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Cystic FibrosisPhase 3NCT03525444

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)

A Phase 3 study testing VX-445/TEZ/IVA and IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 115 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 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). 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?
VX-445/TEZ/IVA and IVA
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
405 participants
Where
115 sitesin 13 countries
Study dates
15 Jun 2018to 24 Apr 2019
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

  • 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

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

115 sites in 13 countries.

115 sites in 13 countries

United States53 sites

  • Akron Children's Hospital

    Akron, Ohio, 44308

  • University of New Mexico Clinical & Translational Science Center

    Albuquerque, New Mexico, 87131

  • Children's Speciality Services at North Druid Hills

    Atlanta, Georgia, 30324

  • Augusta University

    Augusta, Georgia, 30912

  • Austin Children's Chest Associates

    Austin, Texas, 78723

  • Billings Clinic

    Billings, Montana, 59101

  • Massachusetts General Hospital Cystic Fibrosis Center

    Boston, Massachusetts, 02114

  • UNC Marsico Clinical Research Center

    Chapel Hill, North Carolina, 27517

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Virginia Primary Care Center

    Charlottesville, Virginia, 22908

  • Ann & Robert Lurie Children's Hospital of Chicago

    Chicago, Illinois, 60611

  • Northwestern Memorial Hospital

    Chicago, Illinois, 60611

  • UC Health Holmes

    Cincinnati, Ohio, 45220

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

    Cleveland, Ohio, 44106

  • Vermont Lung Center

    Colchester, Vermont, 05446

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • The University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

  • National Jewish Health

    Denver, Colorado, 80206

  • Harper University Hospital

    Detroit, Michigan, 48201

  • University of Florida, Shands Hospital

    Gainesville, Florida, 32610

  • Joe DiMaggio Cystic Fibrosis & Pulmonary Center/ Joe DiMaggio Children's Hospital/ Memorial Regional Hospital

    Hollywood, Florida, 33021

  • Nemours Children's Specialty Care

    Jacksonville, Florida, 32207

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Miller Children's Hospital/ Long Beach Memorial

    Long Beach, California, 90806

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Valley Children's Hospital/ Children's Hospital of Central California

    Madera, California, 93636

  • University of Wisconsin Hospitals and Clinics

    Madison, Wisconsin, 53792

  • CTSI Adult Translational Research Unit/Medical College of Wisconsin/Froedtert Hospital

    Milwaukee, Wisconsin, 53226

  • Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota

    Minneapolis, Minnesota, 55404

  • West Virginia University

    Morgantown, West Virginia, 26506

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • Tulane Medical Center

    New Orleans, Louisiana, 70112

  • Mount Sinai Beth Israel

    New York, New York, 10003

  • Children's Hospital of the King's Daughters

    Norfolk, Virginia, 23507

  • Kaiser Permanente

    Oakland, California, 94611

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Central Florida Pulmonary Group

    Orlando, Florida, 32803

  • Nemours Children's Hospital

    Orlando, Florida, 32827

  • Saint Francis Medical Center/ Children's Hospital of Illinois/OSF

    Peoria, Illinois, 61637

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Maine Medical Partners

    Portland, Maine, 04102

  • Children's Hospital of Richmond at VCU, Children's Pavilion

    Richmond, Virginia, 23298

  • University of California Davis Medical Center

    Sacramento, California, 95817

  • UCSF Gateway Medical Center

    San Francisco, California, 94143

  • University of Washington Medical Center

    Seattle, Washington, 98195

  • Tampa General Hospital Cardiac and Lung Transplant Clinic

    Tampa, Florida, 33606

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

    Toledo, Ohio, 43606

  • Banner University of Arizona Medical Center

    Tucson, Arizona, 85724

  • The University of Texas Health Science Center at Tyler

    Tyler, Texas, 75708

  • New York Medical College

    Valhalla, New York, 10595

Other trials in United States

United Kingdom9 sites

  • The Royal Belfast Hospital for Sick Children

    Belfast

  • Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital

    Brimingham

  • Royal Hospital for Sick Children

    Edinburgh

  • Western General Hospital

    Edinburgh

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

    Exeter

  • Leeds General Infirmary

    Leeds

  • King's College Hospital

    London

  • Royal Manchester Children's Hospital

    Manchester

  • Southampton General Hospital

    Southampton

Other trials in United Kingdom

Canada8 sites

  • University of Calgary Medical Clinic of the Foothills Medical Centre

    Calgary

  • McGill University Health Centre, Glen Site, Montreal Children's Hospital

    Montreal, Quebec

  • Centre Hospitalier De L'Universite Laval

    Qubec

  • Saint John Regional Hospital

    Saint John

  • The Hospital for Sick Children

    Toronto

  • British Columbia's Children's Hospital

    Vancouver, British Columbia

  • St. Paul's Hospital

    Vancouver, British Columbia

  • Vancouver Island Health Authority

    Victoria

Other trials in Canada

Germany8 sites

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

    Erlangen

  • Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin

    Giessen

  • Hannover Medical School

    Hanover

  • Heidelberg Cystic Fibrosis Center

    Heidelberg

  • Johannes Gutenberg-Universitaet

    Mainz

  • Dr. von Haunersches Kinderspital

    München

  • Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin

    Tübingen

  • University Hospital Wuerzburg

    Würzburg

Other trials in Germany

France7 sites

  • Centre Hospitalier Lyon Sud

    Benite Cedex

  • Groupe Hospitaler Pellegrin, CHU De Bordeaux

    Bordeaux

  • CHU Marseille - Hopital Nord

    Marseille

  • CHU de Nice - Hopital Pasteur

    Nice

  • Hopital Cochin

    Paris

  • CHU de Rouen - Hopital Charles Nicolle

    Rouen Cedex, Seine Maritime

  • Hopital Foch (Suresnes), Hopital Foch, Adultes

    Suresnes

Other trials in France

Italy7 sites

  • Azienda Ospedaliero Universitaria Ospedale Riuniti

    Ancona

  • Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer

    Florence

  • IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico

    Genova

  • Azienda Ospedaliera Universitaria Policlinico G. Martino

    Messina

  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

    Milan

  • Centro Regionale Fibrosi Cistica, A.O. Ospedale San Carlo

    Potenza

  • Azienda Ospedaliera di Verona-Ospedale Civile Maggiore

    Verona

Other trials in Italy

Australia5 sites

  • Women & Children's Hospital

    North Adelaide

  • The Royal Children's Hospital

    Parkville

  • Mater Adult Hospital

    South Brisbane

  • The Children's Hospital at Westmead

    Westmead

  • Westmead Hospital

    Westmead

Other trials in Australia

Belgium5 sites

  • Cliniques Universitaires de Bruxelles Hopital Erasme

    Brussels

  • Universitair Ziekenhuis Brussel - Campus Jette

    Brussels

  • UZ Antwerpen

    Edegem

  • Universitair Ziekenhuis Gent

    Ghent

  • Universitaire Ziekenhuizen Leuven - Campus Gathuisberg

    Leuven

Other trials in Belgium

Netherlands5 sites

  • Academic Medical Center

    Amsterdam

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

    Heidelberglaan

  • UMC St. Radboud

    Nijmegen

  • Erasmus Medical Center

    Rotterdam

  • HagaZiekenhuis van den Haag

    The Hague

Other trials in Netherlands

Austria4 sites

  • University of Graz

    Graz

  • Medizinische Universitat Innsbruck

    Innsbruck

  • LKH - Universitätsklinikum der PMU Salzburg

    Salzburg

  • Medizinische Universitat Wien

    Vienna

Other trials in Austria

Czechia2 sites

  • Fakultni Nemocnice Brno

    Brno

  • Fakultni nemocnice v Motole

    Prague

Other trials in Czechia

Greece1 site

  • General Hospital of Attika "Sismanoglio"(Adult CF center, NHS)

    Marousi

Other trials in Greece

Sweden1 site

  • Karolinska Univeritetssjukhuset, Huddinge

    Stockholm

Other trials in Sweden

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 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).

Conditions
Cystic Fibrosis
Being tested
VX-445/TEZ/IVA, IVA, Placebo
Medical subject headings
Cystic Fibrosis

What participants receive

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

  • VX-445/TEZ/IVADrug

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

    Participants received VX-445/TEZ/IVA orally once daily in the morning.

  • IVADrug

    Also called VX-770, ivacaftor

    Participants received IVA orally once daily in the evening

  • PlaceboDrug

    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.

Study groups in NCT03525444
Study groupRoleWhat they receive
PlaceboPlacebo comparatorParticipants who received placebo matched to VX-445/TEZ/IVA for 24 weeks in the TC treatment period.
Receives: Drug: Placebo
VX-445/TEZ/IVA TCExperimentalParticipants 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.
Receives: Drug: VX-445/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)

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

    Measured: From Baseline at Week 4

Secondary outcomes (12)

  1. Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

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

    Measured: From Baseline through Week 24

  2. Number of Pulmonary Exacerbations (PEx)

    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.

    Measured: From Baseline through Week 24

  3. Absolute Change in Sweat Chloride (SwCl)

    Sweat samples were collected using an approved collection device.

    Measured: From Baseline through Week 24

  4. Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score

    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 24

  5. Absolute Change in Body Mass Index (BMI)

    BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).

    Measured: From Baseline at Week 24

  6. Absolute Change in Sweat Chloride

    Sweat samples were collected using an approved collection device.

    Measured: From Baseline at Week 4

  7. Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score

    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 at Week 4

  8. Time-to-first Pulmonary Exacerbation (PEx)

    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.

    Measured: From Baseline through Week 24

  9. Absolute Change in BMI Z-score for Participants <=20 Years of Age at Baseline

    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.

    Measured: From Baseline at Week 24

  10. Absolute Change in Body Weight

    Measured: From Baseline at Week 24

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

    Measured: 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)

  12. Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ, M1-TEZ, and IVA

    Measured: Pre-dose on Week 4, 8, 12, and 16

Timeline

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

  1. First posted15 May 2018
  2. Study start15 Jun 2018
  3. Primary completion24 Apr 2019
  4. Study completion24 Apr 2019

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
405 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03525444
Sponsor's protocol ID
VX17-445-102
Other IDs
2018-000183-28, 2018
Status last verified
May 2020
First submitted
2 May 2018
Last updated
19 May 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.

    PubMed 37983082

  • Middleton PG, Mall MA, Drevinek P, Lands LC, McKone EF, Polineni D, Ramsey BW, Taylor-Cousar JL, Tullis E, Vermeulen F, Marigowda G, McKee CM, Moskowitz SM, Nair N, Savage J, Simard C, Tian S, Waltz D, Xuan F, Rowe SM, Jain R; VX17-445-102 Study Group. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019 Nov 7;381(19):1809-1819. doi: 10.1056/NEJMoa1908639. Epub 2019 Oct 31.

    PubMed 31697873

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing VX-445/TEZ/IVA and IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 115 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 19 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 115 sites in United States, United Kingdom, Canada, Germany, France 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. Some participants in this study may receive a placebo. 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 19 May 2020). 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) (time frame: From Baseline at Week 4). 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 NCT03525444, which also lists 2 linked publications.

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 19 May 2020.

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