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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04058353




Registration number
NCT04058353
Ethics application status
Date submitted
14/08/2019
Date registered
15/08/2019
Date last updated
15/05/2020

Titles & IDs
Public title
A Phase 3 Study of VX-445 Combination Therapy in Cystic Fibrosis (CF) Subjects Heterozygous for F508del and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)
Scientific title
A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)
Secondary ID [1] 0 0
2018-002835-76
Secondary ID [2] 0 0
VX18-445-104
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 - IVA
Treatment: Drugs - TEZ/IVA

Experimental: Triple Combination Arm - Subjects will receive ELX/TEZ/IVA TC in the morning and IVA as mono tablet in the evening.

Active Comparator: Control Arm - Subjects will receive either IVA as mono tablet OR TEZ/IVA as FDC in the morning and IVA as mono tablet in the evening.


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

Treatment: Drugs: IVA
150-mg tablet for oral administration

Treatment: Drugs: TEZ/IVA
FDC 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 percent predicted forced expiratory volume in 1 second (ppFEV1) for ELX/TEZ/IVA group
Timepoint [1] 0 0
From Baseline through Week 8
Secondary outcome [1] 0 0
Absolute change in sweat chloride (SwCl) for ELX/TEZ/IVA group
Timepoint [1] 0 0
From Baseline through Week 8
Secondary outcome [2] 0 0
Absolute change in ppFEV1 for ELX/TEZ/IVA group compared to the control group
Timepoint [2] 0 0
From Baseline through Week 8
Secondary outcome [3] 0 0
Absolute change in SwCl for ELX/TEZ/IVA group compared to the control group
Timepoint [3] 0 0
From Baseline through Week 8
Secondary outcome [4] 0 0
Absolute change from baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score for ELX/TEZ/IVA group
Timepoint [4] 0 0
From Baseline through Week 8
Secondary outcome [5] 0 0
Absolute change in CFQ-R respiratory domain score for ELX/TEZ/IVA group compared to the control group
Timepoint [5] 0 0
From Baseline through Week 8
Secondary outcome [6] 0 0
Safety and tolerability as assessed by number of subjects with adverse events (AEs) and serious adverse events (SAEs)
Timepoint [6] 0 0
From Baseline up to Week 12

Eligibility
Key inclusion criteria
Key

- Subject has a confirmed diagnosis of CF and is heterozygous for F508del and either a
gating or residual function mutation (F/G and F/RF genotypes)

- 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
Gender
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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [2] 0 0
Alfred Hospital - Melbourne, VIC
Recruitment hospital [3] 0 0
Perth Children's Hospital - Nedlands
Recruitment hospital [4] 0 0
The Royal Children's Hospital - Parkville, VIC
Recruitment hospital [5] 0 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [6] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [7] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
- Chermside
Recruitment postcode(s) [2] 0 0
- Melbourne, VIC
Recruitment postcode(s) [3] 0 0
- Nedlands
Recruitment postcode(s) [4] 0 0
- Parkville, VIC
Recruitment postcode(s) [5] 0 0
- South Brisbane
Recruitment postcode(s) [6] 0 0
- Westmead
Recruitment outside Australia
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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 heterozygous for F508del and a gating or residual function
mutation (F/G and F/RF genotypes).
Trial website
https://clinicaltrials.gov/show/NCT04058353
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
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Contact person for public queries
Name 0 0
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Contact person for scientific queries

Summary results
Other publications