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)

September 18, 2024 updated by: Vertex Pharmaceuticals Incorporated

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

435

Phase

  • Phase 3

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
      • Camperdown, Australia
        • Royal Prince Alfred Hospital
      • Chermside, Australia
        • The Prince Charles Hospital
      • Melbourne, VIC, Australia
        • Alfred Hospital
      • South Brisbane, Australia
        • Queensland Children's Hospital
      • South Brisbane, Australia
        • Mater Adult Hospital
      • Westmead, Australia
        • Westmead Hospital
  • Czechia
      • Brno, Czechia
        • Klinika Detskych Infekcnich Nemoci
      • Praha 5, Czechia
        • Fakultni nemocnice v Motole
  • Germany
      • Berlin, Germany
        • Charite Paediatric Pulmonology Department
      • Bochum, Germany
        • St. Josef-Hospital
      • Erlangen, Germany
        • Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital
      • Essen, Germany
        • Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
      • Essen, Germany
        • Universitatsklinikum Essen (AoR), Kinderklinik III, Abt. fur Pneumologie
      • Frankfurt, Germany
        • Johann Wolfgang Goethe University
      • Hannover, Germany
        • Medizinische Hochschule Hannover
      • Hannover, Germany
        • Hannover Medical School
      • Jena, Germany
        • Mukoviszidose-Zentrum am Universitätsklinikum Jena, Klinik für Kinder- und Jugendmedizin
      • Mainz, Germany
        • Johannes Gutenberg-Universitaet
      • Muenchen, Germany
        • Pneumologisches Studienzentrum Muenchen-West
      • München, Germany
        • Klinikum Innenstadt, University of Munich
      • Potsdam, Germany
        • Klinikum Westbrandenburg (CF)
      • Ulm, Germany
        • Universitätsklinikum Ulm, Klinik für Kinder- und Jugendmedizin (CF)
      • Würzburg, Germany
        • Universitätsklinikum Würzburg
  • Hungary
      • Budapest, Hungary
        • National Koranyi Institute for TBC and Pulmonology
      • Torokbalint, Hungary
        • Pulmonology Institute Torokbalint
  • Ireland
      • Cork, Ireland
        • Cork University Hospital
      • Dublin, Ireland
        • Children's Health Ireland at Crumlin
      • Dublin, Ireland
        • Children's Health Ireland at Temple Street
      • Dublin, Ireland
        • St. Vincent's University Hospital
      • Dublin, Ireland
        • Children's Health Ireland at Tallaght
      • Limerick, Ireland
        • University Hospital Limerick (Adults)
      • Limerick, Ireland
        • University Hospital Limerick (Pediatrics)
  • Israel
      • Jerusalem, Israel
        • Hadassah University Hospital Mount Scopus
      • Petach Tikvah, Israel
        • Schneider Children's Medical Center of Israel
      • Tel HaShomer, Israel
        • Sheba Medical Center - The Edmond and Lili Safra Children's Hospital
  • New Zealand
      • Auckland, New Zealand
        • Starship Children's Hospital
      • Auckland, New Zealand
        • Greenlane Clinical Centre
      • Christchurch Hospital, New Zealand
        • Canterbury Respiratory Research Group
      • Hamilton, New Zealand
        • Waikato Hospital
  • Portugal
      • Lisbon, Portugal
        • Hospital de Santa Maria
      • Porto, Portugal
        • Hospital Sao Joao
      • Porto, Portugal
        • CHP - Hospital de Santo Antonio
  • Spain
      • Barcelona, Spain
        • Hospital Universitari Vall d Hebron
      • Barcelona, Spain
        • Hospital Saint Joan de Deu
      • Madrid, Spain
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain
        • Hospital Universitario Ramón y Cajal
      • Madrid, Spain
        • Hospital Infantil Universitario Niño Jesús
      • Murcia, Spain
        • Hospital Virgen de la Arrixaca
      • Sabadell, Spain
        • Corporacio Sanitaria Parc Tauli - Sabadell Hospital Universitari
      • Sevilla, Spain
        • Hospital Universitario Virgen del Rocio
      • Valencia, Spain
        • Hospital Universitario y Politécnico La Fe
  • Sweden
      • Göteborg, Sweden
        • Sahlgrenska Universitetssjukhuset
      • Malmoe, Sweden
        • Lund University Skanes Universitetssjukhus
      • Stockholm, Sweden
        • Karolinska Universitetssjukhuset, Huddinge
  • United Kingdom
      • Birmingham, United Kingdom
        • Birmingham Heartlands Hospital
      • Bristol, United Kingdom
        • University Hospitals Bristol and Weston NHS Foundation Trust, Bristol Royal Hospital
      • Cambridge, United Kingdom
        • Royal Papworth Hospital NHS Foundation Trust
      • Edinburgh, United Kingdom
        • Western General Hospital
      • Edinburgh, United Kingdom
        • Royal Hospital for Sick Children
      • Exeter, United Kingdom
        • 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 Hospital
      • London, United Kingdom
        • King's College Hospital
      • London, United Kingdom
        • St. Bartholomew's Hospital
      • Manchester, United Kingdom
        • Wythenshawe Hospital
      • Newcastle Upon Tyne, United Kingdom
        • Clinical Research Facility
      • Penarth, United Kingdom
        • All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
      • 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
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Arkansas Children's Hospital
    • California
      • Long Beach, California, United States, 90806
        • Miller Children's Hospital / Long Beach Memorial
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
      • Oakland, California, United States, 94611
        • Kaiser Permanente
      • 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
      • Aurora, Colorado, United States, 80045
        • Children's Hospital of Colorado
      • Denver, Colorado, United States, 80206
        • National Jewish Health
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida, Shands Hospital
      • Hollywood, Florida, United States, 33021
        • Joe DiMaggio Cystic Fibrosis & Pulmonary Center
      • Orlando, Florida, United States, 32827
        • Nemours Children's Hospital
      • Orlando, Florida, United States, 32803
        • Central Florida Pulmonary Group, PA
      • Saint Petersburg, Florida, United States, 33701
        • Johns Hopkins All Children's Hospital Outpatient Care Center
    • Georgia
      • Atlanta, Georgia, United States, 30324
        • The Emory Clinic at Chantilly
      • Augusta, Georgia, United States, 30912
        • Augusta University
    • Idaho
      • Boise, Idaho, United States, 83702
        • St. Luke's Cystic Fibrosis Center of Idaho
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Ann & Robert H. Lurie Children's Hospital of Chicago
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children at Indiana University Health
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky
      • Louisville, Kentucky, United States, 40202
        • Kosair Charities Pediatric Clinical Research Unit
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cystic Fibrosis Center Clinical Rsearch Center
      • Worcester, Massachusetts, United States, 01655
        • UMass Memorial Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-5212
        • Michigan Medicine
      • Grand Rapids, Michigan, United States, 49503
        • Helen DeVos Children's Hospital CF Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University Of Minnesota
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Columbia, Missouri, United States, 65212
        • Childrens Hospital University of Missouri Health Sciences Center
      • Kansas City, Missouri, United States, 64108
        • The Children's Mercy Hospital
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine / St. Louis Children's Hospital
      • Saint Louis, Missouri, United States, 63104
        • Cardinal Glennon Children's Hospital - St. Louis University
    • Montana
      • Billings, Montana, United States, 59101
        • Billings Clinic
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Nebraska Medical Center
    • New Hampshire
      • Manchester, New Hampshire, United States, 03104
        • Dartmouth Hitchcock, Manchester
    • New Jersey
      • Morristown, New Jersey, United States, 07960
        • Morristown Medical Center
    • New York
      • Albany, New York, United States, 12208
        • Albany Medical College
      • Buffalo, New York, United States, 14203
        • CF Therapeutics Development Center of Western 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
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Atrium Health Levine Children's Hospital
      • Winston-Salem, North Carolina, United States, 27104
        • Wake Forest Baptist Health
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic CF
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital
      • Dayton, Ohio, United States, 45404
        • Dayton Children's Hospital
      • Toledo, Ohio, United States, 43606
        • ProMedica Toledo Hospital/Toledo Children's Hospital/Pediatric Pulmonary & Cystic Fibrosis 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
        • UPMC Children's Hospital of Pittsburgh
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57105
        • Sanford Children's Speciality Clinic
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • University of Tennessee Medical Center
      • Memphis, Tennessee, United States, 38105
        • Children's Foundation Research Center / Le Bonheur Children's Hospital
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Corpus Christi, Texas, United States, 78411
        • Driscoll Children's Hospital
      • Dallas, Texas, United States, 75390-8558
        • The University of Texas Southwestern Medical Center
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Health Care System
      • Houston, Texas, United States, 77030
        • Texas Children's Hospital - Baylor College of Medicine
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah - Primary Children's Medical Center
    • Vermont
      • Colchester, Vermont, United States, 05446
        • Vermont Lung Center
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System
      • Falls Church, Virginia, United States, 22042
        • Inova Fairfax
    • 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

Ages Eligible for Study

8 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key 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

Key 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

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
Intervention / Treatment
Active Comparator: 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.
Drug: IVA
Tablet for oral administration.
Other Names:
  • VX-770
  • ivacaftor
Drug: ELX/TEZ/IVA
Fixed-dose combination tablets for oral administration.
Other Names:
  • VX-445/VX-661/VX-770
  • elexacaftor/tezacaftor/ivacaftor
Drug: Placebo (matched to VX-121/TEZ/D-IVA)
Placebo matched to VX-121/TEZ/D-IVA for oral administration.
Experimental: 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.
Drug: VX-121/TEZ/D-IVA
Fixed-dose combination tablets for oral administration.
Other Names:
  • VX-121/VX-661/CTP-656
  • VX-121/VX-661/VX-561
  • VX-121/tezacaftor/deutivacaftor
Drug: Placebo (matched to ELX/TEZ/IVA)
Placebo matched to ELX/TEZ/IVA for oral administration.
Drug: Placebo (matched to IVA)
Placebo matched to IVA for oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Time Frame: From Baseline Through Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline Through Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Absolute Change in Sweat Chloride (SwCl)
Time Frame: From Baseline Through Week 24
Sweat samples were collected using an approved collection device.
From Baseline Through Week 24
Percentage of Participants With SwCl <60 mmol/L (Pooled With Data From Study VX20-121-103)
Time Frame: From Baseline Through Week 24
Sweat samples were collected using an approved collection device.
From Baseline Through Week 24
Percentage of Participants With SwCl <30 mmol/L (Pooled With Data From Study VX20-121-103)
Time Frame: From Baseline Through Week 24
Sweat samples were collected using an approved collection device.
From Baseline Through Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vertex Pharmaceuticals Incorporated

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)

September 14, 2021

Primary Completion (Actual)

May 12, 2023

Study Completion (Actual)

November 21, 2023

Study Registration Dates

First Submitted

August 26, 2021

First Submitted That Met QC Criteria

August 26, 2021

First Posted (Actual)

September 2, 2021

Study Record Updates

Last Update Posted (Actual)

October 3, 2024

Last Update Submitted That Met QC Criteria

September 18, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VX20-121-102
  • 2021-000712-31 (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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