A Phase 2 interventional study of Ivacaftor 150 MG and Placebo in Chronic Obstructive Pulmonary Disease and Chronic Bronchitis, sponsored by University of Alabama at Birmingham. Completed at 1 site in United States. Open to participants aged 40 Years to 80 Years. Per ClinicalTrials.gov, last updated 2024-12-12.
Sponsored by University of Alabama at Birmingham · Phase 2, Interventional, and Treatment
The study is a Phase 2 Study to establish the safety and efficacy of a drug called Ivacaftor (VX-770) in patients with chronic obstructive pulmonary disease (COPD), chronic bronchitis, and acquired CFTR dysfunction as detected by sweat chloride analysis. The design is a pilot, randomized (3:1, active:placebo), double-blind, placebo-controlled study. Approximately 40 subjects with COPD will be randomized.
Like CF, COPD is characterized by small airway mucus obstruction that is associated with accelerated loss of lung function and mortality. Preliminary data indicate that cigarette smoke exerts deleterious effects on airway epithelial function including the reduction of CFTR activity, enhanced mucus expression, and a pronounced reduction in mucociliary transport (MCT). Preliminary data also indicate that approximately 50% of patients with COPD have reduced CFTR activity, as detected in the upper airways, lower airways and sweat glands. Furthermore, CFTR dysfunction is independently associated with chronic bronchitis, can persist despite smoking cessation, and can be reversed by the CFTR potentiator ivacaftor (VX-770) in vitro by activating wild-type CFTR, resulting in a robust increase in MCT. Combined with unprecedented clinical improvement via augmented mucociliary clearance in CF patients with a responsive CFTR mutation treated with ivacaftor, these data indicate that CFTR represents a viable therapeutic target to address mucus stasis in a large subset of COPD patients (potentially representing over 4 million patients in the U.S. alone). This project will investigate the hypothesis that ivacaftor can augment CFTR activity in individuals with COPD who exhibit chronic bronchitis, resulting in meaningful improvements in epithelial function and respiratory health. The investigators' initial pilot study in patients with COPD and chronic bronchitis demonstrated that ivacaftor was safe, demonstrated stable pharmacokinetics, and exhibited a trend towards efficacy in measures of PROs and sweat chloride. The current trial will test the safety, pharmacokinetics, and pharmacodynamics of ivacaftor in a larger number of COPD patients with chronic bronchitis and for a longer treatment period, evaluating the potential of CFTR potentiator therapy to address acquired CFTR dysfunction in this population and set the stage for larger and longer-term trials in the future. Based on an IND already in place in the Rowe laboratory, an IRB familiar with the proposed study, an experienced clinical investigation team with expertise in all of the endpoints proposed, and a well characterized COPD population prioritized for the presence chronic bronchitis, CFTR dysfunction, and the absence of congenital CFTR mutations, the investigators are poised to deliver the trial.
Enrollment is planned at a single center, The University of Alabama at Birmingham. Patients will be randomized 3:1 to active drug (n=30) and placebo (10) to achieve the enrollment goal.
A sufficient number of subjects will be screened to randomize up to 50 subjects to achieve 40 completed subjects to receive either ivacaftor 150 mg BID (n=30) or placebo (n=10) for 84 days.
Ivacaftor and matching placebo will be orally administered as capsules according to the following guidelines:
Between study visit Day 1 and study visit Day 84, subjects will take 1 dose of study drug each day in the morning, beginning any time between 08:00 h (8:00 AM) and 12:00 h (12:00 PM). Whenever possible, subjects should take the study drug at the same time each day.
On the study visit days when PK samples are collected (study visit Days 1, 28, 56, and 84), the study drug is to be taken by the subject while he/she is at the study site
For visits after the Day 1 visit, subjects will be instructed to bring all remaining study drug materials to the site; study drug will be dispensed at each visit.
Ivacaftor will be prepared and dispensed by an unblinded pharmacist.
Subjects will be instructed to continue their standard COPD medication regimen.
209 studies on the registry are indexed under Bronchitis, Chronic; 14 are open to participants now.
This study's enrollment of 40 is below the median of 101 across 154 interventional studies indexed under Bronchitis, Chronic.
Browse Bronchitis, Chronic studies →University of Alabama at Birmingham is the lead sponsor of 1,421 studies on the registry; 277 are open to participants now.
Of its 164 completed or terminated interventional studies of FDA-regulated products, 130 (79%) have results posted.
Compared within Bronchitis, Chronic, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Pulmonary Disease, Chronic Obstructive. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
FEV1
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ivacaftor, 150 mg PO every 12 hrs for 84 days
Drug: Ivacaftor 150 MG
matching placebo
Drug: Placebo
Ivacaftor is a CFTR potentiator
Also known as: KALYDECO
placebo pills
Safety of Ivacaftor - Number of Participants With Adverse Events
Safety of ivacaftor will be determined by number of participants with adverse events (including serious adverse events).
Time frame: From Screening to Day 98
Safety of Ivacaftor - Number of Participants With Abnormal Serum Chemistry
Number of participants with abnormal serum chemistry values compared to screening values will also be used to determine safety of ivacaftor.
Time frame: From Screening to Day 98
Safety of Ivacaftor - Number of Participants With Abnormal Hematology
Safety of ivacaftor will also be determined by number of participants with abnormal changes in their screening hematology values.
Time frame: From Screening to Day 98
Safety of Ivacaftor - Number of Participants With Abnormal ECG (Prolonged QT Intervals)
Number of participants with abnormal changes in their screening ECGs is another factor that will be used to evaluate the safety of ivacaftor.
Time frame: From Screening to Day 98
Central CFTR Activity Measured by Mucociliary Clearance (MCC) Percentage Clearance at 60 Mins
Clearance of Tc99 sulfur colloid is a measure of MCC of the lungs, and is calculated by a standard protocol developed by the Cystic Fibrosis Therapeutics Development Network. The method provides a robust measure of MCC, and has been sensitive to the effects of inhaled pharmacologic agents in CF and COPD including improvements of an unprecedentedly large magnitude in CF patients with the G551D-CFTR mutation treated with ivacaftor measured in a multicenter study. The technique allows estimates of MCC in both the small and large airway compartments.
Time frame: From Screening to Day 84
Peripheral CFTR Activity Measured by Change in Sweat Chloride
Sweat chloride abnormality is correlated with COPD severity and symptoms, and is a highly sensitive outcome measure for CFTR-directed therapeutics. We have shown sweat chloride is sensitive to the presence of cigarette smoking and COPD, and the test has been successfully used as an endpoint in multiple CF trials, including studies to detect the efficacy of ivacaftor therapy.
Time frame: From Screening to Day 84
Indicators of Respiratory Function and COPD Health : Change in FEV1 Predict %
Spirometry is a standard outcome measure in COPD and a major indicator of efficacy and safety in COPD clinical trials. Post-bronchodilator spirometry will be performed by ATS criteria. FEV1 will be measured in predict percentage.
Time frame: From Screening to Day 84
San Diego Shortness of Breath Questionnaire (SOBQ)
The SOBQ is a self-reported questionnaire that assesses shortness of breath while performing a variety of activities of daily living. The Minimum Clinically Important Difference (MCID) is 5. The SOBQ includes 24 items, using 6-point scale with 0 = "not at all" to 5 = "maximal or unable to do because of breathlessness". The sum of SOBQ score ranges from 0 to 120, with higher score indicating more breathlessness.
Time frame: From D1 to Day 84
Breathlessness, Cough, and Sputum Scale (BCSS)
The BCSS is a three-item questionnaire rating breathlessness, cough and sputum on a 5-point Likert scale from 0 (no symptoms) to 4 (severe symptoms). The BCSS score ranges from 0 to 12; the higher the score indicates the worse of symptoms.
Time frame: From D1 to Day 84
COPD Assessment Test (CAT)
CAT is a self-reported questionnaire that measures COPD related quality of life. The MCID is 2. CAT composes of 8 questions, and the scores range from 0 - 40. Higher scores denote a more severe impact of COPD on a patient's life.
Time frame: From D1 to Day 84
St. George Respiratory Questionnaire (SGRQ)
The SGRQ is a disease-specific measure of health status for use in COPD with an MCID of 4. The scores range from 0 to 100, with higher scores indicating more limitations.
Time frame: From D1 to Day 84
| Milestone | Ivacaftor | Placebo |
|---|---|---|
| Started | 30 | 10 |
| Completed | 28 | 10 |
| Not completed | 2 | 0 |
| Withdrew: Death | 1 | 0 |
| Withdrew: Lost to follow-up | 1 | 0 |
Safety of ivacaftor will be determined by number of participants with adverse events (including serious adverse events).
| Participants | Ivacaftor | Placebo |
|---|---|---|
| Subject with any AE | 19 | 6 |
| AE resulting in drug interruption | 7 | 3 |
| AE resulting in drug discontinuation | 1 | 1 |
Number of participants with abnormal serum chemistry values compared to screening values will also be used to determine safety of ivacaftor.
| Participants | Ivacaftor | Placebo |
|---|---|---|
| Safety of Ivacaftor - Number of Participants With Abnormal Serum Chemistry | 0 | 0 |
Safety of ivacaftor will also be determined by number of participants with abnormal changes in their screening hematology values.
| Participants | Ivacaftor | Placebo |
|---|---|---|
| Safety of Ivacaftor - Number of Participants With Abnormal Hematology | 0 | 0 |
Number of participants with abnormal changes in their screening ECGs is another factor that will be used to evaluate the safety of ivacaftor.
| Participants | Ivacaftor | Placebo |
|---|---|---|
| Safety of Ivacaftor - Number of Participants With Abnormal ECG (Prolonged QT Intervals) | 1 | 1 |
Clearance of Tc99 sulfur colloid is a measure of MCC of the lungs, and is calculated by a standard protocol developed by the Cystic Fibrosis Therapeutics Development Network. The method provides a robust measure of MCC, and has been sensitive to the effects of inhaled pharmacologic agents in CF and COPD including improvements of an unprecedentedly large magnitude in CF patients with the G551D-CFTR mutation treated with ivacaftor measured in a multicenter study. The technique allows estimates of MCC in both the small and large airway compartments.
| percentage of clearance | Ivacaftor | Placebo |
|---|---|---|
| Screening | 88.4 ± 12 | 86.2 ± 7 |
| Day 84 | 86 ± 17 | 80 ± 2 |
Sweat chloride abnormality is correlated with COPD severity and symptoms, and is a highly sensitive outcome measure for CFTR-directed therapeutics. We have shown sweat chloride is sensitive to the presence of cigarette smoking and COPD, and the test has been successfully used as an endpoint in multiple CF trials, including studies to detect the efficacy of ivacaftor therapy.
| mmol/L | Ivacaftor | Placebo |
|---|---|---|
| Peripheral CFTR Activity Measured by Change in Sweat Chloride | 3.9 ± 9.8 | 3.8 ± 12.1 |
Spirometry is a standard outcome measure in COPD and a major indicator of efficacy and safety in COPD clinical trials. Post-bronchodilator spirometry will be performed by ATS criteria. FEV1 will be measured in predict percentage.
| predict percentage | Ivacaftor | Placebo |
|---|---|---|
| Indicators of Respiratory Function and COPD Health : Change in FEV1 Predict % | 1.5 ± 4.7 | -0.4 ± 7.6 |
The SOBQ is a self-reported questionnaire that assesses shortness of breath while performing a variety of activities of daily living. The Minimum Clinically Important Difference (MCID) is 5. The SOBQ includes 24 items, using 6-point scale with 0 = "not at all" to 5 = "maximal or unable to do because of breathlessness". The sum of SOBQ score ranges from 0 to 120, with higher score indicating more breathlessness.
| units on a scale | Ivacaftor | Placebo |
|---|---|---|
| San Diego Shortness of Breath Questionnaire (SOBQ) | -6.25 ± 26.8 | -8.6 ± 12.2 |
The BCSS is a three-item questionnaire rating breathlessness, cough and sputum on a 5-point Likert scale from 0 (no symptoms) to 4 (severe symptoms). The BCSS score ranges from 0 to 12; the higher the score indicates the worse of symptoms.
| units on a scale | Ivacaftor | Placebo |
|---|---|---|
| Breathlessness, Cough, and Sputum Scale (BCSS) | -0.6 ± 2.8 | -1.2 ± 1.3 |
CAT is a self-reported questionnaire that measures COPD related quality of life. The MCID is 2. CAT composes of 8 questions, and the scores range from 0 - 40. Higher scores denote a more severe impact of COPD on a patient's life.
| units on a scale | Ivacaftor | Placebo |
|---|---|---|
| COPD Assessment Test (CAT) | -0.7 ± 6.9 | -1 ± 6.7 |
The SGRQ is a disease-specific measure of health status for use in COPD with an MCID of 4. The scores range from 0 to 100, with higher scores indicating more limitations.
| score on a scale | Ivacaftor | Placebo |
|---|---|---|
| St. George Respiratory Questionnaire (SGRQ) | -7.6 ± 21.0 | -10.1 ± 10.6 |
Collected over Screening to Day 98. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ivacaftor | 19/29 (65.5%) | 6/29 (20.7%) | 0/29 (0%) |
| Placebo | 6/10 (60%) | 1/10 (10%) | 0/10 (0%) |
| Event | Ivacaftor | Placebo |
|---|---|---|
| Chest painRespiratory, thoracic and mediastinal disorders | 0/29 | 1/10 |
| PneumoniaRespiratory, thoracic and mediastinal disorders | 2/29 | 0/10 |
| AECOPDRespiratory, thoracic and mediastinal disorders | 2/29 | 0/10 |
| Altered mental statusPsychiatric disorders | 1/29 | 0/10 |
| DiarrheaGastrointestinal disorders | 1/29 | 0/10 |
| Age, Continuous(years) | Ivacaftor | Placebo | Total |
|---|---|---|---|
| Mean | 65.3 ± 7.9 | 65.9 ± 5.3 | 65.5 ± 7.3 |
| Sex: Female, Male(Participants) | Ivacaftor | Placebo | Total |
|---|---|---|---|
| Female | 11 | 6 | 17 |
| Male | 19 | 4 | 23 |
| Race (NIH/OMB)(Participants) | Ivacaftor | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 11 | 4 | 15 |
| White | 19 | 6 | 25 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Body Mass Index(kg/m^2) | Ivacaftor | Placebo | Total |
|---|---|---|---|
| Mean | 27.6 ± 5.7 | 28.0 ± 5.3 | 27.7 ± 5.6 |
| Current Smoker(Participants) | Ivacaftor | Placebo | Total |
|---|---|---|---|
| Count of participants | 20 | 4 | 24 |
| Smoking Exposure(pack/year) | Ivacaftor | Placebo | Total |
|---|---|---|---|
| Mean | 41.3 ± 25.2 | 27.8 ± 15.4 | 38.0 ± 22.7 |
PDFs hosted by the registry, ClinicalTrials.gov.
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Studies of the drug tested here: Ivacaftor
University of Alabama at Birmingham →