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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04105972




Registration number
NCT04105972
Ethics application status
Date submitted
24/09/2019
Date registered
26/09/2019
Date last updated
18/08/2021

Titles & IDs
Public title
A Study Evaluating the Efficacy and Safety of VX-445/Tezacaftor/Ivacaftor in Cystic Fibrosis Subjects, Homozygous for F508del
Scientific title
A Phase 3b, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-445/Tezacaftor/Ivacaftor in Cystic Fibrosis Subjects, Homozygous for F508del
Secondary ID [1] 0 0
2019-001735-31
Secondary ID [2] 0 0
VX18-445-109
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(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - ELX/TEZ/IVA
Treatment: Drugs - TEZ/IVA
Treatment: Drugs - IVA

Active comparator: TEZ/IVA - Following TEZ/IVA run-in period of 4 weeks, participants received TEZ 100 milligrams (mg) once daily (qd)/IVA 150 mg every 12 hours (q12h) in the treatment period for 24 weeks.

Experimental: ELX/TEZ/IVA - Following TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.


Treatment: Drugs: ELX/TEZ/IVA
FDC tablet for oral administration.

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

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

Outcomes
Primary outcome [1] 0 0
Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Timepoint [1] 0 0
From Baseline Through Week 24
Secondary outcome [1] 0 0
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Timepoint [1] 0 0
From Baseline Through Week 24
Secondary outcome [2] 0 0
Absolute Change in Sweat Chloride (SwCl)
Timepoint [2] 0 0
From Baseline Through Week 24
Secondary outcome [3] 0 0
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [3] 0 0
From Day 1 in the Treatment Period up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First (up to Week 28)

Eligibility
Key inclusion criteria
Key

* Homozygous for the F508del mutation (F/F)
* Forced expiratory volume in 1 second (FEV1) value =40% and =90% of predicted mean for age, sex, and height

Key
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Clinically significant cirrhosis with or without portal hypertension
* Lung infection with organisms associated with a more rapid decline in pulmonary status
* Solid organ or hematological transplantation

Other protocol defined Inclusion/Exclusion criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
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
3/10/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/07/2020
Sample size
Target
Accrual to date
Final
176
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [2] 0 0
Institute for Respiratory Health - Nedlands
Recruitment hospital [3] 0 0
Perth Children's Hospital - Nedlands
Recruitment hospital [4] 0 0
John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital - New Lambton
Recruitment hospital [5] 0 0
The Royal Children's Hospital - Parkville, VIC
Recruitment hospital [6] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 0 0
- Chermside
Recruitment postcode(s) [2] 0 0
- Nedlands
Recruitment postcode(s) [3] 0 0
- New Lambton
Recruitment postcode(s) [4] 0 0
- Parkville, VIC
Recruitment postcode(s) [5] 0 0
- South Brisbane
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Brussels
Country [2] 0 0
Belgium
State/province [2] 0 0
Edegem
Country [3] 0 0
Belgium
State/province [3] 0 0
Gent
Country [4] 0 0
Belgium
State/province [4] 0 0
Leuven
Country [5] 0 0
Germany
State/province [5] 0 0
Berlin
Country [6] 0 0
Germany
State/province [6] 0 0
Essen
Country [7] 0 0
Germany
State/province [7] 0 0
Frankfurt
Country [8] 0 0
Germany
State/province [8] 0 0
Jena
Country [9] 0 0
Germany
State/province [9] 0 0
Koeln
Country [10] 0 0
Germany
State/province [10] 0 0
Muenchen
Country [11] 0 0
Germany
State/province [11] 0 0
München
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Belfast
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Birmingham
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Bristol
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Cambridge
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Edinburgh
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Exeter
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Glasgow
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Leeds, West Yorkshire
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Leeds
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Liverpool
Country [22] 0 0
United Kingdom
State/province [22] 0 0
London
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Manchester
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Newcastle Upon Tyne
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Nottingham
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Penarth
Country [27] 0 0
United Kingdom
State/province [27] 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 will evaluate the efficacy, safety, and pharmacodynamics of elexacaftor (ELX, VX-445) in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous for F508del.
Trial website
https://clinicaltrials.gov/study/NCT04105972
Trial related presentations / publications
Sutharsan S, McKone EF, Downey DG, Duckers J, MacGregor G, Tullis E, Van Braeckel E, Wainwright CE, Watson D, Ahluwalia N, Bruinsma BG, Harris C, Lam AP, Lou Y, Moskowitz SM, Tian S, Yuan J, Waltz D, Mall MA; VX18-445-109 study group. Efficacy and safety of elexacaftor plus tezacaftor plus ivacaftor versus tezacaftor plus ivacaftor in people with cystic fibrosis homozygous for F508del-CFTR: a 24-week, multicentre, randomised, double-blind, active-controlled, phase 3b trial. Lancet Respir Med. 2022 Mar;10(3):267-277. doi: 10.1016/S2213-2600(21)00454-9. Epub 2021 Dec 20.
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/NCT04105972