • Justus-Liebig-Universitaet Gießen Zentrum fur Kinderheilkunde und Jugendmedizin

    Giessen

  • Universitätsklinikum Halle (Saale) / Universitätsklinik und Poliklinik für Innere Medizin, Schwerpunkt Pneumologie

    Halle

  • Pneumologisches Studienzentrum Muenchen-West

    München

  • University Hospital Wuerzburg

    Würzburg

Other trials in Germany

Italy6 sites

  • Azienda Ospedaliero Universitaria Ospedale Riuniti

    Ancona

  • IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico

    Genova

  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

    Milan

  • Malattie Apparato Respiratorio 2 - Fibrosi Cistica

    Orbassano

  • Ospedale Pediatrico Bambino Gesu

    Rome

  • Azienda Ospedaliera di Verona-Ospedale Civile Maggiore

    Verona

Other trials in Italy

Belgium4 sites

  • Cliniques Universitaires de Bruxelles Hopital Erasme

    Brussels

  • Universitair Ziekenhuis Brussel - Campus Jette

    Brussels

  • Universitair Ziekenhuis Gent

    Ghent

  • Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg

    Leuven

Other trials in Belgium

Canada4 sites

  • Stollery Children's Hospital

    Edmonton

  • McGill University Health Center

    Québec

  • St. Michael's Hospital

    Toronto

  • St. Paul's Hospital

    Vancouver

Other trials in Canada

Spain4 sites

  • Hospital Universitari Vall d´Hebron Servicio de Broncoscopia

    Barcelona

  • Hospital Virgen de la Arrixaca

    Murcia

  • Hospital Universitario Virgen del Rocio

    Seville

  • Hospital Universitario y Politecnico La Fe

    Valencia

Other trials in Spain

Ireland3 sites

  • Cork University Hospital

    Cork

  • Beaumont Hospital

    Dublin

  • St. Vincent's University Hospital

    Dublin

Other trials in Ireland

Netherlands3 sites

  • University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis

    Heidelberglaan

  • UMC St. Radboud

    Nijmegen

  • HagaZiekenhuis van den Haag

    The Hague

Other trials in Netherlands

Denmark1 site

  • Juliane Marie Center, Rigshospitalet

    Copenhagen

Other trials in Denmark

Israel1 site

  • University Hospital Limerick (Adults)

    Limerick

Other trials in Israel

About this study

Official title: 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).

Conditions
Cystic Fibrosis
Being tested
ELX/TEZ/IVA, IVA, TEZ/IVA
Medical subject headings
Cystic Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ELX/TEZ/IVADrug

    Also called VX-445/VX-661/VX-770, elexacaftor/tezacaftor/ivacaftor

    FDC tablet for oral administration.

  • IVADrug

    Also called VX-770, ivacaftor

    Mono-tablet for oral administration.

  • TEZ/IVADrug

    Also called VX-661/VX-770, tezacaftor/ivacaftor

    Fixed-dose combination (FDC) tablet for oral administration.

Study groups in NCT04058353
Study groupRoleWhat they receive
Control: IVA or TEZ/IVAActive comparatorFollowing 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.
Receives: Drug: IVA; Drug: TEZ/IVA
TC: ELX/TEZ/IVAExperimentalFollowing 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.
Receives: Drug: ELX/TEZ/IVA; Drug: IVA

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for ELX/TEZ/IVA Group

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

    Measured: From Baseline Through Week 8

Secondary outcomes (6)

  1. Absolute Change in Sweat Chloride (SwCl) for ELX/TEZ/IVA Group

    Sweat samples were collected using an approved collection device.

    Measured: From Baseline Through Week 8

  2. Absolute Change in ppFEV1 for the ELX/TEZ/IVA Group Compared to the Control Group

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

    Measured: From Baseline Through Week 8

  3. Absolute Change in SwCl for ELX/TEZ/IVA Group Compared to the Control Group

    Sweat samples were collected using an approved collection device.

    Measured: From Baseline Through Week 8

  4. Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for ELX/TEZ/IVA Group

    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.

    Measured: From Baseline Through Week 8

  5. Absolute Change in CFQ-R Respiratory Domain Score for ELX/TEZ/IVA Group Compared to the Control Group

    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.

    Measured: From Baseline Through Week 8

  6. Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    Measured: Day 1 up to Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Aug 2019
  2. Study start28 Aug 2019
  3. Primary completion12 Jun 2020
  4. Study completion12 Jun 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
271 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04058353
Sponsor's protocol ID
VX18-445-104
Other IDs
2018-002835-76, 2018
Status last verified
Jun 2021
First submitted
14 Aug 2019
Last updated
2 Jul 2021
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: 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
Expanded access
Available

Publications

  • Barry PJ, Mall MA, Alvarez A, Colombo C, de Winter-de Groot KM, Fajac I, McBennett KA, McKone EF, Ramsey BW, Sutharsan S, Taylor-Cousar JL, Tullis E, Ahluwalia N, Jun LS, Moskowitz SM, Prieto-Centurion V, Tian S, Waltz D, Xuan F, Zhang Y, Rowe SM, Polineni D; VX18-445-104 Study Group. Triple Therapy for Cystic Fibrosis Phe508del-Gating and -Residual Function Genotypes. N Engl J Med. 2021 Aug 26;385(9):815-825. doi: 10.1056/NEJMoa2100665.

    PubMed 34437784

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ELX/TEZ/IVA, IVA and TEZ/IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 93 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 93 sites in United States, France, United Kingdom, Australia, Germany and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for ELX/TEZ/IVA Group (time frame: From Baseline Through Week 8). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04058353, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in
Clinical Trial NCT04058353 | AzTrials