Coronary Artery DiseasePhase 1NCT00244647
A Phase 1b Study Evaluating RESTEN-MP in Subjects With Focal de Novo Stenosis
A Phase 1 study testing RESTEN-MP in people with Coronary Artery Disease and Coronary Stent Restenosis, run by Sarepta Therapeutics, Inc..
Trial summary
The process of re-narrowing of a coronary artery following a revascularization procedure such as angioplasty, begins at the time of the procedure. Restenosis has long been considered a major problem for effective long-term interventional success. Read more about this study
- Who is it for?
- Ages 19 to 80 years
- Conditions the study is for
- Coronary Artery Disease, Coronary Stent Restenosis
- What is being tested?
- RESTEN-MP
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- Aug 2003to not given
- Phase
- Phase 1
- 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 19 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 19 and ≤ 80 years of age.
- The Subject must be properly consented following FDA regulations and guidelines.
- Male and Female volunteers with reproductive or childbearing potential must agree to practice adequate birth control methods to protect themselves and partners from conception .
- Subjects will be scheduled for percutaneous coronary intervention (PCI) due to first time implantation of a Taxus Express stent as a result of stenosis.
- Subject is an acceptable candidate for coronary artery bypass surgery.
- The Subject has no more than two lesions within the coronary arterial system requiring stent placement where the diameter of the affected artery or arteries is
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- ≥ 2.5 mm and ≤ 4.9 mm based on angiography.
- The target lesion (and the secondary lesion, if applicable) is ≤ 20 mm in length via angiography.
- The Subject has had successful placement of a Taxus Express intracoronary stent(s).
- Subject agrees and is able to return for the scheduled study visits.
Who cannot join
- One or more treatable lesions within the coronary arterial system requiring planned or staged intervention prior to the Month One visit.
- Multi-vessel coronary artery disease involving more than 2 vessels within the coronary arterial system requiring stent placement.
- Clinically significant findings for any body system that the Principal Investigator determines will exclude a Subject from safely participating in the study.
- A pregnant or nursing female.
- Positive history for HIV, HBV or HCV.
- In-stent restenosis in the target vessel.
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- A target lesion located in an unprotected left main coronary artery or aorto-ostial location or in a bypass graft.
- Left ventricular ejection fraction < 30%.
- Angiographic evidence of the target vessel segment angulated ≥ 45º.
- Angiographic evidence of thrombus or severe calcification in the target lesion.
- History of bleeding disorders or coagulopathy.
- NYHA Class III congestive heart failure (CHF).
- Serum creatinine > 1.5 mg/dL.
- Clinically active cancer or any medical condition that may lead to study non-compliance or early study termination, confound the results, or is associated with limited life expectancy, i.e., less than 1 year.
- History of a stroke or trans-ischemic attack (TIA) within 6 months of angioplasty.
- Unstable ventricular arrhythmias.
- Evidence of an acute myocardial infarction within 72 hours of the intended treatment (defined as: Q wave or non-Q wave infarction having CK enzymes ≥ 2X the upper laboratory normal with the presence of a CK-MB elevated above the upper limit of normal) or acute myocardial infarction in progress at time of treatment.
- Known hypersensitivity to aspirin, clopidogrel, or heparin or a contraindication to receive the contrast agent administered during angiographic procedures.
- Unwilling to accept blood transfusions.
- Participant in an investigational device or drug study 30 days prior to randomization in this study.
- A stent other than the Taxus Express is placed.
- Unsuccessful intracoronary stent placement.
About this study
Official title: A Phase 1b, Randomized, Single Blind Study Evaluating RESTEN-MP in Subjects With Focal de Novo Stenosis
The process of re-narrowing of a coronary artery following a revascularization procedure such as angioplasty, begins at the time of the procedure. Restenosis has long been considered a major problem for effective long-term interventional success. This often results in repeated procedures to deal with recurrent stenosis (or restenosis) of the original targeted vessel.
There is a substantial body of literature suggesting that local MYC protein production in the injured coronary artery is a major stimulus and potential cause of restenosis that appears after stent placement. This study is based upon the hypothesis that stopping MYC protein production in the vessel has will help reduce restenosis (vessel re-narrowing).
Read more
AVI BioPharma Inc., has utilized its proprietary antisense chemistry to design a drug that interferes with MYC production.
This study will evaluate the safety, pharmacokinetics and potential effectiveness of a single intravenous slow-push dose of RESTEN-MP at the time of stent placement to reduce in-stent restenosis following balloon angioplasty and stent placement. The post-dose follow-up period is up to six-months.
Read the detailed description
The process of restenosis following a revascularization procedure, begins at the time of percutaneous coronary intervention (PCI). Restenosis has long been seen a major impediment of effective long-term interventional cardiology, necessitating repeated procedures to deal with in situ recurrent stenosis of the original targeted vessel. The restenosis rates are between 30 to 50% of patients treated with balloon angioplasty and between 15 to 30% of patients treated with bare metal stents. There is currently high enthusiasm for drug-eluting stents already approved for the market and which have an overall restenosis rate of <3% as reported in published reports for most clinical trial patient populations. However, there are subsets of patients (e.g., diabetic patients and patients with diffuse small vessel disease) that have restenosis rates around 10% despite the use of drug-eluting stents. It is probably too early to conclude that the currently approved drug-eluting stents are a panacea to relieve coronary arterial obstruction due to atherosclerotic heart disease. In fact, with the increased usage of the current drug-eluting stents on the market, there are reports of problems such as late stent malposition, subacute and late thromboses, and aneurysm formations due to the vessel toxicity associated with this method of treatment. There remains a definite need for a simple, safe and durable solution to restenosis.
The development of devices such as intravascular ultrasound has led to a greater understanding of restenosis mechanisms, especially after coronary artery stenting. It is presumed that the pathogenesis of coronary artery restenosis after a revascularization procedure entails two major processes. The first component (viz., recoil and remodeling) involves the mechanical collapse and constriction of the treated vessel; however, coronary stents provide luminal scaffolding that eliminates recoil and remodeling. The second component of coronary artery restenosis after a revascularization procedure is the endothelial response to injury. Whereas, the former focus in modulating the pathophysiological mechanisms involved in restenosis centered mainly on inhibition of platelet aggregation and function, current targets of pharmaceutical agents for this condition have shifted to inhibitors of the cell cycle, smooth muscle cell proliferation and migration, synthesis of extra-cellular matrix, and inflammatory mediators. Many different agents are currently being evaluated in pre-clinical and clinical studies.
AVI-4126, the active ingredient of RESTEN-MP, is a proprietary antisense drug designed to interfere with the ability of human <c-myc> gene to translate mRNA into MYC protein. Slow-push intravenous administration of RESTEN-MP in pharmacological doses in the restenosis porcine model prevented subsequent in-stent stenosis.
In addition to the standard safety assessments, assessments of the potential therapeutic value of RESTEN-MP as a neointimal hyperplasia inhibitor include late loss between the time of stent placement and 6 months thereafter.
- Conditions
- Coronary Artery Disease, Coronary Stent Restenosis
- Being tested
- RESTEN-MP
- Keywords
- restenosis, in-stent restenosis
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RESTEN-MPDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of a single IV slow-push injection of RESTEN-MP administered at the time of Taxus Express™ placement and over a six month surveillance period.
Secondary outcomes (2)
Pharmacokinetics of AVI-4126 when administered as RESTEN-MP.
Evidence of efficacy, based on coronary angiography and IVUS criteria for neointimal hyperplasia and restenosis changes over a 6-month period.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2005 (estimated)
- Study startAug 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by Sarepta Therapeutics, Inc.The 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind
- Enrolment
- 40 participants
Sponsor and investigators
- Lead sponsor
- Sarepta Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Thomas Porter, M.D., Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00244647
- Sponsor's protocol ID
- AVI-4126-CL-06
- Status last verified
- Apr 2008
- First submitted
- 25 Oct 2005
- Last updated
- 10 Apr 2008
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Randomized, Single Blind Study Evaluating RESTEN-MP in Subjects With Focal de Novo Stenosis
- ClinicalTrials.gov ID
- NCT00244647
- Acronym / sponsor ID
- AVI-4126-CL-06
- Conditions
- Coronary Artery Disease, Coronary Stent Restenosis
- Keywords
- restenosis, in-stent restenosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 40 participants
- Lead sponsor
- Sarepta Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Aug 2003
- First posted
- 27 Oct 2005 (estimated)
- 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 process of re-narrowing of a coronary artery following a revascularization procedure such as angioplasty, begins at the time of the procedure. Restenosis has long been considered a major problem for effective long-term interventional success. This often results in repeated procedures to deal with recurrent stenosis (or restenosis) of the original targeted vessel.
There is a substantial body of literature suggesting that local MYC protein production in the injured coronary artery is a major stimulus and potential cause of restenosis that appears after stent placement. This study is based upon the hypothesis that stopping MYC protein production in the vessel has will help reduce restenosis (vessel re-narrowing).
AVI BioPharma Inc., has utilized its proprietary antisense chemistry to design a drug that interferes with MYC production.
This study will evaluate the safety, pharmacokinetics and potential effectiveness of a single intravenous slow-push dose of RESTEN-MP at the time of stent placement to reduce in-stent restenosis following balloon angioplasty and stent placement. The post-dose follow-up period is up to six-months.
Detailed description
The process of restenosis following a revascularization procedure, begins at the time of percutaneous coronary intervention (PCI). Restenosis has long been seen a major impediment of effective long-term interventional cardiology, necessitating repeated procedures to deal with in situ recurrent stenosis of the original targeted vessel. The restenosis rates are between 30 to 50% of patients treated with balloon angioplasty and between 15 to 30% of patients treated with bare metal stents. There is currently high enthusiasm for drug-eluting stents already approved for the market and which have an overall restenosis rate of <3% as reported in published reports for most clinical trial patient populations. However, there are subsets of patients (e.g., diabetic patients and patients with diffuse small vessel disease) that have restenosis rates around 10% despite the use of drug-eluting stents. It is probably too early to conclude that the currently approved drug-eluting stents are a panacea to relieve coronary arterial obstruction due to atherosclerotic heart disease. In fact, with the increased usage of the current drug-eluting stents on the market, there are reports of problems such as late stent malposition, subacute and late thromboses, and aneurysm formations due to the vessel toxicity associated with this method of treatment. There remains a definite need for a simple, safe and durable solution to restenosis.
The development of devices such as intravascular ultrasound has led to a greater understanding of restenosis mechanisms, especially after coronary artery stenting. It is presumed that the pathogenesis of coronary artery restenosis after a revascularization procedure entails two major processes. The first component (viz., recoil and remodeling) involves the mechanical collapse and constriction of the treated vessel; however, coronary stents provide luminal scaffolding that eliminates recoil and remodeling. The second component of coronary artery restenosis after a revascularization procedure is the endothelial response to injury. Whereas, the former focus in modulating the pathophysiological mechanisms involved in restenosis centered mainly on inhibition of platelet aggregation and function, current targets of pharmaceutical agents for this condition have shifted to inhibitors of the cell cycle, smooth muscle cell proliferation and migration, synthesis of extra-cellular matrix, and inflammatory mediators. Many different agents are currently being evaluated in pre-clinical and clinical studies.
AVI-4126, the active ingredient of RESTEN-MP, is a proprietary antisense drug designed to interfere with the ability of human <c-myc> gene to translate mRNA into MYC protein. Slow-push intravenous administration of RESTEN-MP in pharmacological doses in the restenosis porcine model prevented subsequent in-stent stenosis.
In addition to the standard safety assessments, assessments of the potential therapeutic value of RESTEN-MP as a neointimal hyperplasia inhibitor include late loss between the time of stent placement and 6 months thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind
Who may qualify
- Ages
- 19 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- ≥ 19 and ≤ 80 years of age.
- The Subject must be properly consented following FDA regulations and guidelines.
- Male and Female volunteers with reproductive or childbearing potential must agree to practice adequate birth control methods to protect themselves and partners from conception .
- Subjects will be scheduled for percutaneous coronary intervention (PCI) due to first time implantation of a Taxus Express stent as a result of stenosis.
- Subject is an acceptable candidate for coronary artery bypass surgery.
Key exclusion criteria (22 listed)
- One or more treatable lesions within the coronary arterial system requiring planned or staged intervention prior to the Month One visit.
- Multi-vessel coronary artery disease involving more than 2 vessels within the coronary arterial system requiring stent placement.
- Clinically significant findings for any body system that the Principal Investigator determines will exclude a Subject from safely participating in the study.
- A pregnant or nursing female.
- Positive history for HIV, HBV or HCV.
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 |
|---|---|---|
| RESTEN-MP | Drug | – |
Primary outcome
Safety of a single IV slow-push injection of RESTEN-MP administered at the time of Taxus Express™ placement and over a six month surveillance period.
2 secondary outcomes
Pharmacokinetics of AVI-4126 when administered as RESTEN-MP.
Evidence of efficacy, based on coronary angiography and IVUS criteria for neointimal hyperplasia and restenosis changes over a 6-month period.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2008.
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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.
Thomas Porter, M.D. principal investigator
University of Nebraska
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RESTEN-MP in people with Coronary Artery Disease and Coronary Stent Restenosis, run by Sarepta Therapeutics, Inc..
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 22 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: stopped early, as of the sponsor's last update on 10 Apr 2008. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 stopped early. Results are not available in the source record.
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?
Safety of a single IV slow-push injection of RESTEN-MP administered at the time of Taxus Express™ placement and over a six month surveillance period.. 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 10 Apr 2008.