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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02875366




Registration number
NCT02875366
Ethics application status
Date submitted
15/08/2016
Date registered
23/08/2016
Date last updated
17/06/2019

Titles & IDs
Public title
A Study of the Effects of Lumacaftor/Ivacaftor (LUM/IVA) on Exercise Tolerance in Subjects With Cystic Fibrosis (CF), Homozygous for the F508del-CFTR Mutation
Scientific title
A Phase 4, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design Study of the Effect of Lumacaftor/Ivacaftor Combination Therapy on Exercise Tolerance in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
Secondary ID [1] 0 0
2016-000066-34
Secondary ID [2] 0 0
VX15-809-112
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 - LUM/IVA
Treatment: Drugs - Placebo

Placebo Comparator: Placebo - Placebo matched to LUM/IVA fixed-dose combination tablet orally every 12 hours (q12h) for 24 weeks.

Experimental: LUM/IVA - LUM 400 milligram (mg)/IVA 250 mg fixed-dose combination tablet orally q12h for 24 weeks.


Treatment: Drugs: LUM/IVA


Treatment: Drugs: Placebo


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

Outcomes
Primary outcome [1] 0 0
Relative (Percent) Change From Baseline in Maximal Oxygen Consumption (VO2max) During Cardiopulmonary Exercise Testing (CPET) at Week 24 - CPET was used to assess change in exercise tolerance, as measured by VO2max.
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [1] 0 0
Relative (Percent) Change From Baseline in Exercise Duration During CPET at Week 24 - Exercise duration is defined as the time at the termination of CPET exercise minus the corresponding time when CPET starts for each CPET exercise.
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [2] 0 0
Absolute Change From Baseline in Exercise Duration During CPET at Week 24 - Exercise duration is defined as the time at the termination of CPET exercise minus the corresponding time when CPET starts for each CPET exercise.
Timepoint [2] 0 0
Baseline, Week 24
Secondary outcome [3] 0 0
Absolute Change From Baseline in VO2max During CPET at Week 24 - CPET was used to assess change in exercise tolerance, as measured by VO2max.
Timepoint [3] 0 0
Baseline, Week 24
Secondary outcome [4] 0 0
Absolute Change From Baseline in Oxygen Consumption (VO2) at Anaerobic Threshold at Week 24 - Anaerobic threshold was defined as the exercise intensity at which lactate starts to accumulate.
Timepoint [4] 0 0
Baseline, Week 24
Secondary outcome [5] 0 0
Relative (Percent) Change From Baseline in VO2 at Anaerobic Threshold at Week 24 - Anaerobic threshold was defined as the exercise intensity at which lactate starts to accumulate.
Timepoint [5] 0 0
Baseline, Week 24
Secondary outcome [6] 0 0
Absolute Change From Baseline in Functional VO2 Gain at Week 24
Timepoint [6] 0 0
Baseline, Week 24
Secondary outcome [7] 0 0
Relative (Percent) Change From Baseline in Functional VO2 Gain at Week 24
Timepoint [7] 0 0
Baseline, Week 24
Secondary outcome [8] 0 0
Absolute Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24
Timepoint [8] 0 0
Baseline, Week 24
Secondary outcome [9] 0 0
Relative (Percent) Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24
Timepoint [9] 0 0
Baseline, Week 24
Secondary outcome [10] 0 0
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24 - FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Timepoint [10] 0 0
Baseline, Week 24
Secondary outcome [11] 0 0
Relative (Percent) Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24 - FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Timepoint [11] 0 0
Baseline, Week 24
Secondary outcome [12] 0 0
Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 - BMI was defined as weight in kilograms (kg) divided by height in square meter (m^2).
Timepoint [12] 0 0
Baseline, Week 24
Secondary outcome [13] 0 0
Relative (Percent) Change From Baseline in BMI at Week 24 - BMI was defined as weight in kg divided by height in m^2.
Timepoint [13] 0 0
Baseline, Week 24
Secondary outcome [14] 0 0
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24 - The CFQ-R assessed respiratory symptoms on a scale with scores ranging from 0 to 100; where higher scores indicated fewer symptoms and better health-related quality of life.
Timepoint [14] 0 0
Baseline, Week 24
Secondary outcome [15] 0 0
Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8) - The PHQ-8 is an eight item self-reported measure of depression. Each item is rated on a scale ranging from 0 (not at all) to 3 (nearly every day). Total score is the sum of individual eight items and ranges from 0 to 24, with higher scores indicating more severe depression symptoms. Total score of 0 to 5 indicates none to minimal depression, 6 to 10 indicates mild depression, 11 to 15 indicates moderate depression, 16 to 20 indicates moderately severe depression and 21 to 24 indicates severe depression.
Timepoint [15] 0 0
Baseline, Week 24
Secondary outcome [16] 0 0
Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores - The GAD-7 is a seven item, self-reported measurement of GAD severity. Each item is rated on a scale ranging from 0 (not at all) to 3 (nearly every day). Total score is the sum of individual seven items and ranges from 0 to 21, with higher scores indicating more severe anxiety symptoms. Total score of 0 to 5 indicates none to minimal anxiety, 6 to 10 indicates mild anxiety, 11 to 15 indicates moderate anxiety, 16 to 21 indicates severe anxiety.
Timepoint [16] 0 0
Baseline, Week 24
Secondary outcome [17] 0 0
Absolute Change From Baseline in Daily Physical Activity Counts as Determined by Actigraphy at Week 24 - Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily physical activity counts.
Timepoint [17] 0 0
Baseline, Week 24
Secondary outcome [18] 0 0
Relative (Percent) Change From Baseline in Physical Activity as Determined by Actigraphy at Week 24 - Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily physical activities.
Timepoint [18] 0 0
Baseline, Week 24
Secondary outcome [19] 0 0
Absolute Change From Baseline in Duration of Sleep Time at Week 24 - Participants were provided with a wrist-worn actigraphy device which continuously collected data about sleep duration and quality.
Timepoint [19] 0 0
Baseline, Week 24
Secondary outcome [20] 0 0
Relative (Percent) Change From Baseline in Duration of Sleep Time at Week 24 - Participants were provided with a wrist-worn actigraphy device which continuously collected data about sleep duration and quality.
Timepoint [20] 0 0
Baseline, Week 24
Secondary outcome [21] 0 0
Absolute Change From Baseline in Time Above Sedentary Duration at Week 24 - Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily activities and sleep duration and quality.
Timepoint [21] 0 0
Baseline, Week 24
Secondary outcome [22] 0 0
Relative (Percent) Change From Baseline in Time Above Sedentary Duration at Week 24 - Participants were provided with a wrist-worn actigraphy device which continuously collected data about daily activities and sleep duration and quality.
Timepoint [22] 0 0
Baseline, Week 24
Secondary outcome [23] 0 0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [23] 0 0
Day 1 up to Week 28

Eligibility
Key inclusion criteria
- Homozygous for the F508del-CFTR mutation

- Confirmed diagnosis of CF defined as a sweat chloride value =60 mmol/L by quantitative
pilocarpine iontophoresis

- Stable CF disease as judged by the investigator

- Forced expiratory volume in 1 second (FEV1) at least 40% and not greater than 90% of
predicted
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 might confound the results of the study, interfere
with the use of cardiopulmonary exercise tests (CPETs) as an assessment, or pose an
additional risk in administering study drug to the subject

- Any previous exposure to LUM or IVA

- History of cardiac arrhythmia, ischemic heart disease, congestive heart failure, or
other clinically significant cardiac condition, or medical condition requiring chronic
use of a beta blocker, non-dihydropyridine calcium channel blocker, or other cardiac
medication known to affect exercise tolerance

- History of solid organ or hematological transplantation

- For subjects under 18 years of age at Screening, except those who have had bilateral
lens removal, selected findings on a screening ophthalmologic examination will be
exclusionary

- Using or expected to require any concomitant medication that is prohibited in this
study

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

- Participation in an investigational drug study within 30 days before the Screening
Visit

- Pregnant or nursing females; males with a female partner who is pregnant or nursing

- Colonization with organisms associated with a more rapid decline in pulmonary status

Study design
Purpose of the study
Other
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 analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
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
- Melbourne
Recruitment hospital [2] 0 0
- Parkville
Recruitment hospital [3] 0 0
- Adelaide
Recruitment hospital [4] 0 0
- Camperdown
Recruitment hospital [5] 0 0
- Clayton
Recruitment hospital [6] 0 0
- Nedlands
Recruitment hospital [7] 0 0
- New Lambton Heights
Recruitment hospital [8] 0 0
- Randwick
Recruitment hospital [9] 0 0
- South Brisbane
Recruitment hospital [10] 0 0
- Subiaco
Recruitment hospital [11] 0 0
- Westmead
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment postcode(s) [2] 0 0
- Parkville
Recruitment postcode(s) [3] 0 0
- Adelaide
Recruitment postcode(s) [4] 0 0
- Camperdown
Recruitment postcode(s) [5] 0 0
- Clayton
Recruitment postcode(s) [6] 0 0
- Nedlands
Recruitment postcode(s) [7] 0 0
- New Lambton Heights
Recruitment postcode(s) [8] 0 0
- Randwick
Recruitment postcode(s) [9] 0 0
- South Brisbane
Recruitment postcode(s) [10] 0 0
- Subiaco
Recruitment postcode(s) [11] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
United Kingdom
State/province [1] 0 0
Edinburgh

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 4, randomized, double-blind, placebo-controlled, parallel-group study in
subjects aged 12 years and older with CF who are homozygous for the F508del-CFTR mutation.
This study is designed to evaluate the effect of LUM/IVA on exercise tolerance in subjects
with CF, homozygous for the F508del-CFTR mutation.
Trial website
https://clinicaltrials.gov/show/NCT02875366
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