Chronic Obstructive Pulmonary DiseasePhase 2NCT04066751
The Multicenter Topic Trial
A Phase 2 study testing Ivacaftor in people with Chronic Obstructive Pulmonary Disease, run by University of Alabama at Birmingham.
Trial summary
The purpose of this protocol is to test the safety, pharmacokinetics, and pharmacodynamics of the Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, ivacaftor in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- Ivacaftor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2021to 31 Oct 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or Female age 40-80
- A Clinical diagnosis of COPD as defined by GOLD
- At Least a 10 pack year smoking history
- Exhibit symptoms of chronic bronchitis as defined by the Medical Research Council
- FEV1% predicted ≥ 35% and ≤80% Post Bronchodilator
- Clinically stable in the last 4 weeks with no evidence of COPD exacerbation
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- Weight of 40 kg-120 kg
- Willingness to use at least one form of acceptable birth control including abstinence, condom with spermicide, or hormonal contraceptives from time of signing ICF through study follow up visit
- Willing to monitor blood glucose if known history of insulin dependent diabetes mellitus
- Capable of giving signed informed consent
Who cannot join
- Current Diagnosis of Asthma
- Known Diagnosis of Cystic Fibrosis
- Use of Continuous Oxygen Therapy of greater than 2 liters per minute - patients on 2 liters of Oxygen or less will be excluded if they have been hospitalized for COPD in the prior year or had more than 2 exacerbations requiring steroids and/or antibiotics in the prior year.
- Documented history of drug abuse within the last year
- Subjects should not have a pulmonary exacerbation or changes in therapy for pulmonary disease within 28 days before receiving the first dose of study drug.
- Cirrhosis or elevated liver transaminases > 3X ULN
Show all 19Show fewer
- GFR < 50 estimated by Cockroft-Gault
- Any illness or abnormal lab finding 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.
- Pregnant or Breastfeeding
- Subjects taking moderate or strong inhibitors or inducers of CYP3A4, including certain herbal medications and grapefruit juice. (Excluded medications and foods including the drugs and foods listed in the IRB HSP application.)
- Uncontrolled Diabetes
- Recent (e.g 1year) arterial thrombotic events (peripheral arterial disease, thrombotic stroke)
- Clinically significant arrhythmias requiring anti-arrhythmic agent(s) or conduction abnormalities that in the opinion of the investigator affect patient safety
- A standard digital ECG demonstrating QTc >450 msec for men and > QTc 470 msec for women at screening. If QTc exceeds 450 msec for men and > QTc 470 msec for women at the screening ECG, the ECG should be repeated 2 more times during the screening period, and the subject will be excluded if the average of the 3 QTc values is >450 msec for men and > QTc 470 msec for women.
- Angina symptoms
- History of MI or revascularization procedure within the last three years prior to screening
- Clinically significant congestive heart failure (known LVEF <= 45%, cor pulmonale, diastolic heart failure, etc)
- Patients with stable coronary artery disease are eligible
- History of stroke/CVA or non-skin cancer <5 years prior
About this study
Official title: A Multicenter Randomized, Double-blind, Phase 2, Placebo Controlled Study to Determine the Safety and Efficacy of Ivacaftor (VX-770) for the Treatment of Chronic Obstructive Pulmonary Disease (The Multicenter Topic Trial)
The purpose of this protocol is to test the safety, pharmacokinetics, and pharmacodynamics of the Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, ivacaftor in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis. 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 study is a multicenter, randomized, double-blind, placebo-controlled, stratified study of orally-administered ivacaftor.
Read the detailed description
Like CF, COPD is characterized by small airway mucus obstruction that is associated with accelerated loss of lung function and mortality. Our 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. Our 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 patient-reported outcomes (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.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- Ivacaftor
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IvacaftorDrug
Also called Kalydeco
Ivacaftor will be supplied as a tablet for oral administration, film-coated, 150 mg
| Study group | Role | What they receive |
|---|---|---|
| Ivacaftor | Active comparator | Ivacaftor, 150 mg PO every 12 hrs for 84 days Receives: Drug: Ivacaftor |
| Placebo | Placebo comparator | Placebo, 150 mg PO every 12 hrs for 84 days Receives: Drug: Ivacaftor |
What is being measured
The primary outcome is the main question the study is designed to answer.
CFTR activity
Change in peripheral CFTR activity as detected by sweat chloride testing
Measured: assessed at day1, day 28, day 56, and day 84
FEV1
Change in lung function as measured by FEV1 (Pulmonary Function testing.)
Measured: assesed at day 1, day 28, day 56, and day 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2019
- Study start1 Dec 2021 (estimated)
- Primary completion31 Oct 2024 (estimated)
- Study completion31 Oct 2024 (estimated)
Why it stopped: Study never started due to change in availability of study drug
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Vertex Pharmaceuticals Incorporated
- Responsible party
- Principal investigator, Mark Dransfield, MD, University of Alabama at Birmingham
- Investigators
- Mark Dransfield, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04066751
- Sponsor's protocol ID
- IRB-300003967
- Other IDs
- P30DK072482
- Status last verified
- Jan 2022
- First submitted
- 19 Aug 2019
- Last updated
- 27 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Randomized, Double-blind, Phase 2, Placebo Controlled Study to Determine the Safety and Efficacy of Ivacaftor (VX-770) for the Treatment of Chronic Obstructive Pulmonary Disease (The Multicenter Topic Trial)
- ClinicalTrials.gov ID
- NCT04066751
- Acronym / sponsor ID
- IRB-300003967
- Conditions
- Chronic Obstructive Pulmonary Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study never started due to change in availability of study drug
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Vertex Pharmaceuticals Incorporated
- Study start
- 1 Dec 2021 (estimated)
- Primary completion
- 31 Oct 2024 (estimated)
- Study completion
- 31 Oct 2024 (estimated)
- First posted
- 26 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this protocol is to test the safety, pharmacokinetics, and pharmacodynamics of the Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, ivacaftor in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis. 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 study is a multicenter, randomized, double-blind, placebo-controlled, stratified study of orally-administered ivacaftor.
Detailed description
Like CF, COPD is characterized by small airway mucus obstruction that is associated with accelerated loss of lung function and mortality. Our 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. Our 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 patient-reported outcomes (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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ivacaftor | Active comparator | Drug: IvacaftorIvacaftor, 150 mg PO every 12 hrs for 84 days |
| Placebo | Placebo comparator | Drug: IvacaftorPlacebo, 150 mg PO every 12 hrs for 84 days |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or Female age 40-80
- A Clinical diagnosis of COPD as defined by GOLD
- At Least a 10 pack year smoking history
- Exhibit symptoms of chronic bronchitis as defined by the Medical Research Council
- FEV1% predicted ≥ 35% and ≤80% Post Bronchodilator
Key exclusion criteria (19 listed)
- Current Diagnosis of Asthma
- Known Diagnosis of Cystic Fibrosis
- Use of Continuous Oxygen Therapy of greater than 2 liters per minute - patients on 2 liters of Oxygen or less will be excluded if they have been hospitalized for COPD in the prior year or had more than 2 exacerbations requiring steroids and/or antibiotics in the prior year.
- Documented history of drug abuse within the last year
- Subjects should not have a pulmonary exacerbation or changes in therapy for pulmonary disease within 28 days before receiving the first dose of study drug.
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 |
|---|---|---|
| IvacaftorAlso: KalydecoIvacaftor will be supplied as a tablet for oral administration, film-coated, 150 mg | Drug | Ivacaftor, Placebo |
Primary outcome
CFTR activity
Time frame: assessed at day1, day 28, day 56, and day 84
Change in peripheral CFTR activity as detected by sweat chloride testing
FEV1
Time frame: assesed at day 1, day 28, day 56, and day 84
Change in lung function as measured by FEV1 (Pulmonary Function testing.)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2022.
- Individual participant dataSharing planned: No
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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.
Mark Dransfield, MD principal investigator
University of Alabama at Birmingham
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ivacaftor in people with Chronic Obstructive Pulmonary Disease, run by University of Alabama at Birmingham.
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 10 inclusion and 19 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: withdrawn, as of the sponsor's last update on 27 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
CFTR activity (time frame: assessed at day1, day 28, day 56, and day 84). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jan 2022.