search
Back to results

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

Primary Purpose

Cystic Fibrosis

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
TEZ/IVA
IVA
Sponsored by
Vertex Pharmaceuticals Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Alabama at Birmingham
  • Providence Alaska Medical Center
  • Arkansas Children's Hospital
  • Children's Hospital Los Angeles
  • Children's Hospital Colorado
  • Nemours/ Alfred I. duPont Hospital for Children
  • Johns Hopkins All Children's Hospital Outpatient Care Center
  • Center for Advanced Pediatrics
  • St. Luke's CF Center of Idaho
  • Riley Hospital for Children Indiana University Health
  • Boston Children's Hospital
  • Children's Hospital & Clinics of Minnesota
  • The Children's Mercy Hospital
  • Dartmouth Hitchcock Medical Center
  • UBMD Pediatrics/ CF Center of Western New York
  • Columbia University Medical Center
  • SUNY Upstate Medical University
  • Wake Forest Baptist Health
  • Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
  • Children's Hospital of Pittsburgh of UPMC
  • Medical University of South Carolina (MUSC)
  • Sanford Children's Speciality Clinic
  • Austin Children's Chest Associates
  • Cook Children's Medical Center
  • Baylor College of Medicine
  • Children's Hospital of The King's Daughters
  • Seattle Children's Hospital
  • Children's Hospital of Wisconsin
  • Perth Children's Hospital
  • John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital
  • Lady Cilento Children's Hospital
  • The Children's Hospital at Westmead
  • Universitair Ziekenhuis Brussel - Campus Jette
  • Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
  • British Columbia's Children's Hospital
  • The Hospital for Sick Children
  • McGill University Health Centre, Glen Site, Montreal Children's Hospital
  • Juliane Marie Center, Rigshopitalet
  • Groupe Hospitaler Pellegrin, CHU De Bordeaux
  • Hopital Necker, Enfants Malades
  • Universitätsklinikum Essen
  • Clinic of J.W. Goethe University
  • Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin
  • Medizinische Hochschule Hannover
  • Universitaetsklinikum Jena, Mukoviszidose-Zentrum
  • Universitaetsklinkum Koeln, CF-Studienzentrum
  • Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin
  • Our Lady's Children's Hospital
  • University Hospital Limerick
  • Klinika Mukowiscydozy IMD Oddozial Chorob Pluc Szpzoz IM. Dzieci WarszaWY
  • Inselspital - Universitaetsspital Bern
  • Kinderspital Zuerich
  • Leeds General Infirmary
  • Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
  • Southampton General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TEZ/IVA

Arm Description

TEZ 50 mg once daily (qd)/IVA 75 mg every 12 hours (q12h) or TEZ 100 mg qd/IVA 150 mg q12h based on body weight for participants aged 6 through 11 years at enrollment and TEZ 100 mg qd/IVA 150 mg q12h for participants aged >=12 years at enrollment. Doses were adjusted upward for changes in body weight and/or age.

Outcomes

Primary Outcome Measures

Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary Outcome Measures

Part A: Absolute Change in Lung Clearance Index2.5 (LCI2.5) for 115/116 FAS (TEZ/IVA Group)
LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Part A: Absolute Change in LCI2.5 for 113B/116 LCI FAS
LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Part A: Absolute Change in Sweat Chloride for 115/116 FAS (TEZ/IVA Group)
Sweat samples were collected using an approved collection device.
Part A: Absolute Change in SwCl for 113B/116 FAS
Sweat samples were collected using an approved collection device.
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.
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.
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).
Part A: Absolute Change in BMI for 113B/116 FAS
BMI was defined as weight in kg divided by m^2.

Full Information

First Posted
May 15, 2018
Last Updated
October 4, 2023
Sponsor
Vertex Pharmaceuticals Incorporated
search

1. Study Identification

Unique Protocol Identification Number
NCT03537651
Brief Title
A Study to Evaluate the Safety and Efficacy of Long-term Treatment With TEZ/IVA in CF Subjects 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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 25, 2018 (Actual)
Primary Completion Date
October 28, 2020 (Actual)
Study Completion Date
July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
130 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TEZ/IVA
Arm Type
Experimental
Arm Description
TEZ 50 mg once daily (qd)/IVA 75 mg every 12 hours (q12h) or TEZ 100 mg qd/IVA 150 mg q12h based on body weight for participants aged 6 through 11 years at enrollment and TEZ 100 mg qd/IVA 150 mg q12h for participants aged >=12 years at enrollment. Doses were adjusted upward for changes in body weight and/or age.
Intervention Type
Drug
Intervention Name(s)
TEZ/IVA
Other Intervention Name(s)
VX-661/VX-770, tezacaftor/ivacaftor
Intervention Description
Fixed-dose combination tablet for oral administration.
Intervention Type
Drug
Intervention Name(s)
IVA
Other Intervention Name(s)
VX-770, ivacaftor
Intervention Description
Tablet for oral administration.
Primary Outcome Measure Information:
Title
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
Part A: Day 1 up to Week 100
Secondary Outcome Measure Information:
Title
Part A: Absolute Change in Lung Clearance Index2.5 (LCI2.5) for 115/116 FAS (TEZ/IVA Group)
Description
LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Time Frame
From Parent Study 115 Baseline at Week 96 (Study 116)
Title
Part A: Absolute Change in LCI2.5 for 113B/116 LCI FAS
Description
LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Time Frame
From Parent Study 113B Baseline at Week 96 (Study 116)
Title
Part A: Absolute Change in Sweat Chloride for 115/116 FAS (TEZ/IVA Group)
Description
Sweat samples were collected using an approved collection device.
Time Frame
From Parent Study 115 Baseline at Week 96 (Study 116)
Title
Part A: Absolute Change in SwCl for 113B/116 FAS
Description
Sweat samples were collected using an approved collection device.
Time Frame
From Parent Study 113B Baseline at Week 96 (Study 116)
Title
Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 115/116 FAS (TEZ/IVA Group)
Description
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.
Time Frame
From Parent Study 115 Baseline at Week 96 (Study 116)
Title
Part A: Absolute Change in CFQ-R Respiratory Domain Score for 113B/116 FAS
Description
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.
Time Frame
From Parent Study 113B Baseline at Week 96 (Study 116)
Title
Part A: Absolute Change in Body Mass Index (BMI) for 115/116 FAS (TEZ/IVA Group)
Description
BMI was defined as weight in kilograms (kg) divided by squared height in meters (m^2).
Time Frame
From Parent Study 115 Baseline at Week 96 (Study 116)
Title
Part A: Absolute Change in BMI for 113B/116 FAS
Description
BMI was defined as weight in kg divided by m^2.
Time Frame
From Parent Study 113B Baseline at Week 96 (Study 116)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Providence Alaska Medical Center
City
Anchorage
State/Province
Alaska
ZIP/Postal Code
99508
Country
United States
Facility Name
Arkansas Children's Hospital
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Nemours/ Alfred I. duPont Hospital for Children
City
Wilmington
State/Province
Delaware
ZIP/Postal Code
19803
Country
United States
Facility Name
Johns Hopkins All Children's Hospital Outpatient Care Center
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
Center for Advanced Pediatrics
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Facility Name
St. Luke's CF Center of Idaho
City
Boise
State/Province
Idaho
ZIP/Postal Code
83702
Country
United States
Facility Name
Riley Hospital for Children Indiana University Health
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Children's Hospital & Clinics of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
The Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Dartmouth Hitchcock Medical Center
City
Manchester
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
UBMD Pediatrics/ CF Center of Western New York
City
Buffalo
State/Province
New York
ZIP/Postal Code
14203
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
SUNY Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13202
Country
United States
Facility Name
Wake Forest Baptist Health
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Children's Hospital of Pittsburgh of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Medical University of South Carolina (MUSC)
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Sanford Children's Speciality Clinic
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57105
Country
United States
Facility Name
Austin Children's Chest Associates
City
Austin
State/Province
Texas
ZIP/Postal Code
78723
Country
United States
Facility Name
Cook Children's Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Children's Hospital of The King's Daughters
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Perth Children's Hospital
City
Nedlands
Country
Australia
Facility Name
John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital
City
New Lambton
Country
Australia
Facility Name
Lady Cilento Children's Hospital
City
South Brisbane
Country
Australia
Facility Name
The Children's Hospital at Westmead
City
Westmead
Country
Australia
Facility Name
Universitair Ziekenhuis Brussel - Campus Jette
City
Brussels
Country
Belgium
Facility Name
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
City
Leuven
Country
Belgium
Facility Name
British Columbia's Children's Hospital
City
Vancouver
State/Province
British Columbia
Country
Canada
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
McGill University Health Centre, Glen Site, Montreal Children's Hospital
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
Juliane Marie Center, Rigshopitalet
City
Copenhagen
Country
Denmark
Facility Name
Groupe Hospitaler Pellegrin, CHU De Bordeaux
City
Bordeaux cedex
Country
France
Facility Name
Hopital Necker, Enfants Malades
City
Paris Cedex 15
Country
France
Facility Name
Universitätsklinikum Essen
City
Essen
Country
Germany
Facility Name
Clinic of J.W. Goethe University
City
Frankfurt
Country
Germany
Facility Name
Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin
City
Giessen
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
Country
Germany
Facility Name
Universitaetsklinikum Jena, Mukoviszidose-Zentrum
City
Jena
Country
Germany
Facility Name
Universitaetsklinkum Koeln, CF-Studienzentrum
City
Koeln
Country
Germany
Facility Name
Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin
City
Tuebingen
Country
Germany
Facility Name
Our Lady's Children's Hospital
City
Dublin
Country
Ireland
Facility Name
University Hospital Limerick
City
Limerick
Country
Ireland
Facility Name
Klinika Mukowiscydozy IMD Oddozial Chorob Pluc Szpzoz IM. Dzieci WarszaWY
City
Lomianki
Country
Poland
Facility Name
Inselspital - Universitaetsspital Bern
City
Bern
Country
Switzerland
Facility Name
Kinderspital Zuerich
City
Zürich
Country
Switzerland
Facility Name
Leeds General Infirmary
City
Leeds
Country
United Kingdom
Facility Name
Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
City
London
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
35190292
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.
Results Reference
derived
PubMed Identifier
33331662
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs