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)

Cystic Fibrosis Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05033080
• Other study ID #: VX20-121-102
• Secondary ID: 2021-000712-31
• Status: Completed
• Phase: Phase 3
• Start date: September 14, 2021
• Est. completion date: November 21, 2023

Study information

• Verified date: December 2023
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 436
• Est. completion date: November 21, 2023
• Est. primary completion date: May 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• VX-121/TEZ/D-IVA
Fixed-dose combination tablets for oral administration.
• ELX/TEZ/IVA
Fixed-dose combination tablets for oral administration.
• IVA
Tablet for oral administration.
• Placebo (matched to VX-121/TEZ/D-IVA)
Placebo matched to VX-121/TEZ/D-IVA for oral administration.
• Placebo (matched to ELX/TEZ/IVA)
Placebo matched to ELX/TEZ/IVA for oral administration.
• Placebo (matched to IVA)
Placebo matched to IVA for oral administration.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24		From Baseline Through Week 24
Secondary	Absolute Change From Baseline in Sweat Chloride (SwCl) Through Week 24		From Baseline Through Week 24
Secondary	Proportion of Participants With SwCl <60 Millimole per Liter (mmol/L) Through Week 24 (Pooled With Data From Study VX20-121-103)		From Baseline Through Week 24
Secondary	Proportion of Participants With SwCl <30 mmol/L Through Week 24 (Pooled With Data From Study VX20-121-103)		From Baseline Through Week 24