Study to Evaluate the Safety and Activity of BB3 to Treat Heart Attack
Condition: Myocardial Infarction
MeSH terms: Myocardial Infarction; ST Elevation Myocardial Infarction; Infarction
Intervention: BB3; Normal saline
Intervention description: Daily intravenous administration of 2 mg/kg BB3 for four (4) days; Daily intravenous administration for four (4) days. The volume of normal saline will vary by estimated weight.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 5.0
Sex: All
Minimum age: 21 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: hepatocyte growth factor mimetic; hepatocyte growth factor(HGF); Myocardial Infarction; Acute ST Segment Elevation Myocardial Infarction (STEMI); Percutaneous Coronary Intervention (PCI)

Summary:

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

Eligibility criteria:

        Inclusion Criteria:

          1. 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.

          2. Subject is male or female

          3. Subject is 21 to 80 years of age

          4. Estimated body weight < 120 kg and BMI < 40

          5. 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)

          6. Fulfills clinical center's criteria for primary PCI

          7. PCI will be done within 12 hours of onset of STEMI.

          8. The subject and his/her physician are willing to comply with the requirements of the
             study and the specified follow-up evaluations.

          9. 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.

         10. In the opinion of the Investigator, the subject is capable of understanding and
             complying with the protocol.

        Exclusion Criteria:

          1. Pregnant or nursing subjects and those who plan pregnancy in the period up to 6 months
             following index procedure.

          2. Cardiogenic shock (Killip class 4) or cardiac arrest

          3. History of prior myocardial infarction or pre-existing Q waves on ECG

          4. An elective surgical procedure is planned that would necessitate interruption of
             anti-platelet agents during the first six months post enrollment;

          5. Any contraindication to undergo MRI imaging. This will include any of the following
             exclusions:

               1. Cardiac pacemaker or implantable defibrillator;

               2. Non-MRI-compatible aneurysm clip;

               3. Neural stimulator (e.g., TENS-Unit);

               4. Any implanted or magnetically activated device (e.g., insulin pump);

               5. Any type of non-MRI-compatible metallic ear implant;

               6. Metal shavings in the orbits;

               7. Any metallic foreign body, shrapnel, or bullet in a location which the physician
                  feels would present a risk to the subject;

               8. Any history indicating contraindication to MRI, including claustrophobia or
                  allergy to gadolinium;

               9. Inability to follow breathhold instructions or to maintain a breathhold for >15
                  seconds;

              10. Irregular cardiac rhythm not expected to resolve after treatment of the acute
                  cardiac condition (e.g., chronic atrial fibrillation)

              11. Known hypersensitivity or contraindication to gadolinium contrast.

          6. Subject has active bleeding or a history of bleeding diathesis or coagulopathy
             (including heparin induced thrombocytopenia), or refusal to receive blood transfusions
             if necessary;

          7. 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;

          8. 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

          9. Impaired renal function (eGFR of ≤30 ml/min/1.73m2, as estimated by the MDRD4v
             equation) or on dialysis.

         10. Impaired hepatic function (ALT > 2x upper limit of normal, or a total bilirubin
             greater than 1.5 x upper limit of normal).

         11. 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

         12. 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

         13. History of positive human immunodeficiency virus (HIV) test

         14. History of rheumatoid arthritis

         15. History of proliferative retinopathy or laser surgery for retinopathy

         16. Subjects who require cytochrome P450 1A2 (CYP1A2) inhibitors, ciprofloxacin and/or
             fluvoxamine (Luvox®)

         17. 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,

         18. Any significant medical condition which in the Investigator's opinion may interfere
             with the subject's optimal participation in the study;

         19. 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