A Study Evaluating the Long Term Safety and Efficacy of VX-659 Combination Therapy

Cystic Fibrosis Clinical Trial

Official title:

A Phase 3, Open-label Study Evaluating the Long Term Safety and Efficacy of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Who Are Homozygous or Heterozygous for the F508del Mutation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03447262
• Other study ID #: VX17-659-105
• Secondary ID: 2017-004134-29
• Status: Terminated
• Phase: Phase 3
• Start date: July 13, 2018
• Est. completion date: September 9, 2020

Study information

• Verified date: December 2021
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the long-term safety and tolerability of VX-659 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: Terminated
• Enrollment: 484
• Est. completion date: September 9, 2020
• Est. primary completion date: September 9, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Completed study drug treatment in a parent study; 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:
• VX-659/TEZ/IVA
Fixed-dose combination tablets for oral administration qd in the morning.
• IVA
IVA tablet qd in the evening.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	The Prince Charles Hospital	Chermside
Australia	Alfred Hospital	Melbourne
Australia	Institute for Respiratory Health, Sir Charles Gairdner Hospital	Nedlands
Australia	John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital	New Lambton
Australia	Telethon Kids Institute	Perth
Australia	Sydney Children's Hospital	Randwick
Australia	Lady Cilento Children's Hospital	South Brisbane
Canada	Stollery Children's Hospital	Edmonton
Canada	Queen Elizabeth II Health Sciences Center	Halifax
Canada	St. Michael's Hospital	Toronto
Denmark	Juliane Marie Center, Rigshospitalet	Copenhagen
Germany	Charite Paediatric Pulmonology Department	Berlin
Germany	Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen	Essen
Germany	Clinic of J.W. Goethe University	Frankfurt
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Mukeviszidose-Zentrum am Universitatsklinikum Jena, Klinik fuer Kinder- und Jugendmedizin	Jena
Germany	Universitaetsklinkum Koeln, CF-Studienzentrum	Koeln
Germany	Universitatsklinikum Schleswig-Holstein, Klinik für Kinder- und Jugendmedizin	Lubeck
Germany	Pneumologische Praxis Pasing	Muenchen
Germany	Klinikum Innenstadt, University of Munich	München
Ireland	Cork University Hospital	Cork
Ireland	Beaumont Hospital	Dublin
Ireland	Our Lady's Children's Hospital	Dublin
Ireland	St. Vincent's University Hospital	Dublin
Ireland	Temple Street Children's University Hospital	Dublin
Ireland	University Hospital Galway	Galway
Ireland	University Hospital Limerick	Limerick
Israel	Lady Davis Carmel Medical Center	Haifa
Israel	Rambam Health Care Campus, Liver Unit	Haifa
Israel	Pediatrics Hadassah Medical Center	Jerusalem
Israel	Schneider Children's Medical Center	Petah Tikva
Israel	Sheba Medical Center	Tel HaShomer
Poland	Klinika Mukowiscydozy IMD Oddozial Chorob Pluc Szpzoz IM. Dzieci WarszaWY	Lomianki
Spain	Hospital Universitari Vall d Hebron	Barcelona
Spain	Hospital Universitari Vall d´Hebron Servicio de Broncoscopia	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Infantil La Paz	Madrid
Spain	Parc Tauli Sabadell Hospital Universitari	Sabadell
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitario y Politecnico La Fe	Valencia
Switzerland	Lindenhofspital - Quartier Bleu	Bern
Switzerland	Kinderspital Zuerich	Zürich
United Kingdom	Papworth Hospital NHS Foundation Trust, Papworth Everard	Cambridge
United Kingdom	Clinical Research Facility, Queen Elizabeth University Hospital	Glasgow
United Kingdom	St. James University Hospital	Leeds
United Kingdom	Liverpool Head and Chest Hospital	Liverpool
United Kingdom	Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital	London
United Kingdom	Wythenshaw e Hospital	Manchester
United Kingdom	The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary	Newcastle Upon Tyne
United Kingdom	Wolfson Cystic Fibrosis Unit, City Campus	Nottingham
United Kingdom	All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough	Penarth
United States	Albany Medical College	Albany	New York
United States	Michigan Medicine	Ann Arbor	Michigan
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	St. Luke's CF Center of Idaho	Boise	Idaho
United States	Boston Children's Hospital	Boston	Massachusetts
United States	CF Therapeutics Development Center of Western New York	Buffalo	New York
United States	Clinical Research of Charlotte	Charlotte	North Carolina
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Cystic Fibrosis Center of Chicago	Glenview	Illinois
United States	Spectrum Health Medical Group Adult Cystic Fibrosis Care Center	Grand Rapids	Michigan
United States	Hartford Hospital	Hartford	Connecticut
United States	Texas Children's Hospital	Houston	Texas
United States	Indiana Clinical Research Center, IU Health University Hospital	Indianapolis	Indiana
United States	The University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	The Children's Mercy Hospital	Kansas City	Missouri
United States	University of Tennessee Medical Center- Adult Cystic Fibrosis Clinic	Knoxville	Tennessee
United States	University of Kentucky	Lexington	Kentucky
United States	Kosair Charities Pediatric Clinical Research Unit	Louisville	Kentucky
United States	Dartmouth Hitchcock, Manchester	Manchester	New Hampshire
United States	Children's Foundation Research Center / Le Bonheur Children's Hospital	Memphis	Tennessee
United States	Nicklaus Children's Hospital	Miami	Florida
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Rutgers-Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Yale New Haven Medical Center	New Haven	Connecticut
United States	Northwell Health, Long Island Jewish Medical Center	New Hyde Park	New York
United States	Columbia University Medical Center	New York	New York
United States	Advocate Children's Hospital - Park Ridge / North Suburban Pulmonary and Critical Care Consultants	Niles	Illinois
United States	Santiago Reyes, M.D.	Oklahoma City	Oklahoma
United States	Orlando Health, Inc.- Arnold Palmer Hospital for Children (APH)	Orlando	Florida
United States	Stanford University	Palo Alto	California
United States	Drexel University College of Medicine / Drexel Adult Cystic Fibrosis Center	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
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	Seattle Children's Hospital	Seattle	Washington
United States	Sanford Children's Specialty Clinic	Sioux Falls	South Dakota
United States	Providence Pediatric Pulmonary & Cystic Fibrosis Clinic	Spokane	Washington
United States	SUNY Upstate Medical University	Syracuse	New York
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,  Canada,  Denmark,  Germany,  Ireland,  Israel,  Poland,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)		From Day 1 up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First in the Current Study 659-105 (up to Week 100)
Secondary	Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for Participants From the Parent Study 659-102	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.	From Baseline at Week 72 (Study 659-105)
Secondary	Absolute Change in ppFEV1 for Participants From the Parent Study 659-103	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.	From Baseline at Week 72 (Study 659-105)
Secondary	Absolute Change in Sweat Chloride (SwCl) for Participants From the Parent Study 659-102	Sweat samples were collected using an approved collection device. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.	From Baseline at Week 24 (Study 659-105)
Secondary	Absolute Change in SwCl for Participants From the Parent Study 659-103	Sweat samples were collected using an approved collection device. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.	From Baseline at Week 24 (Study 659-105)
Secondary	Number of Pulmonary Exacerbations (PEx) for Participants From the Parent Study 659-102	PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-102 or/and VX-659/TEZ/IVA in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline except for Placebo - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.	From Baseline up to Week 96 (Study 659-105)
Secondary	Number of PEx for Participants From the Parent Study 659-103	PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The analysis was planned to be reported for overall participants from the parent study 659-103, that is combined for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-103 or/and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline except for TEZ/IVA - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.	From Baseline up to Week 96 (Study 659-105)
Secondary	Number of Participants With at Least One PEx for Participants From the Parent Study 659-102	PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The time-to-first-PEx data were planned to be estimated using the Kaplan-Meier (KM) method. However, because way less than 50% of participants had events, median time-to-first event data were not estimable. Instead, the number of participants with at least one PEx event was assessed and reported separately for those in Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and the VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-102 or/and VX-659/TEZ/IVA in the current study 659-105). Baseline was defined as the parent study baseline except for Placebo - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.	From Baseline up to Week 96 (Study 659-105)
Secondary	Number of Participants With at Least One PEx for Participants From the Parent Study 659-103	PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The time-to-first-PEx data were planned to be estimated using the KM method. However, because way less than 50% of participants had events, median time-to-first-event data were not estimable. Instead, the number of participants with at least one PEx event was assessed and reported for all participants from the parent study 659-103, that is combined for those in the TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and the VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-103 or/and in the current study 659-105). Baseline was defined as the parent study baseline except for TEZ/IVA - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.	From Baseline up to Week 96 (Study 659-105)
Secondary	Absolute Change in Body Mass Index (BMI) for Participants From the Parent Study 659-102	BMI was defined as weight in kilograms (kg) divided by squared height in meters (m^2). The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.	From Baseline at Week 72 (Study 659-105)
Secondary	Absolute Change in BMI for Participants From the Parent Study 659-103	BMI was defined as weight in kg divided by squared height in meters (m^2). The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.	From Baseline at Week 72 (Study 659-105)
Secondary	Absolute Change in BMI Z-score for Participants From the Parent Study 659-102 (Participants <=20 Years Old at Parent Study Baseline)	BMI was defined as weight in kg divided by squared height in meters (m^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.	From Baseline at Week 60 (Study 659-105)
Secondary	Absolute Change in BMI Z-score for Participants From The Parent Study 659-103 (Participants <=20 Years Old at Parent Study Baseline)	BMI was defined as weight in kg divided by squared height in meters (m^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.	From Baseline at Week 60 (Study 659-105)
Secondary	Absolute Change in Body Weight for Participants From the Parent Study 659-102	The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.	From Baseline at Week 72 (Study 659-105)
Secondary	Absolute Change in Body Weight for Participants From the Parent Study 659-103	The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.	From Baseline at Week 72 (Study 659-105)
Secondary	Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for Participants From the Parent Study 659-102	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. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.	From Baseline at Week 72 (Study 659-105)
Secondary	Absolute Change in CFQ-R Respiratory Domain Score for Participants From the Parent Study 659-103	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. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.	From Baseline at Week 72 (Study 659-105)