A Study to Evaluate the Safety and Efficacy of Long-term Treatment With TEZ/IVA in CF Participants With an F508del CFTR Mutation

Cystic Fibrosis Clinical Trial

Official title:

A Phase 3, Open-label, Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Tezacaftor in Combination With Ivacaftor in Subjects With Cystic Fibrosis Aged 6 Years and Older, Homozygous or Heterozygous for the F508del-CFTR Mutation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03537651
• Other study ID #: VX17-661-116
• Secondary ID: 2017-002968-40
• Status: Completed
• Phase: Phase 3
• Start date: April 25, 2018
• Est. completion date: September 29, 2023

Study information

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

Clinical Trial Summary

This study evaluates the long-term safety and tolerability of tezacaftor in combination with ivacaftor (TEZ/IVA) in participants with cystic fibrosis (CF) aged 6 years and older, homozygous or heterozygous for the F508del mutation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: September 29, 2023
• Est. primary completion date: October 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

Inclusion Criteria:

• Completed the Week 24 Visit in Study 113 Part B or the Week 8 Visit in Study 115

• Eligible CFTR Mutation

Exclusion Criteria:

• Pregnant and nursing females

• History of poor compliance with study drug and/or procedures in a previous study as deemed by the investigator

• Ongoing participation in another study with investigational drug

Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

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

Locations

Country	Name	City	State
Australia	Perth Children's Hospital	Nedlands
Australia	John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital	New Lambton
Australia	Lady Cilento Children's Hospital	South Brisbane
Australia	The Children's Hospital at Westmead	Westmead
Belgium	Universitair Ziekenhuis Brussel - Campus Jette	Brussels
Belgium	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven
Canada	McGill University Health Centre, Glen Site, Montreal Children's Hospital	Montreal	Quebec
Canada	The Hospital for Sick Children	Toronto	Ontario
Canada	British Columbia's Children's Hospital	Vancouver	British Columbia
Denmark	Juliane Marie Center, Rigshopitalet	Copenhagen
France	Groupe Hospitaler Pellegrin, CHU De Bordeaux	Bordeaux cedex
France	Hopital Necker, Enfants Malades	Paris Cedex 15
Germany	Universitätsklinikum Essen	Essen
Germany	Clinic of J.W. Goethe University	Frankfurt
Germany	Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin	Giessen
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitaetsklinikum Jena, Mukoviszidose-Zentrum	Jena
Germany	Universitaetsklinkum Koeln, CF-Studienzentrum	Koeln
Germany	Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin	Tuebingen
Ireland	Our Lady's Children's Hospital	Dublin
Ireland	University Hospital Limerick	Limerick
Poland	Klinika Mukowiscydozy IMD Oddozial Chorob Pluc Szpzoz IM. Dzieci WarszaWY	Lomianki
Switzerland	Inselspital - Universitaetsspital Bern	Bern
Switzerland	Kinderspital Zuerich	Zürich
United Kingdom	Leeds General Infirmary	Leeds
United Kingdom	Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital	London
United Kingdom	Southampton General Hospital	Southampton
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Center for Advanced Pediatrics	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Austin Children's Chest Associates	Austin	Texas
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	UBMD Pediatrics/ CF Center of Western New York	Buffalo	New York
United States	Medical University of South Carolina (MUSC)	Charleston	South Carolina
United States	Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Baylor College of Medicine	Houston	Texas
United States	Riley Hospital for Children Indiana University Health	Indianapolis	Indiana
United States	The Children's Mercy Hospital	Kansas City	Missouri
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Dartmouth Hitchcock Medical Center	Manchester	New Hampshire
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Children's Hospital & Clinics of Minnesota	Minneapolis	Minnesota
United States	Columbia University Medical Center	New York	New York
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Johns Hopkins All Children's Hospital Outpatient Care Center	Saint Petersburg	Florida
United States	Seattle Children's Hospital	Seattle	Washington
United States	Sanford Children's Speciality Clinic	Sioux Falls	South Dakota
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Nemours/ Alfred I. duPont Hospital for Children	Wilmington	Delaware
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  France,  Germany,  Ireland,  Poland,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)		Day 1 up to Week 100
Secondary	Part A: Absolute Change in Lung Clearance Index2.5 (LCI2.5) for 115/116 FAS (TEZ/IVA Group)	The LCI2.5 index is the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting values and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured functional residual capacity (FRC). An LCI of 7.5 and below is normal; values greater than 7.5 are abnormal. LCI is able to detect abnormalities in lung function earlier than more traditional modalities such as spirometry.	From Parent Study 115 Baseline at Week 96 (Study 116)
Secondary	Part A: Absolute Change in LCI2.5 for 113B/116 LCI FAS	The LCI2.5 index is the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting values and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured functional residual capacity (FRC). An LCI of 7.5 and below is normal; values greater than 7.5 are abnormal. LCI is able to detect abnormalities in lung function earlier than more traditional modalities such as spirometry.	From Parent Study 113B Baseline at Week 96 (Study 116)
Secondary	Part A: Absolute Change in Sweat Chloride (SwCl) for 115/116 FAS (TEZ/IVA Group)	Sweat samples were collected using an approved collection device.	From Parent Study 115 Baseline at Week 96 (Study 116)
Secondary	Part A: Absolute Change in SwCl for 113B/116 FAS	Sweat samples were collected using an approved collection device.	From Parent Study 113B Baseline at Week 96 (Study 116)
Secondary	Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 115/116 FAS (TEZ/IVA Group)	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.	From Parent Study 115 Baseline at Week 96 (Study 116)
Secondary	Part A: Absolute Change in CFQ-R Respiratory Domain Score for 113B/116 FAS	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.	From Parent Study 113B Baseline at Week 96 (Study 116)
Secondary	Part A: Absolute Change in Body Mass Index (BMI) for 115/116 FAS (TEZ/IVA Group)	BMI was defined as weight in kilograms (kg) divided by squared height in meters (m^2).	From Parent Study 115 Baseline at Week 96 (Study 116)
Secondary	Part A: Absolute Change in BMI for 113B/116 FAS	BMI was defined as weight in kg divided by m^2.	From Parent Study 113B Baseline at Week 96 (Study 116)
Secondary	Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)		Day 1 up to Week 192