Clinical trial NCT03537651: A Study to Evaluate the Safety and Efficacy of Long-term Treatment With TEZ/IVA in CF Participants With an F508del CFTR Mutation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2018-05-25
Enrollment: 130
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Week 100
Secondary outcomes:
measure: Part A: Absolute Change in Lung Clearance Index2.5 (LCI2.5) for 115/116 FAS (TEZ/IVA Group)
timeFrame: From Parent Study 115 Baseline at Week 96 (Study 116)
measure: Part A: Absolute Change in LCI2.5 for 113B/116 LCI FAS
timeFrame: From Parent Study 113B Baseline at Week 96 (Study 116)
measure: Part A: Absolute Change in Sweat Chloride (SwCl) for 115/116 FAS (TEZ/IVA Group)
timeFrame: From Parent Study 115 Baseline at Week 96 (Study 116)
measure: Part A: Absolute Change in SwCl for 113B/116 FAS
timeFrame: From Parent Study 113B Baseline at Week 96 (Study 116)
measure: Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 115/116 FAS (TEZ/IVA Group)
timeFrame: From Parent Study 115 Baseline at Week 96 (Study 116)
measure: Part A: Absolute Change in CFQ-R Respiratory Domain Score for 113B/116 FAS
timeFrame: From Parent Study 113B Baseline at Week 96 (Study 116)
measure: Part A: Absolute Change in Body Mass Index (BMI) for 115/116 FAS (TEZ/IVA Group)
timeFrame: From Parent Study 115 Baseline at Week 96 (Study 116)
measure: Part A: Absolute Change in BMI for 113B/116 FAS
timeFrame: From Parent Study 113B Baseline at Week 96 (Study 116)
measure: Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Week 192
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Anchorage
country: United States
facility: Providence Alaska Medical Center
state: Alaska
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Wilmington
country: United States
facility: Nemours/ Alfred I. duPont Hospital for Children
state: Delaware
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital Outpatient Care Center
state: Florida
city: Atlanta
country: United States
facility: Center for Advanced Pediatrics
state: Georgia
city: Boise
country: United States
facility: St. Luke's CF Center of Idaho
state: Idaho
city: Indianapolis
country: United States
facility: Riley Hospital for Children Indiana University Health
state: Indiana
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Children's Hospital & Clinics of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: The Children's Mercy Hospital
state: Missouri
city: Manchester
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Buffalo
country: United States
facility: UBMD Pediatrics/ CF Center of Western New York
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford Children's Speciality Clinic
state: South Dakota
city: Austin
country: United States
facility: Austin Children's Chest Associates
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Nedlands
country: Australia
facility: Perth Children's Hospital
city: New Lambton
country: Australia
facility: John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital
city: South Brisbane
country: Australia
facility: Lady Cilento Children's Hospital
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel - Campus Jette
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
city: Vancouver
country: Canada
facility: British Columbia's Children's Hospital
state: British Columbia
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre, Glen Site, Montreal Children's Hospital
state: Quebec
city: Copenhagen
country: Denmark
facility: Juliane Marie Center, Rigshopitalet
city: Bordeaux cedex
country: France
facility: Groupe Hospitaler Pellegrin, CHU De Bordeaux
city: Paris Cedex 15
country: France
facility: Hopital Necker, Enfants Malades
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt
country: Germany
facility: Clinic of J.W. Goethe University
city: Giessen
country: Germany
facility: Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Jena
country: Germany
facility: Universitaetsklinikum Jena, Mukoviszidose-Zentrum
city: Koeln
country: Germany
facility: Universitaetsklinkum Koeln, CF-Studienzentrum
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin
city: Dublin
country: Ireland
facility: Our Lady's Children's Hospital
city: Limerick
country: Ireland
facility: University Hospital Limerick
city: Lomianki
country: Poland
facility: Klinika Mukowiscydozy IMD Oddozial Chorob Pluc Szpzoz IM. Dzieci WarszaWY
city: Bern
country: Switzerland
facility: Inselspital - Universitaetsspital Bern
city: Zürich
country: Switzerland
facility: Kinderspital Zuerich
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: London
country: United Kingdom
facility: Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
References:
citation: Sawicki GS, Chilvers M, McNamara J, Naehrlich L, Saunders C, Sermet-Gaudelus I, Wainwright CE, Ahluwalia N, Campbell D, Harris RS, Paz-Diaz H, Shih JL, Davies JC. A Phase 3, open-label, 96-week trial to study the safety, tolerability, and efficacy of tezacaftor/ivacaftor in children >/= 6 years of age homozygous for F508del or heterozygous for F508del and a residual function CFTR variant. J Cyst Fibros. 2022 Jul;21(4):675-683. doi: 10.1016/j.jcf.2022.02.003. Epub 2022 Feb 18.
citation: Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.