Clinical trial NCT05033080: 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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2021-09-02
Enrollment: 435
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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

Primary outcomes:
measure: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
timeFrame: From Baseline Through Week 24
Secondary outcomes:
measure: Absolute Change in Sweat Chloride (SwCl)
timeFrame: From Baseline Through Week 24
measure: Percentage of Participants With SwCl <60 mmol/L (Pooled With Data From Study VX20-121-103)
timeFrame: From Baseline Through Week 24
measure: Percentage of Participants With SwCl <30 mmol/L (Pooled With Data From Study VX20-121-103)
timeFrame: From Baseline Through Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: Banner University of Arizona Medical Center
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Long Beach
country: United States
facility: Miller Children's Hospital / Long Beach Memorial
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Oakland
country: United States
facility: Kaiser Permanente
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco, Lung Transplant Program
state: California
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Gainesville
country: United States
facility: University of Florida, Shands Hospital
state: Florida
city: Hollywood
country: United States
facility: Joe DiMaggio Cystic Fibrosis & Pulmonary Center
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary Group, PA
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital Outpatient Care Center
state: Florida
city: Atlanta
country: United States
facility: The Emory Clinic at Chantilly
state: Georgia
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Boise
country: United States
facility: St. Luke's Cystic Fibrosis Center of Idaho
state: Idaho
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Indianapolis
country: United States
facility: Riley Hospital for Children at Indiana University Health
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Kosair Charities Pediatric Clinical Research Unit
state: Kentucky
city: New Orleans
country: United States
facility: Tulane Medical Center
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital Cystic Fibrosis Center Clinical Rsearch Center
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Medicine
state: Michigan
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital CF Center
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Columbia
country: United States
facility: Childrens Hospital University of Missouri Health Sciences Center
state: Missouri
city: Kansas City
country: United States
facility: The Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Cardinal Glennon Children's Hospital - St. Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine / St. Louis Children's Hospital
state: Missouri
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Omaha
country: United States
facility: Nebraska Medical Center
state: Nebraska
city: Manchester
country: United States
facility: Dartmouth Hitchcock, Manchester
state: New Hampshire
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Buffalo
country: United States
facility: CF Therapeutics Development Center of Western New York
state: New York
city: New Hyde Park
country: United States
facility: Northwell Health- Long Island Jewish Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Charlotte
country: United States
facility: Atrium Health Levine Children's Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic CF
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: Dayton Children's Hospital
state: Ohio
city: Toledo
country: United States
facility: ProMedica Toledo Hospital/Toledo Children's Hospital/Pediatric Pulmonary & Cystic Fibrosis Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Children's Speciality Clinic
state: South Dakota
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Memphis
country: United States
facility: Children's Foundation Research Center / Le Bonheur Children's Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Corpus Christi
country: United States
facility: Driscoll Children's Hospital
state: Texas
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Health Care System
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital - Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah - Primary Children's Medical Center
state: Utah
city: Colchester
country: United States
facility: Vermont Lung Center
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Falls Church
country: United States
facility: Inova Fairfax
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
city: Chermside
country: Australia
facility: The Prince Charles Hospital
city: Melbourne, VIC
country: Australia
facility: Alfred Hospital
city: South Brisbane
country: Australia
facility: Mater Adult Hospital
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Brno
country: Czechia
facility: Klinika Detskych Infekcnich Nemoci
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Berlin
country: Germany
facility: Charite Paediatric Pulmonology Department
city: Bochum
country: Germany
facility: St. Josef-Hospital
city: Erlangen
country: Germany
facility: Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital
city: Essen
country: Germany
facility: Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
city: Essen
country: Germany
facility: Universitatsklinikum Essen (AoR), Kinderklinik III, Abt. fur Pneumologie
city: Frankfurt
country: Germany
facility: Johann Wolfgang Goethe University
city: Hannover
country: Germany
facility: Hannover Medical School
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Jena
country: Germany
facility: Mukoviszidose-Zentrum am Universitätsklinikum Jena, Klinik für Kinder- und Jugendmedizin
city: Mainz
country: Germany
facility: Johannes Gutenberg-Universitaet
city: Muenchen
country: Germany
facility: Pneumologisches Studienzentrum Muenchen-West
city: München
country: Germany
facility: Klinikum Innenstadt, University of Munich
city: Potsdam
country: Germany
facility: Klinikum Westbrandenburg (CF)
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm, Klinik für Kinder- und Jugendmedizin (CF)
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
city: Budapest
country: Hungary
facility: National Koranyi Institute for TBC and Pulmonology
city: Torokbalint
country: Hungary
facility: Pulmonology Institute Torokbalint
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Children's Health Ireland at Crumlin
city: Dublin
country: Ireland
facility: Children's Health Ireland at Tallaght
city: Dublin
country: Ireland
facility: Children's Health Ireland at Temple Street
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital
city: Limerick
country: Ireland
facility: University Hospital Limerick (Adults)
city: Limerick
country: Ireland
facility: University Hospital Limerick (Pediatrics)
city: Jerusalem
country: Israel
facility: Hadassah University Hospital Mount Scopus
city: Petach Tikvah
country: Israel
facility: Schneider Children's Medical Center of Israel
city: Tel HaShomer
country: Israel
facility: Sheba Medical Center - The Edmond and Lili Safra Children's Hospital
city: Auckland
country: New Zealand
facility: Greenlane Clinical Centre
city: Auckland
country: New Zealand
facility: Starship Children's Hospital
city: Christchurch Hospital
country: New Zealand
facility: Canterbury Respiratory Research Group
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Lisbon
country: Portugal
facility: Hospital de Santa Maria
city: Porto
country: Portugal
facility: CHP - Hospital de Santo Antonio
city: Porto
country: Portugal
facility: Hospital Sao Joao
city: Barcelona
country: Spain
facility: Hospital Saint Joan de Deu
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Nino Jesus
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Murcia
country: Spain
facility: Hospital Virgen de la Arrixaca
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli - Sabadell Hospital Universitari
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Malmoe
country: Sweden
facility: Lund University Skanes Universitetssjukhus
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset, Huddinge
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol and Weston NHS Foundation Trust, Bristol Royal Hospital
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital NHS Foundation Trust
city: Edinburgh
country: United Kingdom
facility: Royal Hospital for Sick Children
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
city: Glasgow
country: United Kingdom
facility: Clinical Research Facility, Queen Elizabeth University Hospital
city: Leeds
country: United Kingdom
facility: St. James University Hospital
city: Liverpool
country: United Kingdom
facility: Liverpool Heart and Chest Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: London
country: United Kingdom
facility: St. Bartholomew's Hospital
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Clinical Research Facility
city: Penarth
country: United Kingdom
facility: All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
References: