A Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy

Cystic Fibrosis Clinical Trial

Official title:

A Phase 3, Open-label Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Homozygous or Heterozygous for the F508del Mutation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03525574
• Other study ID #: VX17-445-105
• Secondary ID: 2018-000185-11
• Status: Completed
• Phase: Phase 3
• Start date: October 9, 2018
• Est. completion date: January 9, 2023

Study information

• Verified date: April 2024
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study evaluates the long-term safety and tolerability of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous or heterozygous for the F508del mutation

Recruitment information / eligibility

• Status: Completed
• Enrollment: 507
• Est. completion date: January 9, 2023
• Est. primary completion date: January 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Completed study drug treatment in a parent study i.e.VX17-445-102 (NCT03525444) and VX17-445-103 (NCT03525548); or had study drug interruption(s) in a parent study but completed study visits up to the last scheduled visit of the Treatment Period in the parent study.

Exclusion Criteria:

• History of drug intolerance in a parent study that would pose an additional risk to the subject in the opinion of the investigator.

• Current participation in an investigational drug trial (other than a parent study)

Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• ELX/TEZ/IVA
Fixed-dose combination (FDC) tablet for oral administration.
• IVA
Tablet for oral administration.

Locations

Country	Name	City	State
Australia	Women & Children's Hospital	North Adelaide
Australia	The Royal Children's Hospital	Parkville
Australia	Mater Misericordiae Ltd	South Brisbane
Australia	The Children's Hospital at Westmead	Westmead
Australia	Westmead Hospital	Westmead
Austria	University of Graz	Graz
Austria	Medizinische Universität Innsbruck	Innsbruck
Austria	LKH - Universitätsklinikum der PMU Salzburg	Salzburg
Austria	Medizinische Universitat Wien	Vienna
Belgium	Cliniques Universitaires de Bruxelles Hopital Erasme	Brussels
Belgium	Universitair Ziekenhuis Brussel - Campus Jette	Brussels
Belgium	UZ Antwerpen	Edegem
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven
Canada	University of Calgary Medical Clinic of the Foothills Medical Centre	Calgary
Canada	McGill University Health Centre, Glen Site, Montreal Children's Hospital	Montreal
Canada	Centre Hospitalier De L'Universite Laval	Quebec City
Canada	The Hospital for Sick Children	Toronto
Canada	British Columbia's Children's Hospital	Vancouver
Canada	St. Paul's Hospital	Vancouver
Czechia	Fakultni Nemocnice Brno	Brno
Czechia	Fakultni nemocnice v Motole	Praha 5
France	Centre Hospitalier Lyon Sud	Benite Cedex
France	Groupe Hospitaler Pellegrin, CHU De Bordeaux	Bordeaux cedex
France	CHU Marseille - Hopital Nord	Marseille
France	CHU de Nice - Hopital Pasteur	Nice
France	Hopital Cochin	Paris
France	CHU de Rouen - Hopital Charles Nicolle	Rouen
France	Hopital Foch (Suresnes), Hopital Foch, Adultes	Suresnes
Germany	Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital	Erlangen
Germany	Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin	Giessen
Germany	Hannover Medical School	Hannover
Germany	Johannes Gutenberg-Universitaet	Mainz
Germany	Dr. von Haunersches Kinderspital	München
Germany	Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin	Tuebingen
Germany	University Hospital Wuerzburg	Wurzburg
Greece	General Hospital of Attika "Sismanoglio"(Adult CF center, NHS)	Maroussi
Italy	Azienda Ospedaliero Universitaria Ospendali Riuniti	Ancona
Italy	Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer	Firenze
Italy	IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico	Genova
Italy	Azienda Ospedaliera Universitaria Policlinico G. Martino	Messina
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	Centro Regionale Fibrosi Cistica, A.O. Ospedale San Carlo	Potenza
Italy	Azienda Ospedaliera di Verona-Ospedale Civile Maggiore	Verona
Netherlands	Academic Medical Center	Amsterdam
Netherlands	HagaZiekenhuis van den Haag	Den Haag
Netherlands	University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis	Heidelberglaan
Netherlands	UMC St. Radboud	Nijmegen
Netherlands	Erasmus Medical Center	Rotterdam
Sweden	Karolinska Universitetssjukhuset, Huddinge	Stockholm
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital	Birmingham
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital	Exeter
United Kingdom	Leeds General Infirmary	Leeds
United Kingdom	King's College Hospital	London
United Kingdom	Royal Manchester Children's Hospital	Manchester
United Kingdom	Southampton General Hospital	Southampton
United States	Akron Children's Hospital	Akron	Ohio
United States	UNM Clinical and Translational Science Center	Albuquerque	New Mexico
United States	Children's Specialty Services at North Druid Hills	Atlanta	Georgia
United States	Augusta University	Augusta	Georgia
United States	Dell Children's Medical Center of Central Texas	Austin	Texas
United States	Billings Clinic Hospital	Billings	Montana
United States	Massachusetts General Hospital Cystic Fibrosis Center Clinical Research Center	Boston	Massachusetts
United States	UNC Marsico Clinical Research Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia Primary Care Center	Charlottesville	Virginia
United States	Ann & Robert Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	UC Health Holmes	Cincinnati	Ohio
United States	Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Vermont Lung Center	Colchester	Vermont
United States	Nationwide Children's Hospital	Columbus	Ohio
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	Harper University Hospital	Detroit	Michigan
United States	University of Florida, Shands Hospital	Gainesville	Florida
United States	Joe DiMaggio Cystic Fibrosis & Pulmonary Center	Hollywood	Florida
United States	Nemours Children's Specialty Care	Jacksonville	Florida
United States	The University of Kansas Medical Center	Kansas City	Kansas
United States	University of Arkansas for Medical Sciences	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	Valley Children's Hospital	Madera	California
United States	University of Wisconsin Hospitals and Clinics	Madison	Wisconsin
United States	CTSI Adult Translational Research Unit/Medical College of Wisconsin/Froedtert Hospital	Milwaukee	Wisconsin
United States	Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota	Minneapolis	Minnesota
United States	West Virginia University	Morgantown	West Virginia
United States	Morristown Medical Center	Morristown	New Jersey
United States	Tulane Medical Center	New Orleans	Louisiana
United States	The Cystic Fibrosis Center, Mount Sinai Beth Israel	New York	New York
United States	Children's Hospital of the King's Daughters	Norfolk	Virginia
United States	Kaiser Permanente	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
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	Cystic Fibrosis Center, Children's Hospital of Illinois at OSF Saint Francis Medical Center	Peoria	Illinois
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Maine Medical Partners	Portland	Maine
United States	Children's Hospital of Richmond at VCU, Children's Pavilion	Richmond	Virginia
United States	University of California Davis Medical Center	Sacramento	California
United States	UCSF Gateway Medical Center	San Francisco	California
United States	University of Washington Medical Center	Seattle	Washington
United States	Tampa General Hospital Cardiac and Lung Transplant Clinic	Tampa	Florida
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

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Czechia,  France,  Germany,  Greece,  Italy,  Netherlands,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment Period: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)		From Day 1 up to Week 196
Secondary	Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 102/105 Efficacy Set	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Secondary	Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/105 Efficacy Set	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Secondary	Absolute Change in Sweat Chloride (SwCl) for 102/105 Efficacy Set	Sweat samples were collected using an approved collection device. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Secondary	Absolute Change in Sweat Chloride (SwCl) for 103/105 Efficacy Set	Sweat samples were collected using an approved collection device. This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Secondary	Number of Pulmonary Exacerbations (PEx) for 102/105 Efficacy Set	Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.	From Baseline at Week 192
Secondary	Number of Pulmonary Exacerbations (PEx) for 103/105 Efficacy Set	Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.	From Baseline at Week 192
Secondary	Time to First PEx for 102/105 Efficacy Set	Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.	From Baseline at Week 192
Secondary	Time to First PEx for 103/105 Efficacy Set	Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.	From Baseline at Week 192
Secondary	Absolute Change in Body Mass Index (BMI) for 102/105 Efficacy Set	BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Secondary	Absolute Change in Body Mass Index (BMI) for 103/105 Efficacy Set	BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Secondary	Absolute Change in BMI Z-score for 102/105 Efficacy Set	BMI was defined as weight in kg divided by height in m^2. Z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Secondary	Absolute Change in BMI Z-score for 103/105 Efficacy Set	BMI was defined as weight in kg divided by height in m^2. Z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI. This analysis set included study 103 parent study participants who received TEZ/IVA-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Secondary	Absolute Change in Body Weight for 102/105 Efficacy Set	This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Secondary	Absolute Change in Body Weight for 103/105 Efficacy Set	This analysis set included study 103 parent study participants who received TEZ/IVA and ELX/TEZ/IVA.	From Baseline at Week 192
Secondary	Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 102/105 Efficacy Set	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. This analysis set included study 102 parent study participants who received Placebo-ELX/TEZ/IVA and ELX/TEZ/IVA-ELX/TEZ/IVA.	From Baseline at Week 192
Secondary	Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/105 Efficacy Set	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. This analysis set included study 103 parent study participants who received TEZ/IVA and ELX/TEZ/IVA.	From Baseline at Week 192