Study to Evaluate the Safety and Activity of BB3 to Treat Heart Attack

Study Overview
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Brief Summary
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The study will evaluate the effect of BB3 to preserve myocardial (heart) tissue and function following myocardial infarction (heart attack).

Detailed Description
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Percutaneous coronary intervention (PCI) has become the mainstay for treatment of ST-segment elevation myocardial infarction (STEMI). Whereas early recanalization undoubtedly salvages myocardial tissue, reperfusion following prolonged ischemia can also exacerbate injury. Infarct size needs to be limited, and the conditions favoring adaptive ventricular healing and remodeling optimized because in patients with acute myocardial infarction (AMI) who do not die of out-of-hospital arrhythmias, long-term prognosis is dependent on the amount of myocardium that is lost, and the outcome of ventricular remodeling. Angion Biomedical Corp. has identified BB3, a small molecule mimetic of hepatocyte growth factor/scatter factor (HGF/SF) whose activity is expected to preserve tissue viability and attenuate dysfunction in the setting of organ injury while obviating the logistical difficulties associated with gene or protein therapy. HGF/SF is a naturally occurring cell survival factor that holds significant therapeutic potential. BB3 has been shown to possess HGF/SF activities, including protection against heart injury following myocardial infarction. This study is designed to evaluate clinical efficacy of BB3 in patients presenting with acute ST segment elevation myocardial infarction (A-STEMI) who undergo PCI.

Official Title
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A Phase 2 Pilot Study to Evaluate the Safety and Activity of BB3 as an Adjunct to Percutaneous Coronary Intervention (PCI) in Subjects Presenting With Acute ST Segment Elevation Myocardial Infarction (STEMI)

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Drug: BB3
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject or legally authorized representative has been informed of the nature of the study, agrees to its provisions, and has been provided and signed written informed consent, approved by the Institutional Review Board (IRB), prior to performance of any study related procedure including screening procedure. Subject is male or female Subject is 21 to 80 years of age Estimated body weight < 120 kg and BMI < 40 Subject is experiencing clinical symptoms consistent with acute myocardial infarction (AMI) (e.g., chest pain, arm pain, etc.,) >30 minutes duration and unresponsive to nitroglycerin; with ST segment elevation of more than 1 mm in at least two contiguous leads of ECG or new or presumed new onset bundle branch block (BBB) Fulfills clinical center's criteria for primary PCI PCI will be done within 12 hours of onset of STEMI. The subject and his/her physician are willing to comply with the requirements of the study and the specified follow-up evaluations. If female, either surgically sterile or post-menopausal or using acceptable contraception and agree to use effective birth control regimen during the study period. Men must agree to use condoms during the study period. Women of child bearing potential must have a negative urine or serum pregnancy test. In the opinion of the Investigator, the subject is capable of understanding and complying with the protocol. Exclusion Criteria: Pregnant or nursing subjects and those who plan pregnancy in the period up to 6 months following index procedure. Cardiogenic shock (Killip class 4) or cardiac arrest History of prior myocardial infarction or pre-existing Q waves on ECG An elective surgical procedure is planned that would necessitate interruption of anti-platelet agents during the first six months post enrollment; Any contraindication to undergo MRI imaging. This will include any of the following exclusions: Cardiac pacemaker or implantable defibrillator; Non-MRI-compatible aneurysm clip; Neural stimulator (e.g., TENS-Unit); Any implanted or magnetically activated device (e.g., insulin pump); Any type of non-MRI-compatible metallic ear implant; Metal shavings in the orbits; Any metallic foreign body, shrapnel, or bullet in a location which the physician feels would present a risk to the subject; Any history indicating contraindication to MRI, including claustrophobia or allergy to gadolinium; Inability to follow breathhold instructions or to maintain a breathhold for >15 seconds; Irregular cardiac rhythm not expected to resolve after treatment of the acute cardiac condition (e.g., chronic atrial fibrillation) Known hypersensitivity or contraindication to gadolinium contrast. Subject has active bleeding or a history of bleeding diathesis or coagulopathy (including heparin induced thrombocytopenia), or refusal to receive blood transfusions if necessary; Subjects presenting with cardiogenic shock (SBP <80 mmHg for >30 minutes, or requiring IV pressors or emergency IABP for hypotension treatment) or cardiopulmonary resuscitation prior to randomization; History of intracerebral mass, aneurysm, arteriovenous malformation, or hemorrhagic stroke; stroke or transient ischemic attack within the past 6 months, or any permanent residual neurologic defect; known preceding cardiac ventricular arrhythmia Impaired renal function (eGFR of ≤30 ml/min/1.73m2, as estimated by the MDRD4v equation) or on dialysis. Impaired hepatic function (ALT > 2x upper limit of normal, or a total bilirubin greater than 1.5 x upper limit of normal). Currently participating in or has participated in an investigational drug or medical device study within 30 days or 5 half-lives, whichever is longer, prior to enrollment into this study Have an active malignancy or history of solid, metastatic, or hematologic malignancy with the exception of basal or squamous cell carcinoma of the skin that has been removed History of positive human immunodeficiency virus (HIV) test History of rheumatoid arthritis History of proliferative retinopathy or laser surgery for retinopathy Subjects who require cytochrome P450 1A2 (CYP1A2) inhibitors, ciprofloxacin and/or fluvoxamine (Luvox®) Subject has other medical illness or known history of substance abuse (alcohol, cocaine, heroin etc.) that may cause non-compliance with the protocol, confound the data interpretation or is associated with a limited life expectancy of less than 6 months, Any significant medical condition which in the Investigator's opinion may interfere with the subject's optimal participation in the study; Subject has a known hypersensitivity or allergy to stainless steel, nickel, cobalt chromium, nitinol, titanium or known hypersensitivity or allergy to contrast media (e.g. rash) that cannot effectively be controlled by premedication with steroids and/or diphenhydramine. Subjects with hypersensitivity or allergy to any of the components of the device (structural, drug or polymer components) and subjects with true prior anaphylaxis to contrast media should not be enrolled

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BB3<br>Daily intravenous administration of 2 mg/kg BB3 for four (4) days | Drug: BB3<br>* Daily intravenous administration of 2 mg/kg BB3 for four (4) days<br>|
| Placebo Comparator: Normal Saline<br>Daily intravenous administration for four (4) days | Drug: Normal saline<br>* Daily intravenous administration for four (4) days. The volume of normal saline will vary by estimated weight.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Reduction in Infarct Size | Evaluation of reduction in infarct size by MRI between the BB3 and placebo treatment groups at 6 months based on index of myocardial salvage | 6 month | 
| Evaluation of the Degree of Late Ventricular Remodeling | Evaluation of the degree of late ventricular remodeling between the BB3 and placebo treatment groups at 6 months, as measured by increase in LV end-diastolic volume index (LVEDVI) from initial MR image (day 5±1) to late MR image (6 months). | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CK-MB and Troponin |  | 6 months | 
| Change in BNP Levels |  | 6 months | 
| Change in Symptoms and Clinical Signs of CHF |  | 6 months | 
| Change in LVEDVI, LVESVI and LV Ejection Fraction (EF) After MI Assessed by Cine MR (SSFP Imaging) |  | 6 months | 
| LVEDVI, LVESVI and LVEF After MI Assessed by 2D and 3D Echocardiography |  | 6 months | 
| Change Between Initial Semi-quantitative Regional Wall Motion Score (17 Segment Model) by Echocardiography |  | 1 and 6 months | 
| Change in Regional Myocardial Radial, Circumferential and Longitudinal Strain |  | 1 and 6 months | 
| Frequency of MACE |  | 6 months | 
| Frequency of New Onset CHF Through 6 Months |  | 6 months | 
| Number of Hospitalizations for CHF Through 6 Months |  | 6 months | 
| Incidence of Complete ST Segment Resolution 60 ± 30 Minutes After Last Angiogram |  | 6 months | 
| Frequency of AE, SAEs |  | 6 months | 
| Frequency of MACCE |  | 6 months | 
| All-cause Mortality |  | 6 months | 
| Development of Ventricular Fibrillation or Other Life-threatening Arrhythmia |  | 6 months | 
| Change From Baseline eCrCl |  | 6 months | 
| Change in Body Weight |  | 6 months | 
| Symptoms and Clinical Signs of CHF | Symptoms and clinical signs of CHF measured by NYHA classification | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatocyte growth factor mimetic, hepatocyte growth factor(HGF), Myocardial Infarction, Acute ST Segment Elevation Myocardial Infarction (STEMI), Percutaneous Coronary Intervention (PCI)