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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03537651




Registration number
NCT03537651
Ethics application status
Date submitted
15/05/2018
Date registered
25/05/2018
Date last updated
19/04/2024

Titles & IDs
Public title
A Study to Evaluate the Safety and Efficacy of Long-term Treatment With TEZ/IVA in CF Participants With an F508del CFTR Mutation
Scientific 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
Secondary ID [1] 0 0
2017-002968-40
Secondary ID [2] 0 0
VX17-661-116
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TEZ/IVA
Treatment: Drugs - IVA

Experimental: 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.


Treatment: Drugs: TEZ/IVA
Fixed-dose combination tablet for oral administration.

Treatment: Drugs: IVA
Tablet for oral administration.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [1] 0 0
Day 1 up to Week 100
Secondary outcome [1] 0 0
Part A: Absolute Change in Lung Clearance Index2.5 (LCI2.5) for 115/116 FAS (TEZ/IVA Group)
Timepoint [1] 0 0
From Parent Study 115 Baseline at Week 96 (Study 116)
Secondary outcome [2] 0 0
Part A: Absolute Change in LCI2.5 for 113B/116 LCI FAS
Timepoint [2] 0 0
From Parent Study 113B Baseline at Week 96 (Study 116)
Secondary outcome [3] 0 0
Part A: Absolute Change in Sweat Chloride (SwCl) for 115/116 FAS (TEZ/IVA Group)
Timepoint [3] 0 0
From Parent Study 115 Baseline at Week 96 (Study 116)
Secondary outcome [4] 0 0
Part A: Absolute Change in SwCl for 113B/116 FAS
Timepoint [4] 0 0
From Parent Study 113B Baseline at Week 96 (Study 116)
Secondary outcome [5] 0 0
Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 115/116 FAS (TEZ/IVA Group)
Timepoint [5] 0 0
From Parent Study 115 Baseline at Week 96 (Study 116)
Secondary outcome [6] 0 0
Part A: Absolute Change in CFQ-R Respiratory Domain Score for 113B/116 FAS
Timepoint [6] 0 0
From Parent Study 113B Baseline at Week 96 (Study 116)
Secondary outcome [7] 0 0
Part A: Absolute Change in Body Mass Index (BMI) for 115/116 FAS (TEZ/IVA Group)
Timepoint [7] 0 0
From Parent Study 115 Baseline at Week 96 (Study 116)
Secondary outcome [8] 0 0
Part A: Absolute Change in BMI for 113B/116 FAS
Timepoint [8] 0 0
From Parent Study 113B Baseline at Week 96 (Study 116)
Secondary outcome [9] 0 0
Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [9] 0 0
Day 1 up to Week 192

Eligibility
Key inclusion criteria
* Completed the Week 24 Visit in Study 113 Part B or the Week 8 Visit in Study 115
* Eligible CFTR Mutation
Minimum age
6 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/04/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/09/2023
Sample size
Target
Accrual to date
Final
130
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Perth Children's Hospital - Nedlands
Recruitment hospital [2] 0 0
John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital - New Lambton
Recruitment hospital [3] 0 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment hospital [4] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
- Nedlands
Recruitment postcode(s) [2] 0 0
- New Lambton
Recruitment postcode(s) [3] 0 0
- South Brisbane
Recruitment postcode(s) [4] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
Alaska
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
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United States of America
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Delaware
Country [7] 0 0
United States of America
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Florida
Country [8] 0 0
United States of America
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Georgia
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United States of America
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Idaho
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Indiana
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Massachusetts
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Minnesota
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Missouri
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New Hampshire
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New York
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North Carolina
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Ohio
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Pennsylvania
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South Carolina
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South Dakota
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Texas
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Virginia
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Washington
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United States of America
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Wisconsin
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Belgium
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Brussels
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Belgium
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Leuven
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Canada
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British Columbia
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Canada
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Ontario
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Canada
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Quebec
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Denmark
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Copenhagen
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France
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Bordeaux cedex
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France
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Paris Cedex 15
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Germany
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Essen
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Germany
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Frankfurt
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Germany
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Giessen
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Germany
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Hannover
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Germany
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Jena
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Germany
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Koeln
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Tuebingen
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Limerick
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Bern
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Switzerland
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Zürich
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United Kingdom
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Leeds
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United Kingdom
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London
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United Kingdom
State/province [47] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Vertex Pharmaceuticals Incorporated
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03537651
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03537651