AzTrials
AzTrials

Cystic FibrosisPhase 3NCT05033080

A Phase 3 Study of VX-121 Combination Therapy in Participants With Cystic Fibrosis (CF) Heterozygous for F508del and a Minimal Function Mutation (F/MF)

A Phase 3 study testing VX-121/TEZ/D-IVA, ELX/TEZ/IVA and IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 139 sites in 12 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

The purpose of this study evaluates the efficacy and safety of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF participants who were heterozygous for F508del and a minimal function mutation (F/MF participants). 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-121/TEZ/D-IVA, ELX/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
435 participants
Where
139 sitesin 12 countries
Study dates
14 Sep 2021to 21 Nov 2023
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 F508del and a minimal function mutation (F/MF genotype)
  • Forced expiratory volume in 1 second (FEV1) value >=40% and <=90% of predicted mean for age, sex, and height for participants currently receiving ELX/TEZ/IVA therapy; FEV1 >=40% and <=80% for participants not currently receiving ELX/TEZ/IVA

Who cannot join

  • History of solid organ or hematological transplantation
  • Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
  • Lung infection with organisms associated with a more rapid decline in pulmonary status
  • Pregnant or breast-feeding females
  • Other protocol defined Inclusion/Exclusion criteria may apply

Trial locations and contacts

139 sites in 12 countries.

139 sites in 12 countries

United States69 sites

  • Albany Medical College

    Albany, New York, 12208

  • Michigan Medicine

    Ann Arbor, Michigan, 48109-5212

  • The Emory Clinic at Chantilly

    Atlanta, Georgia, 30324

  • Augusta University

    Augusta, Georgia, 30912

  • Children's Hospital of Colorado

    Aurora, Colorado, 80045

  • Billings Clinic

    Billings, Montana, 59101

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • St. Luke's Cystic Fibrosis Center of Idaho

    Boise, Idaho, 83702

  • Massachusetts General Hospital Cystic Fibrosis Center Clinical Rsearch Center

    Boston, Massachusetts, 02114

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

  • CF Therapeutics Development Center of Western New York

    Buffalo, New York, 14203

  • Atrium Health Levine Children's Hospital

    Charlotte, North Carolina, 28203

  • University of Virginia Health System

    Charlottesville, Virginia, 22908

  • Ann & Robert H. Lurie Children's Hospital of Chicago

    Chicago, Illinois, 60611

  • Northwestern Memorial Hospital

    Chicago, Illinois, 60611

  • Cleveland Clinic CF

    Cleveland, Ohio, 44195

  • Vermont Lung Center

    Colchester, Vermont, 05446

  • Childrens Hospital University of Missouri Health Sciences Center

    Columbia, Missouri, 65212

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Driscoll Children's Hospital

    Corpus Christi, Texas, 78411

  • The University of Texas Southwestern Medical Center

    Dallas, Texas, 75390-8558

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

  • National Jewish Health

    Denver, Colorado, 80206

  • Inova Fairfax

    Falls Church, Virginia, 22042

  • Cook Children's Health Care System

    Fort Worth, Texas, 76104

  • University of Florida, Shands Hospital

    Gainesville, Florida, 32610

  • Helen DeVos Children's Hospital CF Center

    Grand Rapids, Michigan, 49503

  • Joe DiMaggio Cystic Fibrosis & Pulmonary Center

    Hollywood, Florida, 33021

  • Texas Children's Hospital - Baylor College of Medicine

    Houston, Texas, 77030

  • Indiana University

    Indianapolis, Indiana, 46202

  • Riley Hospital for Children at Indiana University Health

    Indianapolis, Indiana, 46202

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • The Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • University of Tennessee Medical Center

    Knoxville, Tennessee, 37920

  • University of Kentucky

    Lexington, Kentucky, 40536

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202

  • Miller Children's Hospital / Long Beach Memorial

    Long Beach, California, 90806

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Kosair Charities Pediatric Clinical Research Unit

    Louisville, Kentucky, 40202

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Dartmouth Hitchcock, Manchester

    Manchester, New Hampshire, 03104

  • Children's Foundation Research Center / Le Bonheur Children's Hospital

    Memphis, Tennessee, 38105

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Northwell Health- Long Island Jewish Medical Center

    New Hyde Park, New York, 11040

  • Tulane Medical Center

    New Orleans, Louisiana, 70112

  • Columbia University Medical Center

    New York, New York, 10032

  • Kaiser Permanente

    Oakland, California, 94611

  • Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Central Florida Pulmonary Group, PA

    Orlando, Florida, 32803

  • Nemours Children's Hospital

    Orlando, Florida, 32827

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • UPMC Children's Hospital of Pittsburgh

    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

  • Sanford Children's Speciality Clinic

    Sioux Falls, South Dakota, 57105

  • Cardinal Glennon Children's Hospital - St. Louis University

    St Louis, Missouri, 63104

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

    St Louis, Missouri, 63110

  • Johns Hopkins All Children's Hospital Outpatient Care Center

    St. Petersburg, Florida, 33701

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

    Toledo, Ohio, 43606

  • Banner University of Arizona Medical Center

    Tucson, Arizona, 85724

  • New York Medical College

    Valhalla, New York, 10595

  • Wake Forest Baptist Health

    Winston-Salem, North Carolina, 27104

  • UMass Memorial Medical Center

    Worcester, Massachusetts, 01655

Other trials in United States

United Kingdom16 sites

  • Birmingham Heartlands Hospital

    Birmingham

  • University Hospitals Bristol and Weston NHS Foundation Trust, Bristol Royal Hospital

    Bristol

  • Royal Papworth Hospital NHS Foundation Trust

    Cambridge

  • Royal Hospital for Sick Children

    Edinburgh

  • Western General Hospital

    Edinburgh

  • 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

  • King's College Hospital

    London

  • Royal Brompton Hospital

    London

  • St. Bartholomew's Hospital

    London

  • Wythenshawe Hospital

    Manchester

  • Clinical Research Facility

    Newcastle upon Tyne

  • All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough

    Penarth

  • Southampton General Hospital

    Southampton

Other trials in United Kingdom

Germany15 sites

  • Charite Paediatric Pulmonology Department

    Berlin

  • St. Josef-Hospital

    Bochum

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

    Erlangen

  • Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen

    Essen

  • Universitatsklinikum Essen (AoR), Kinderklinik III, Abt. fur Pneumologie

    Essen

  • Johann Wolfgang Goethe University

    Frankfurt

  • Hannover Medical School

    Hanover

  • Medizinische Hochschule Hannover

    Hanover

  • Mukoviszidose-Zentrum am Universitätsklinikum Jena, Klinik für Kinder- und Jugendmedizin

    Jena

  • Johannes Gutenberg-Universitaet

    Mainz

  • Klinikum Innenstadt, University of Munich

    München

  • Pneumologisches Studienzentrum Muenchen-West

    München

  • Klinikum Westbrandenburg (CF)

    Potsdam

  • Universitätsklinikum Ulm, Klinik für Kinder- und Jugendmedizin (CF)

    Ulm

  • Universitätsklinikum Würzburg

    Würzburg

Other trials in Germany

Spain9 sites

  • Hospital Saint Joan de Deu

    Barcelona

  • Hospital Universitari Vall d Hebron

    Barcelona

  • Hospital Infantil Universitario Nino Jesus

    Madrid

  • Hospital Universitario 12 de Octubre

    Madrid

  • Hospital Universitario Ramon y Cajal

    Madrid

  • Hospital Virgen de la Arrixaca

    Murcia

  • Corporacio Sanitaria Parc Tauli - Sabadell Hospital Universitari

    Sabadell

  • Hospital Universitario Virgen del Rocio

    Seville

  • Hospital Universitario y Politecnico La Fe

    Valencia

Other trials in Spain

Ireland7 sites

  • Cork University Hospital

    Cork

  • Children's Health Ireland at Crumlin

    Dublin

  • Children's Health Ireland at Tallaght

    Dublin

  • Children's Health Ireland at Temple Street

    Dublin

  • St. Vincent's University Hospital

    Dublin

  • University Hospital Limerick (Adults)

    Limerick

  • University Hospital Limerick (Pediatrics)

    Limerick

Other trials in Ireland

Australia6 sites

  • Royal Prince Alfred Hospital

    Camperdown

  • The Prince Charles Hospital

    Chermside

  • Alfred Hospital

    Melbourne, VIC

  • Mater Adult Hospital

    South Brisbane

  • Queensland Children's Hospital

    South Brisbane

  • Westmead Hospital

    Westmead

Other trials in Australia

New Zealand4 sites

  • Greenlane Clinical Centre

    Auckland

  • Starship Children's Hospital

    Auckland

  • Canterbury Respiratory Research Group

    Christchurch Hospital

  • Waikato Hospital

    Hamilton

Other trials in New Zealand

Israel3 sites

  • Hadassah University Hospital Mount Scopus

    Jerusalem

  • Schneider Children's Medical Center of Israel

    Petach Tikvah

  • Sheba Medical Center - The Edmond and Lili Safra Children's Hospital

    Tel Litwinsky

Other trials in Israel

Portugal3 sites

  • Hospital de Santa Maria

    Lisbon

  • CHP - Hospital de Santo Antonio

    Porto

  • Hospital Sao Joao

    Porto

Other trials in Portugal

Sweden3 sites

  • Sahlgrenska Universitetssjukhuset

    Gothenburg

  • Lund University Skanes Universitetssjukhus

    Malmö

  • Karolinska Universitetssjukhuset, Huddinge

    Stockholm

Other trials in Sweden

Czechia2 sites

  • Klinika Detskych Infekcnich Nemoci

    Brno

  • Fakultni nemocnice v Motole

    Prague

Other trials in Czechia

Hungary2 sites

  • National Koranyi Institute for TBC and Pulmonology

    Budapest

  • Pulmonology Institute Torokbalint

    Törökbálint

Other trials in Hungary

About this study

Official title: A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-121 Combination Therapy in Subjects With Cystic Fibrosis (CF) Who Are Heterozygous for F508del and a Minimal Function Mutation (F/MF)

The purpose of this study evaluates the efficacy and safety of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF participants who were heterozygous for F508del and a minimal function mutation (F/MF participants).

Conditions
Cystic Fibrosis
Being tested
VX-121/TEZ/D-IVA, ELX/TEZ/IVA, IVA, Placebo (matched to VX-121/TEZ/D-IVA), Placebo (matched to ELX/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.

  • VX-121/TEZ/D-IVADrug

    Also called VX-121/VX-661/CTP-656, VX-121/VX-661/VX-561, VX-121/tezacaftor/deutivacaftor

    Fixed-dose combination tablets for oral administration.

  • ELX/TEZ/IVADrug

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

    Fixed-dose combination tablets for oral administration.

  • IVADrug

    Also called VX-770, ivacaftor

    Tablet for oral administration.

  • Placebo (matched to VX-121/TEZ/D-IVA)Drug

    Placebo matched to VX-121/TEZ/D-IVA for oral administration.

  • Placebo (matched to ELX/TEZ/IVA)Drug

    Placebo matched to ELX/TEZ/IVA for oral administration.

  • Placebo (matched to IVA)Drug

    Placebo matched to IVA for oral administration.

Study groups in NCT05033080
Study groupRoleWhat they receive
ELX/TEZ/IVAActive comparatorFollowing elexacftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) run-in period of 4 weeks, participants received ELX 200 milligram (mg) once daily (qd) /TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the treatment period for 52 weeks.
Receives: Drug: ELX/TEZ/IVA; Drug: IVA; Drug: Placebo (matched to VX-121/TEZ/D-IVA)
VX-121/TEZ/D-IVAExperimentalFollowing ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.
Receives: Drug: VX-121/TEZ/D-IVA; Drug: Placebo (matched to ELX/TEZ/IVA); Drug: Placebo (matched to 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 Through Week 24

Secondary outcomes (3)

  1. Absolute Change in Sweat Chloride (SwCl)

    Sweat samples were collected using an approved collection device.

    Measured: From Baseline Through Week 24

  2. Percentage of Participants With SwCl <60 mmol/L (Pooled With Data From Study VX20-121-103)

    Sweat samples were collected using an approved collection device.

    Measured: From Baseline Through Week 24

  3. Percentage of Participants With SwCl <30 mmol/L (Pooled With Data From Study VX20-121-103)

    Sweat samples were collected using an approved collection device.

    Measured: From Baseline Through Week 24

Timeline

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

  1. First posted2 Sep 2021
  2. Study start14 Sep 2021
  3. Primary completion12 May 2023
  4. Study completion21 Nov 2023

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
435 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05033080
Sponsor's protocol ID
VX20-121-102
Other IDs
2021-000712-31
Status last verified
Sep 2024
First submitted
26 Aug 2021
Last updated
3 Oct 2024
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

Publications

  • Keating C, Yonker LM, Vermeulen F, Prais D, Linnemann RW, Trimble A, Kotsimbos T, Mermis J, Braun AT, O'Carroll M, Sutharsan S, Ramsey B, Mall MA, Taylor-Cousar JL, McKone EF, Tullis E, Floreth T, Michelson P, Sosnay PR, Nair N, Zahigian R, Martin H, Ahluwalia N, Lam A, Horsley A; VX20-121-102 Study Group; VX20-121-103 Study Group. Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials. Lancet Respir Med. 2025 Mar;13(3):256-271. doi: 10.1016/S2213-2600(24)00411-9. Epub 2025 Jan 2.

    PubMed 39756424

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing VX-121/TEZ/D-IVA, ELX/TEZ/IVA and IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 139 sites in 12 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 5 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 3 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 139 sites in United States, United Kingdom, Germany, Spain, Ireland and 7 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 10 Jun 2024). 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 Through Week 24). 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 NCT05033080, 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 3 Oct 2024.

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

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in