Study to Evaluate the Safety and Activity of BB3 to Treat Heart Attack - Full Text View

Purpose

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

Condition	Intervention	Phase
Myocardial Infarction	Drug: BB3 Drug: Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	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)

Resource links provided by NLM:

MedlinePlus related topics: Heart Attack

U.S. FDA Resources

Further study details as provided by Angion Biomedica Corp:

Primary Outcome Measures:

Evaluation of reduction in infarct size [ Time Frame: 1 month ] [ Designated as safety issue: No ]
Evaluation of reduction in infarct size between the BB3 and placebo treatment groups at 1 month.
Evaluation of the degree of late ventricular remodeling [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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).

Secondary Outcome Measures:

Change in CK-MB and troponin [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Change in BNP levels [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Change in symptoms and clinical signs of CHF [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Change in LVEDVI, LVESVI and LV ejection fraction (EF) after MI assessed by cine MR (SSFP imaging) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
LVEDVI, LVESVI and LVEF after MI assessed by 2D and 3D echocardiography [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Change between initial semi-quantitative regional wall motion score (17 segment model) by Echocardiography [ Time Frame: 1 and 6 months ] [ Designated as safety issue: No ]
Change in regional myocardial radial, circumferential and longitudinal strain [ Time Frame: 1 and 6 months ] [ Designated as safety issue: No ]
Frequency of MACE [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Frequency of new onset CHF through 6 months [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Number of hospitalizations for CHF through 6 months [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Incidence of complete ST segment resolution 60 ± 30 minutes after last angiogram [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Frequency of AE, SAEs [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Frequency of MACCE [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
All-cause mortality [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Development of ventricular fibrillation or other life-threatening arrhythmia [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Change from baseline eCrCl [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Change in body weight [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	80
Study Start Date:	July 2012
Estimated Study Completion Date:	November 2014
Estimated Primary Completion Date:	July 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: BB3 small molecule mimetic of hepatocyte growth factor/scatter factor	Drug: BB3 Daily intravenous administration of 2 mg/kg BB3 for four (4) days
Placebo Comparator: Placebo Normal saline	Drug: Placebo Daily intravenous administration for four (4) days. The volume of normal saline will vary by estimated weight.

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.

Eligibility

Ages Eligible for Study:	21 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Signed informed consent
Estimated body weight < 120 kg and BMI < 30
Subject is experiencing clinical symptoms consistent with acute myocardial infarction (AMI)
Fulfills clinical center's criteria for primary PCI
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.
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 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 or on dialysis.
Impaired hepatic function
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01539590

Locations

United States, Connecticut
Yale University Medical Center	Recruiting
New Haven, Connecticut, United States, 06520
Contact: Laurie Thomas 203-737-8320 laurie.thomas@yale.edu
Contact: Louise Gambone 203-737-3427 louise.gambone@yale.edu
Principal Investigator: Frank Giordano, MD
United States, Minnesota
Minneapolis Heart Institute Foundation	Recruiting
Minneapolis, Minnesota, United States, 55407-1139
Contact: Susan Jagger, RN, BSN, CCRC 612-863-7065 susan.jagger@allina.com
Principal Investigator: Jay Traverse, MD

Sponsors and Collaborators

Angion Biomedica Corp

National Heart, Lung, and Blood Institute (NHLBI)

More Information

No publications provided

Responsible Party:	Angion Biomedica Corp
ClinicalTrials.gov Identifier:	NCT01539590 History of Changes
Other Study ID Numbers:	001-10, 5R44HL091699-03
Study First Received:	February 22, 2012
Last Updated:	July 13, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Angion Biomedica Corp:

hepatocyte growth factor mimetic
hepatocyte growth factor(HGF)
Myocardial Infarction
Acute ST Segment Elevation Myocardial Infarction (STEMI)
Percutaneous Coronary Intervention (PCI)

Additional relevant MeSH terms:

Heart Diseases
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia

Cardiovascular Diseases
Vascular Diseases
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 13, 2013