Cystic FibrosisPhase 4NCT02875366
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
A Phase 4 study testing LUM/IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 12 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- LUM/IVA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 12 sitesin 2 countries
- Study dates
- Sep 2016to Oct 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
Australia11 sites
Study site
Adelaide
Study site
Camperdown
Study site
Clayton
Study site
Melbourne, Victoria
Study site
Nedlands
Study site
New Lambton Heights
Study site
Parkville, Victoria
Study site
Randwick
Study site
South Brisbane
Study site
Subiaco
Study site
Westmead
About this study
Official 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
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.
- Conditions
- Cystic Fibrosis
- Being tested
- LUM/IVA, Placebo
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LUM/IVADrug
Also called Lumacaftor/Ivacaftor
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo matched to LUM/IVA fixed-dose combination tablet orally every 12 hours (q12h) for 24 weeks. Receives: Drug: Placebo |
| LUM/IVA | Experimental | LUM 400 milligram (mg)/IVA 250 mg fixed-dose combination tablet orally q12h for 24 weeks. Receives: Drug: LUM/IVA |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Week 24
Secondary outcomes (23)
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.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 24
Absolute Change From Baseline in VO2max During CPET at Week 24
CPET was used to assess change in exercise tolerance, as measured by VO2max.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 24
Absolute Change From Baseline in Functional VO2 Gain at Week 24
Measured: Baseline, Week 24
Relative (Percent) Change From Baseline in Functional VO2 Gain at Week 24
Measured: Baseline, Week 24
Absolute Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24
Measured: Baseline, Week 24
Relative (Percent) Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 24
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).
Measured: Baseline, Week 24
Relative (Percent) Change From Baseline in BMI at Week 24
BMI was defined as weight in kg divided by height in m^2.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 24
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.
Measured: Baseline, Week 24
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: Day 1 up to Week 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2016 (estimated)
- Study startSep 2016
- Primary completionSep 2017
- Study completionOct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Vertex Pharmaceuticals IncorporatedThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vertex Pharmaceuticals Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02875366
- Sponsor's protocol ID
- VX15-809-112
- Other IDs
- 2016-000066-34, 2016
- Status last verified
- Mar 2019
- First submitted
- 15 Aug 2016
- Last updated
- 17 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Wilson J, You X, Ellis M, Urquhart DS, Jha L, Duncan M, Tian S, Harris RA, Kotsimbos T, Keating D. VO2max as an exercise tolerance endpoint in people with cystic fibrosis: Lessons from a lumacaftor/ivacaftor trial. J Cyst Fibros. 2021 May;20(3):499-505. doi: 10.1016/j.jcf.2020.12.006. Epub 2020 Dec 24.
PubMed 33358691
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02875366
- Acronym / sponsor ID
- VX15-809-112
- Conditions
- Cystic Fibrosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- Sep 2016 (actual)
- Primary completion
- Sep 2017 (actual)
- Study completion
- Oct 2017 (actual)
- First posted
- 23 Aug 2016 (estimated)
- Results
- Posted 17 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo matched to LUM/IVA fixed-dose combination tablet orally every 12 hours (q12h) for 24 weeks. |
| LUM/IVA | Experimental | Drug: LUM/IVALUM 400 milligram (mg)/IVA 250 mg fixed-dose combination tablet orally q12h for 24 weeks. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LUM/IVAAlso: Lumacaftor/Ivacaftor | Drug | LUM/IVA |
| Placebo | Drug | Placebo |
Primary outcome
Relative (Percent) Change From Baseline in Maximal Oxygen Consumption (VO2max) During Cardiopulmonary Exercise Testing (CPET) at Week 24
Time frame: Baseline, Week 24
CPET was used to assess change in exercise tolerance, as measured by VO2max.
23 secondary outcomes
Relative (Percent) Change From Baseline in Exercise Duration During CPET at Week 24
Time frame: Baseline, Week 24
Absolute Change From Baseline in Exercise Duration During CPET at Week 24
Time frame: Baseline, Week 24
Absolute Change From Baseline in VO2max During CPET at Week 24
Time frame: Baseline, Week 24
Absolute Change From Baseline in Oxygen Consumption (VO2) at Anaerobic Threshold at Week 24
Time frame: Baseline, Week 24
Relative (Percent) Change From Baseline in VO2 at Anaerobic Threshold at Week 24
Time frame: Baseline, Week 24
Absolute Change From Baseline in Functional VO2 Gain at Week 24
Time frame: Baseline, Week 24
Relative (Percent) Change From Baseline in Functional VO2 Gain at Week 24
Time frame: Baseline, Week 24
Absolute Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24
Time frame: Baseline, Week 24
Relative (Percent) Change From Baseline in Pulmonary Ventilation (VE) Versus Carbon Dioxide Production (VCO2) Slope at Week 24
Time frame: Baseline, Week 24
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24
Time frame: Baseline, Week 24
Relative (Percent) Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24
Time frame: Baseline, Week 24
Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
Time frame: Baseline, Week 24
Relative (Percent) Change From Baseline in BMI at Week 24
Time frame: Baseline, Week 24
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24
Time frame: Baseline, Week 24
Number of Participants in Each Severity Category of Patient Health Questionnaire (PHQ-8)
Time frame: Baseline, Week 24
Number of Participants in Each Severity Category of Generalized Anxiety Disorder (GAD-7) Scores
Time frame: Baseline, Week 24
Absolute Change From Baseline in Daily Physical Activity Counts as Determined by Actigraphy at Week 24
Time frame: Baseline, Week 24
Relative (Percent) Change From Baseline in Physical Activity as Determined by Actigraphy at Week 24
Time frame: Baseline, Week 24
Absolute Change From Baseline in Duration of Sleep Time at Week 24
Time frame: Baseline, Week 24
Relative (Percent) Change From Baseline in Duration of Sleep Time at Week 24
Time frame: Baseline, Week 24
Absolute Change From Baseline in Time Above Sedentary Duration at Week 24
Time frame: Baseline, Week 24
Relative (Percent) Change From Baseline in Time Above Sedentary Duration at Week 24
Time frame: Baseline, Week 24
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Week 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33358691Wilson J, You X, Ellis M, Urquhart DS, Jha L, Duncan M, Tian S, Harris RA, Kotsimbos T, Keating D. VO2max as an exercise tolerance endpoint in people with cystic fibrosis: Lessons from a lumacaftor/ivacaftor trial. J Cyst Fibros. 2021 May;20(3):499-505. doi: 10.1016/j.jcf.2020.12.006. Epub 2020 Dec 24.
Related trials for Cystic Fibrosis
RecruitingPhase 2
A Study of 24 to 52 Weeks Treatment to Evaluate The Efficacy And Safety of Galvokimig in Adult Study Participants With Non-Cystic Fibrosis Bronchiectasis
Non-cystic Fibrosis Bronchiectasis
Active, not recruitingObservational study
CFTR Modulator Effects on Bone and Muscle in Adults With Cystic Fibrosis
Cystic Fibrosis, Bone Loss
RecruitingObservational study
Natural History of Bronchiectasis
Bronchiectasis, Cystic Fibrosis
RecruitingObservational study
Role of Genetic Factors in the Development of Lung Disease
Cystic Fibrosis, Pulmonary Fibrosis
RecruitingPhase 2
Early Study on Tamoxifen Safety/Tolerability in Cystic Fibrosis Patients Unable to Use CFTR Modulators.
Cystic Fibrosis - Complete
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing LUM/IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Australia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relative (Percent) Change From Baseline in Maximal Oxygen Consumption (VO2max) During Cardiopulmonary Exercise Testing (CPET) at Week 24 (time frame: Baseline, Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02875366, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2019.