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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02951182




Registration number
NCT02951182
Ethics application status
Date submitted
26/10/2016
Date registered
1/11/2016
Date last updated
28/08/2020

Titles & IDs
Public title
A Study Evaluating the Safety and Efficacy of VX-440 Combination Therapy in Subjects With Cystic Fibrosis
Scientific title
A Phase 2, Randomized, Double-blind, Controlled Study to Evaluate the Safety and Efficacy of VX-440 Combination Therapy in Subjects Aged 12 Years and Older With Cystic Fibrosis
Secondary ID [1] 0 0
2016-000454-36
Secondary ID [2] 0 0
VX15-440-101
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
Treatment: Drugs - IVA
Treatment: Drugs - VX-440
Treatment: Drugs - Matched Placebo

Placebo Comparator: Part 1: Placebo - Cohort 1A and 1B Combined - Participants received placebo matched to VX-440/TEZ/IVA as triple combination for 4 weeks.

Experimental: Part 1 Cohort 1A: Triple Combination (TC) - Participants received VX-440 200 milligram (mg) every 12 hours (q12h)/TEZ 100 mg once daily (qd)/IVA 150 mg q12h as triple combination for 4 weeks.

Experimental: Part 1 Cohort 1B: TC Low Dose - Participants received VX-440 200 mg q12h/TEZ 50 mg q12h/IVA 150 mg q12h as triple combination for 4 weeks.

Experimental: Part 1 Cohort 1B: TC High Dose - Participants received VX-440 600 mg q12h/TEZ 50 mg q12h/IVA 300 mg q12h as triple combination for 4 weeks.

Active Comparator: Part 2: TEZ/IVA - Following a 4-week run-in period on TEZ 100 mg qd/IVA150 mg q12h, participants received placebo matched to VX-440 and TEZ 50 mg q12h/IVA 300 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA150 mg q12h for 4 weeks in washout period.

Experimental: Part 2: TC-2 - Following a 4-week run-in period on TEZ 100 mg qd/IVA150 mg q12h, participants received VX-440 600 mg q12h/ TEZ 50 mg q12h/IVA 300 mg q12h for 4 weeks for 4 weeks in treatment period and TEZ 100 mg qd/IVA150 mg q12h for 4 weeks in washout period.


Treatment: Drugs: TEZ


Treatment: Drugs: IVA


Treatment: Drugs: VX-440


Treatment: Drugs: Matched Placebo


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 Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [1] 0 0
From first dose of Study Drug in the Treatment Period through Safety Follow-up Visit (Up to Day 57 for Part 1 and Day 85 for Part 2)
Primary outcome [2] 0 0
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) - FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Timepoint [2] 0 0
From Baseline through Day 29
Secondary outcome [1] 0 0
Absolute Change in Sweat Chloride Concentrations - Sweat samples were collected using an approved collection device.
Timepoint [1] 0 0
From Baseline through Day 29
Secondary outcome [2] 0 0
Relative Change in ppFEV1 - FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
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 - The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Timepoint [3] 0 0
From Baseline at Day 29
Secondary outcome [4] 0 0
Pre-dose Plasma Concentration (Ctrough) of VX-440, TEZ, M1-TEZ, IVA and M1-IVA
Timepoint [4] 0 0
Predose at Day 8, Day 15 and Day 29

Eligibility
Key inclusion criteria
- Willing and able to comply with scheduled visits, treatment plan, study restrictions,
laboratory tests, contraceptive guidelines, and other study procedures.

- To prevent pregnancy, female participants of childbearing potential and their male
partners will be required to use pre-specified, highly effective methods of
non-hormonal contraception. Male participants with female partners of childbearing
potential will be required to use a condom.

- Body weight =35 kg.

- Sweat chloride value =60 mmol/L from test results obtained during screening.

- Subjects must have an eligible CFTR genotype:

- Heterozygous for F508del and a minimal function (MF) mutation known or predicted
not to be responsive to TEZ and/or IVA.

- Homozygous for F508del

- Subjects must have an FEV1 =40% and =90% of predicted normal for age, sex, and height
at the Screening Visit

- Stable CF disease as judged by the investigator.

- Willing to remain on a stable CF medication regimen through the planned end of
treatment or, if applicable, the Safety Follow up Visit.
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of any comorbidity that, in the opinion of the investigator, might confound
the results of the study or pose an additional risk in administering study drug to the
subject.

- History of cirrhosis with portal hypertension.

- Risk factors for Torsade de Pointes

- History of hemolysis.

- Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.

- Clinically significant abnormal laboratory values at screening

- An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in
therapy for pulmonary disease within 28 days before the first dose of study drug.

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

- An acute illness not related to CF within 14 days before the first dose of study drug

- A standard digital ECG demonstrating QTc >450 msec at screening.

- History of solid organ or hematological transplantation.

- History or evidence of cataract or lens opacity determined to be clinically
significant by the ophthalmologist or optometrist based on the ophthalmologic
examination during the Screening Period.

- History of alcohol or drug abuse in the past year, including but not limited to,
cannabis, cocaine, and opiates, as deemed by the investigator.

- Ongoing or prior participation in an investigational drug study, with certain
exceptions. (e.g., ongoing participation in NCT02565914)

- Use of commercially available CFTR modulator (e.g., Kalydeco, Orkambi) within 14 days
before screening (applies only to the Heterozygous F508del/MF cohorts; does not apply
to the Homozygous F508del/F508del Cohort).

- Pregnant or nursing females: Females of childbearing potential must have a negative
pregnancy test at screening and Day 1.

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 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)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Prince Charles Hospital - Chermside
Recruitment hospital [3] 0 0
John Hunter Hospital & Hunter Medical Research Institute - New Lambton Heights
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Chermside
Recruitment postcode(s) [3] 0 0
- New Lambton Heights
Recruitment outside Australia
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United States of America
State/province [1] 0 0
Arizona
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United States of America
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California
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Colorado
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Florida
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Idaho
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Illinois
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Maryland
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Massachusetts
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United States of America
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Minnesota
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New York
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Ohio
Country [12] 0 0
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Oklahoma
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Pennsylvania
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South Dakota
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Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Virginia
Country [17] 0 0
United States of America
State/province [17] 0 0
Washington
Country [18] 0 0
Austria
State/province [18] 0 0
Innsbruck
Country [19] 0 0
Belgium
State/province [19] 0 0
Brussels
Country [20] 0 0
Belgium
State/province [20] 0 0
Leuven
Country [21] 0 0
Canada
State/province [21] 0 0
British Columbia
Country [22] 0 0
Canada
State/province [22] 0 0
Ontario
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Copenhagen
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Germany
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Jena
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Germany
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Koeln
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Germany
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Muenchen
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Italy
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Milano
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Spain
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Barcelona
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Spain
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Seville
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United Kingdom
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Birmingham
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United Kingdom
State/province [31] 0 0
London
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United Kingdom
State/province [32] 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 is a Phase 2, randomized, double-blind, placebo- and active-controlled, parallel group,
multicenter study to evaluate the safety, tolerability, and efficacy of VX-440 in dual and
triple combination with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with
cystic fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane
conductance regulator (CFTR) gene (F508del/F508del), or who are heterozygous for the F508del
mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ and/or IVA
therapy (F508del/MF).
Trial website
https://clinicaltrials.gov/show/NCT02951182
Trial related presentations / publications
Public notes

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

Summary results
Other publications