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

Phase 3

Completed

Conditions: Cystic Fibrosis

Interventions: Drug: TEZ/IVA
Drug: IVA

Registration Number: NCT03537651

Lead Sponsor: Vertex Pharmaceuticals Incorporated

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 130

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TEZ/IVA	IVA	Part A: Participants weighing less than (\<)40 kilograms (kg) at Day 1 received tezacaftor (TEZ) 50 milligrams (mg) once daily (qd)/ivacaftor (IVA) 75 mg every 12 hours (q12h) and the participants weighing greater than or equals to (\>=) 40 kg at Day 1 received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 96 weeks. Doses were adjusted upward for changes in body weight and/or age. Part B: Participants weighing \<30 kg at Day 1 received TEZ 50 mg qd/IVA 75 mg q12h and the participants weighing \>=30 kg at Day 1 received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period up to 192 weeks. Doses were adjusted upward for changes in body weight and/or age.
TEZ/IVA	TEZ/IVA	Part A: Participants weighing less than (\<)40 kilograms (kg) at Day 1 received tezacaftor (TEZ) 50 milligrams (mg) once daily (qd)/ivacaftor (IVA) 75 mg every 12 hours (q12h) and the participants weighing greater than or equals to (\>=) 40 kg at Day 1 received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 96 weeks. Doses were adjusted upward for changes in body weight and/or age. Part B: Participants weighing \<30 kg at Day 1 received TEZ 50 mg qd/IVA 75 mg q12h and the participants weighing \>=30 kg at Day 1 received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period up to 192 weeks. Doses were adjusted upward for changes in body weight and/or age.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 115/116 FAS (TEZ/IVA Group)	From Parent Study 115 Baseline at Week 96 (Study 116)	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)	From Parent Study 115 Baseline at Week 96 (Study 116)	BMI was defined as weight in kilograms (kg) divided by squared height in meters (m\^2).
Part A: Absolute Change in CFQ-R Respiratory Domain Score for 113B/116 FAS	From Parent Study 113B Baseline at Week 96 (Study 116)	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 BMI for 113B/116 FAS	From Parent Study 113B Baseline at Week 96 (Study 116)	BMI was defined as weight in kg divided by m\^2.
Part A: Absolute Change in Lung Clearance Index2.5 (LCI2.5) for 115/116 FAS (TEZ/IVA Group)	From Parent Study 115 Baseline at Week 96 (Study 116)	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.
Part A: Absolute Change in LCI2.5 for 113B/116 LCI FAS	From Parent Study 113B Baseline at Week 96 (Study 116)	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.
Part A: Absolute Change in Sweat Chloride (SwCl) for 115/116 FAS (TEZ/IVA Group)	From Parent Study 115 Baseline at Week 96 (Study 116)	Sweat samples were collected using an approved collection device.
Part A: Absolute Change in SwCl for 113B/116 FAS	From Parent Study 113B Baseline at Week 96 (Study 116)	Sweat samples were collected using an approved collection device.
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

Trial Locations

Locations (55): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Providence Alaska Medical Center
🇺🇸
Anchorage, Alaska, United States
Arkansas Children's Hospital
🇺🇸
Little Rock, Arkansas, United States
Children's Hospital Los Angeles
🇺🇸
Los Angeles, California, United States
Children's Hospital Colorado
🇺🇸
Aurora, Colorado, United States
Nemours/ Alfred I. duPont Hospital for Children
🇺🇸
Wilmington, Delaware, United States
Johns Hopkins All Children's Hospital Outpatient Care Center
🇺🇸
Saint Petersburg, Florida, United States
Center for Advanced Pediatrics
🇺🇸
Atlanta, Georgia, United States
St. Luke's CF Center of Idaho
🇺🇸
Boise, Idaho, United States
Riley Hospital for Children Indiana University Health
🇺🇸
Indianapolis, Indiana, United States
Scroll for more (45 remaining)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States