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

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)

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

Study Overview

• Status: Terminated
• Conditions: Myocardial Infarction
• Intervention / Treatment: Drug: BB3; Drug: Normal saline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417-1139
      • Minneapolis Heart Institute Foundation
  • New York
    • New Haven, New York, United States, 06520
      • Yale University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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 Body Weight		6 months
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
Symptoms and Clinical Signs of CHF	Symptoms and clinical signs of CHF measured by NYHA classification	6 months

Collaborators and Investigators

• Sponsor: Angion Biomedica Corp
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Study Director: Weizhong Cai, Sponsor GmbH

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: February 22, 2012
• First Submitted That Met QC Criteria: February 22, 2012
• First Posted (Estimate): February 27, 2012

Study Record Updates

• Last Update Posted (Estimate): November 21, 2014
• Last Update Submitted That Met QC Criteria: November 7, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Myocardial Infarction; Percutaneous Coronary Intervention (PCI); hepatocyte growth factor mimetic; hepatocyte growth factor(HGF); Acute ST Segment Elevation Myocardial Infarction (STEMI)
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction
• Other Study ID Numbers: 001-10; 5R44HL091699 (U.S. NIH Grant/Contract)