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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03227471




Registration number
NCT03227471
Ethics application status
Date submitted
18/07/2017
Date registered
24/07/2017
Date last updated
19/11/2019

Titles & IDs
Public title
A Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis
Scientific title
A Phase 1/2 Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis
Secondary ID [1] 0 0
2017-000797-11
Secondary ID [2] 0 0
VX16-445-001
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 - IVA
Treatment: Drugs - TEZ/IVA
Treatment: Drugs - VX-445
Treatment: Drugs - Matched Placebo
Treatment: Drugs - TEZ
Treatment: Drugs - VX-561

Experimental: Part A: VX-445 in Healthy Subjects (HS) - Part A includes single dose escalation.

Placebo Comparator: Part A: Placebo -

Experimental: Part B: VX-445 in HS - Part B includes multiple-dose escalation.

Placebo Comparator: Part B: Placebo -

Experimental: Part C: VX-445 in Triple Combination (TC) with TEZ/IVA in HS - Multiple-dose escalation of VX-445 in TC with TEZ/IVA

Placebo Comparator: Part C: Placebo -

Experimental: Part D1: F/MF genotypes TC - Subjects will receive 100 mg VX-445 qd in TC with TEZ and IVA for 4 weeks.

Placebo Comparator: Part D1: Placebo - Subjects will receive placebo for 4 weeks.

Experimental: Part D2: F/MF genotypes TC-High - Subjects will receive VX-445 in TC with TEZ and IVA for 4 weeks.

Experimental: Part D2: F/MF genotypes TC-Mid - Subjects will receive VX-445 in TC with TEZ and IVA for 4 weeks.

Experimental: Part D2: F/MF genotypes TC-Low - Subjects will receive VX-445 in TC with TEZ and IVA for 4 weeks.

Placebo Comparator: Part D2: Placebo -

Experimental: Part E: F/F genotype - TC - Subjects will receive VX-445 in TC with TEZ and IVA for 4 weeks

Active Comparator: Part E: TEZ/IVA - Subjects will receive TEZ and IVA for 4 weeks.

Experimental: Part F: F/MF genotypes - TC - Subjects will receive VX-445 in TC with TEZ and VX-561 for 4 weeks.

Experimental: Part F: Placebo -


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

Treatment: Drugs: TEZ/IVA
100-mg TEZ / 150-mg IVA fixed dose combination (FDC) tablet for oral administration.

Treatment: Drugs: VX-445
VX-445 tablet for oral administration.

Treatment: Drugs: Matched Placebo
Matched placebo.

Treatment: Drugs: TEZ
50-mg tablet for oral administration.

Treatment: Drugs: VX-561
50-mg tablet for oral administration.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability as assessed by number of subjects with adverse events (AEs) and serious adverse events (SAEs) - Number of subjects with AEs and SAEs will be reported.
Timepoint [1] 0 0
from baseline through safety follow-up (up to 10 days after last dose for Part A, B, and C)
Primary outcome [2] 0 0
Safety and tolerability as assessed by number of subjects with adverse events (AEs) and serious adverse events (SAEs) - Number of subjects with AEs and SAEs will be reported.
Timepoint [2] 0 0
from baseline through safety follow-up (up to 35 days after last dose for Parts D, E, and F).
Primary outcome [3] 0 0
Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) [Parts D, E, and F only] - Absolute change in ppFEV1 will be reported.
Timepoint [3] 0 0
from baseline through Day 29
Secondary outcome [1] 0 0
Absolute change in sweat chloride concentrations [Parts C, D, E, and F only] - Absolute change in sweat chloride concentrations will be reported.
Timepoint [1] 0 0
from baseline through Day 29
Secondary outcome [2] 0 0
Relative change in ppFEV1 [Parts D, E, and F only] - Relative change in ppFEV1 will be reported.
Timepoint [2] 0 0
from baseline through Day 29
Secondary outcome [3] 0 0
Absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score [Parts D, E, and F only] - The absolute change in CFQ-R respiratory domain score will be reported.
Timepoint [3] 0 0
from baseline through Day 29
Secondary outcome [4] 0 0
Maximum observed concentration (Cmax) of VX-445,TEZ and metabolites (M1-TEZ and M2-TEZ), IVA and metabolites (M1-IVA and M6-IVA) and VX-561 - Maximum plasma concentration [Cmax] will be reported.
Timepoint [4] 0 0
from Day 1 through Day 43
Secondary outcome [5] 0 0
Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-445, TEZ and metabolites (M1-TEZ and M2-TEZ), IVA and metabolites (M1-IVA and M6-IVA) and VX-561 - Area under the concentration versus time curve during a dosing interval (AUCtau) will be reported.
Timepoint [5] 0 0
from Day 1 through Day 43
Secondary outcome [6] 0 0
Observed pre-dose concentration (Ctrough) of VX-445, TEZ and metabolites (M1-TEZ and M2-TEZ), IVA and metabolites (M1-IVA and M6-IVA) and VX-561 - Trough plasma concentration [Ctrough] will be reported.
Timepoint [6] 0 0
from Day 1 through Day 43

Eligibility
Key inclusion criteria
Key

Parts A, B, and C:

- Female subjects must be of non-childbearing potential.

- Between the ages of 18 and 55 years, inclusive.

- Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, and a total body weight >50 kg

Parts D, E, and F:

- Body weight =35 kg.

- Subjects must have an eligible CFTR genotype:

- Parts D and F: Heterozygous for F508del and an MF mutation (F/MF)

- Part E: Homozygous for F508del (F/F)

- FEV1 value =40% and =90% of predicted mean for age, sex, and height.

Key
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Parts A, B, and C:

- Any condition possibly affecting drug absorption.

- History of febrile illness within 14 days before the first study drug dose.

- Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Parts D, E, and F:

- History of clinically significant cirrhosis with or without portal hypertension.

- Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

- Lung infection with organisms associated with a more rapid decline in pulmonary
status.

- History of 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 1/Phase 2
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)
VIC
Recruitment hospital [1] 0 0
Monash Medical Center - Clayton
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [3] 0 0
The Royal Children's Hospital Melbourne - Parkville
Recruitment hospital [4] 0 0
Mater Adult Hospital - Brisbane
Recruitment hospital [5] 0 0
Royal Prince Alfred Hospital - Sydney
Recruitment hospital [6] 0 0
Westmead Hospital - Sydney
Recruitment postcode(s) [1] 0 0
- Clayton
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Parkville
Recruitment postcode(s) [4] 0 0
- Brisbane
Recruitment postcode(s) [5] 0 0
- Sydney
Recruitment outside Australia
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United States of America
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Arizona
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Arkansas
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California
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Colorado
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Florida
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Georgia
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Illinois
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Indiana
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Kansas
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United States of America
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Louisiana
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Michigan
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Minnesota
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New Jersey
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New Mexico
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Ohio
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Texas
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Vermont
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Virginia
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Wisconsin
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Belgium
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Edegem
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Belgium
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Gent
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Netherlands
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Amsterdam
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Netherlands
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Den Haag
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Netherlands
State/province [24] 0 0
Nijmegen
Country [25] 0 0
Netherlands
State/province [25] 0 0
Rotterdam

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a first-in-human and proof-of-concept study of VX-445. The study includes 6 parts.
Parts A, B, and C will be conducted in healthy subjects. Parts D, E, and F will be conducted
in subjects with Cystic Fibrosis (CF) who are homozygous for the F508del mutation of the CF
transmembrane conductance regulator (CFTR) gene (F/F genotype), or who are heterozygous for
the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ,
IVA, or TEZ/IVA (F/MF genotypes).
Trial website
https://clinicaltrials.gov/show/NCT03227471
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
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications