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)

NCT ID: NCT05033080

Last Updated: 2024-10-03

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

435 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-14

Study Completion Date

2023-11-21

Brief Summary

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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).

Detailed Description

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Conditions

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Cystic Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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ELX/TEZ/IVA

Following 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.

Group Type ACTIVE_COMPARATOR

ELX/TEZ/IVA

Intervention Type DRUG

Fixed-dose combination tablets for oral administration.

IVA

Intervention Type DRUG

Tablet for oral administration.

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

Intervention Type DRUG

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

VX-121/TEZ/D-IVA

Following 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.

Group Type EXPERIMENTAL

VX-121/TEZ/D-IVA

Intervention Type DRUG

Fixed-dose combination tablets for oral administration.

Placebo (matched to ELX/TEZ/IVA)

Intervention Type DRUG

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

Placebo (matched to IVA)

Intervention Type DRUG

Placebo matched to IVA for oral administration.

Interventions

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VX-121/TEZ/D-IVA

Fixed-dose combination tablets for oral administration.

Intervention Type DRUG

ELX/TEZ/IVA

Fixed-dose combination tablets for oral administration.

Intervention Type DRUG

IVA

Tablet for oral administration.

Intervention Type DRUG

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

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

Intervention Type DRUG

Placebo (matched to ELX/TEZ/IVA)

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

Intervention Type DRUG

Placebo (matched to IVA)

Placebo matched to IVA for oral administration.

Intervention Type DRUG

Other Intervention Names

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VX-121/VX-661/CTP-656 VX-121/VX-661/VX-561 VX-121/tezacaftor/deutivacaftor VX-445/VX-661/VX-770 elexacaftor/tezacaftor/ivacaftor VX-770 ivacaftor

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Banner University of Arizona Medical Center

Tucson, Arizona, United States

Site Status

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

Miller Children's Hospital / Long Beach Memorial

Long Beach, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Kaiser Permanente

Oakland, California, United States

Site Status

University of California Davis Medical Center

Sacramento, California, United States

Site Status

University of California San Francisco, Lung Transplant Program

San Francisco, California, United States

Site Status

Children's Hospital of Colorado

Aurora, Colorado, United States

Site Status

National Jewish Health

Denver, Colorado, United States

Site Status

University of Florida, Shands Hospital

Gainesville, Florida, United States

Site Status

Joe DiMaggio Cystic Fibrosis & Pulmonary Center

Hollywood, Florida, United States

Site Status

Central Florida Pulmonary Group, PA

Orlando, Florida, United States

Site Status

Nemours Children's Hospital

Orlando, Florida, United States

Site Status

Johns Hopkins All Children's Hospital Outpatient Care Center

St. Petersburg, Florida, United States

Site Status

The Emory Clinic at Chantilly

Atlanta, Georgia, United States

Site Status

Augusta University

Augusta, Georgia, United States

Site Status

St. Luke's Cystic Fibrosis Center of Idaho

Boise, Idaho, United States

Site Status

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

Chicago, Illinois, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

Riley Hospital for Children at Indiana University Health

Indianapolis, Indiana, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Kosair Charities Pediatric Clinical Research Unit

Louisville, Kentucky, United States

Site Status

Tulane Medical Center

New Orleans, Louisiana, United States

Site Status

Massachusetts General Hospital Cystic Fibrosis Center Clinical Rsearch Center

Boston, Massachusetts, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

UMass Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

Michigan Medicine

Ann Arbor, Michigan, United States

Site Status

Helen DeVos Children's Hospital CF Center

Grand Rapids, Michigan, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Childrens Hospital University of Missouri Health Sciences Center

Columbia, Missouri, United States

Site Status

The Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Cardinal Glennon Children's Hospital - St. Louis University

St Louis, Missouri, United States

Site Status

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

St Louis, Missouri, United States

Site Status

Billings Clinic

Billings, Montana, United States

Site Status

Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Dartmouth Hitchcock, Manchester

Manchester, New Hampshire, United States

Site Status

Morristown Medical Center

Morristown, New Jersey, United States

Site Status

Albany Medical College

Albany, New York, United States

Site Status

CF Therapeutics Development Center of Western New York

Buffalo, New York, United States

Site Status

Northwell Health- Long Island Jewish Medical Center

New Hyde Park, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Atrium Health Levine Children's Hospital

Charlotte, North Carolina, United States

Site Status

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Site Status

Cleveland Clinic CF

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Dayton Children's Hospital

Dayton, Ohio, United States

Site Status

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

Toledo, Ohio, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Sanford Children's Speciality Clinic

Sioux Falls, South Dakota, United States

Site Status

University of Tennessee Medical Center

Knoxville, Tennessee, United States

Site Status

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

Memphis, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Driscoll Children's Hospital

Corpus Christi, Texas, United States

Site Status

The University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Cook Children's Health Care System

Fort Worth, Texas, United States

Site Status

Texas Children's Hospital - Baylor College of Medicine

Houston, Texas, United States

Site Status

University of Utah - Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

Vermont Lung Center

Colchester, Vermont, United States

Site Status

University of Virginia Health System

Charlottesville, Virginia, United States

Site Status

Inova Fairfax

Falls Church, Virginia, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

Royal Prince Alfred Hospital

Camperdown, , Australia

Site Status

The Prince Charles Hospital

Chermside, , Australia

Site Status

Alfred Hospital

Melbourne, VIC, , Australia

Site Status

Mater Adult Hospital

South Brisbane, , Australia

Site Status

Queensland Children's Hospital

South Brisbane, , Australia

Site Status

Westmead Hospital

Westmead, , Australia

Site Status

Klinika Detskych Infekcnich Nemoci

Brno, , Czechia

Site Status

Fakultni nemocnice v Motole

Prague, , Czechia

Site Status

Charite Paediatric Pulmonology Department

Berlin, , Germany

Site Status

St. Josef-Hospital

Bochum, , Germany

Site Status

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

Erlangen, , Germany

Site Status

Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen

Essen, , Germany

Site Status

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

Essen, , Germany

Site Status

Johann Wolfgang Goethe University

Frankfurt, , Germany

Site Status

Hannover Medical School

Hanover, , Germany

Site Status

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status

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

Jena, , Germany

Site Status

Johannes Gutenberg-Universitaet

Mainz, , Germany

Site Status

Klinikum Innenstadt, University of Munich

München, , Germany

Site Status

Pneumologisches Studienzentrum Muenchen-West

München, , Germany

Site Status

Klinikum Westbrandenburg (CF)

Potsdam, , Germany

Site Status

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

Ulm, , Germany

Site Status

Universitätsklinikum Würzburg

Würzburg, , Germany

Site Status

National Koranyi Institute for TBC and Pulmonology

Budapest, , Hungary

Site Status

Pulmonology Institute Torokbalint

Törökbálint, , Hungary

Site Status

Cork University Hospital

Cork, , Ireland

Site Status

Children's Health Ireland at Crumlin

Dublin, , Ireland

Site Status

Children's Health Ireland at Tallaght

Dublin, , Ireland

Site Status

Children's Health Ireland at Temple Street

Dublin, , Ireland

Site Status

St. Vincent's University Hospital

Dublin, , Ireland

Site Status

University Hospital Limerick (Adults)

Limerick, , Ireland

Site Status

University Hospital Limerick (Pediatrics)

Limerick, , Ireland

Site Status

Hadassah University Hospital Mount Scopus

Jerusalem, , Israel

Site Status

Schneider Children's Medical Center of Israel

Petach Tikvah, , Israel

Site Status

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

Tel Litwinsky, , Israel

Site Status

Greenlane Clinical Centre

Auckland, , New Zealand

Site Status

Starship Children's Hospital

Auckland, , New Zealand

Site Status

Canterbury Respiratory Research Group

Christchurch Hospital, , New Zealand

Site Status

Waikato Hospital

Hamilton, , New Zealand

Site Status

Hospital de Santa Maria

Lisbon, , Portugal

Site Status

CHP - Hospital de Santo Antonio

Porto, , Portugal

Site Status

Hospital Sao Joao

Porto, , Portugal

Site Status

Hospital Saint Joan de Deu

Barcelona, , Spain

Site Status

Hospital Universitari Vall d Hebron

Barcelona, , Spain

Site Status

Hospital Infantil Universitario Nino Jesus

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status

Hospital Virgen de la Arrixaca

Murcia, , Spain

Site Status

Corporacio Sanitaria Parc Tauli - Sabadell Hospital Universitari

Sabadell, , Spain

Site Status

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Hospital Universitario y Politecnico La Fe

Valencia, , Spain

Site Status

Sahlgrenska Universitetssjukhuset

Gothenburg, , Sweden

Site Status

Lund University Skanes Universitetssjukhus

Malmo, , Sweden

Site Status

Karolinska Universitetssjukhuset, Huddinge

Stockholm, , Sweden

Site Status

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Site Status

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

Bristol, , United Kingdom

Site Status

Royal Papworth Hospital NHS Foundation Trust

Cambridge, , United Kingdom

Site Status

Royal Hospital for Sick Children

Edinburgh, , United Kingdom

Site Status

Western General Hospital

Edinburgh, , United Kingdom

Site Status

Royal Devon and Exeter Hospital

Exeter, , United Kingdom

Site Status

Clinical Research Facility, Queen Elizabeth University Hospital

Glasgow, , United Kingdom

Site Status

St. James University Hospital

Leeds, , United Kingdom

Site Status

Liverpool Heart and Chest Hospital

Liverpool, , United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

Royal Brompton Hospital

London, , United Kingdom

Site Status

St. Bartholomew's Hospital

London, , United Kingdom

Site Status

Wythenshawe Hospital

Manchester, , United Kingdom

Site Status

Clinical Research Facility

Newcastle upon Tyne, , United Kingdom

Site Status

All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough

Penarth, , United Kingdom

Site Status

Southampton General Hospital

Southampton, , United Kingdom

Site Status

Countries

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United States Australia Czechia Germany Hungary Ireland Israel New Zealand Portugal Spain Sweden United Kingdom

References

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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.

Reference Type DERIVED
PMID: 39756424 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37983082 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2021-000712-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VX20-121-102

Identifier Type: -

Identifier Source: org_study_id

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