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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03525444




Registration number
NCT03525444
Ethics application status
Date submitted
2/05/2018
Date registered
15/05/2018
Date last updated
27/05/2019

Titles & IDs
Public title
A Phase 3 Study of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
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 Minimal Function Mutation (F/MF)
Secondary ID [1] 0 0
2018-000183-28
Secondary ID [2] 0 0
VX17-445-102
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
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
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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - VX-445
Treatment: Drugs - TEZ
Treatment: Drugs - IVA
Treatment: Drugs - Matched Placebos

Experimental: Triple Combination - Subjects will receive 200 mg VX-445/ 100 mg TEZ/ 150 mg IVA as FDC tablets in the morning and 150 mg IVA as mono tablet in the evening

Placebo Comparator: Placebo -


Treatment: Drugs: VX-445
Fixed dose combination (FDC) tablet (VX-445/TEZ/IVA)

Treatment: Drugs: TEZ
FDC tablet (VX-445/TEZ/IVA)

Treatment: Drugs: IVA
FDC tablet (VX-445/TEZ/IVA)

Treatment: Drugs: Matched Placebos
Placebo will be used as a comparator.

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)
Timepoint [1] 0 0
from baseline at Week 4
Secondary outcome [1] 0 0
Absolute change in ppFEV1
Timepoint [1] 0 0
from baseline through Week 24
Secondary outcome [2] 0 0
Number of pulmonary exacerbations (PEx)
Timepoint [2] 0 0
from baseline through Week 24
Secondary outcome [3] 0 0
Absolute change in body mass index (BMI)
Timepoint [3] 0 0
from baseline at Week 24
Secondary outcome [4] 0 0
Absolute change in sweat chloride (SwCl)
Timepoint [4] 0 0
from baseline at Week 4 and through Week 24
Secondary outcome [5] 0 0
Absolute change in Cystic Fibrosis Questionnaire Revised (CFQ-R) respiratory domain score
Timepoint [5] 0 0
from baseline at Week 4 and through Week 24
Secondary outcome [6] 0 0
Time-to-first PEx
Timepoint [6] 0 0
through Week 24
Secondary outcome [7] 0 0
Absolute change in BMI z-score
Timepoint [7] 0 0
from baseline at Week 24
Secondary outcome [8] 0 0
Absolute change in body weight
Timepoint [8] 0 0
from baseline at Week 24
Secondary outcome [9] 0 0
Safety and tolerability as assessed by number of subjects with adverse events (AEs) and serious adverse events (SAEs)
Timepoint [9] 0 0
from baseline through 4-week safety follow-up (up to 28 weeks)
Secondary outcome [10] 0 0
Observed pre-dose concentration (Ctrough) of VX-445, TEZ, M1-TEZ, and IVA
Timepoint [10] 0 0
from Day 1 through Week 16

Eligibility
Key inclusion criteria
Key

- Heterozygous for the F508del mutation (F/MF)

- 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
Completed
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
Women & Children's Hospital - North Adelaide
Recruitment hospital [2] 0 0
The Royal Children's Hospital - Parkville
Recruitment hospital [3] 0 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [4] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [5] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
- North Adelaide
Recruitment postcode(s) [2] 0 0
- Parkville
Recruitment postcode(s) [3] 0 0
- South Brisbane
Recruitment postcode(s) [4] 0 0
- Westmead
Recruitment outside Australia
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Firenze
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Genova
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Messina
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Potenza
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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 of 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 minimal function mutation (F/MF subjects).
Trial website
https://clinicaltrials.gov/show/NCT03525444
Trial related presentations / publications
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
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Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications