EMBRACE-STEMI: Phase II Clinical Trial
Stealth Peptides is initiating a multinational Phase II clinical trial with Bendavia™ focused on ischemia reperfusion injury in patients experiencing acute ST-segment elevation myocardial infarction (STEMI). The Phase II clinical trial is termed EMBRACE-STEMI™ for the Evaluation of the Myocardial effects of Bendavia for reducing Reperfusion injury in patients with Acute Coronary Events — ST-wave Elevation Myocardial Infarction. The trial will be a prospective, multicenter, randomized, double-blind, placebo-controlled, dose-ranging study designed to assess the safety, tolerability, and efficacy of intravenously administered Bendavia on a background of standard-of-care therapy for reduction of reperfusion injury in patients with acute, first time ST-wave elevation myocardial infarction.
The primary objective of EMBRACE-STEMI is to evaluate the impact of Bendavia on limiting the size of infarcted myocardium in patients who have undergone successful reperfusion using primary percutaneous coronary intervention (PCI) and stenting. Other objectives for the trial include:
- Microvascular dysfunction
- Renal dysfunction through 30 days and 6 months post-PCI and stenting
- Cardiac function through day 30 post-PCI
- The incidence of immediate myocardial complications during the primary hospitalization
- Biomarkers of congestive heart failure and systemic inflammation through 6 months
- Long-term clinical outcome at 30 days and 6 months
AMI clinical studies with Cyclosporine A
Recent data with Cyclosporine A (CsA), a drug that similarly prevents the opening of the mitochondrial permeability transition pore, support the potential for comparable success with Bendavia in Phase II trials. CsA has been shown to reduce infarct size in small animal models of coronary artery ischemia reperfusion.
In 2008, Piot et al. showed that this preclinical benefit could be reproduced in patients given the drug at the time of reperfusion during primary percutaneous coronary intervention (PCI) for acute, ST-segment elevation myocardial infarctions (STEMI). Follow-up of these patients by Mewton et al. showed that this initial benefit was maintained for at least 6 months.
- As with Bendavia, CsA targets the mitochondria and inhibits the opening of the mPTP
- 58 patients each with an acute ST-segment elevation myocardial infarction (STEMI) received either intravenous (IV) bolus CsA or normal saline (placebo) immediately prior to undergoing percutaneous coronary intervention (PCI)
- Infarct sizes as measured by creatine kinase (CK-MB) were significantly lower (by ~40%) as compared to placebo
- For a patient subgroup (n=28), the mass of infarcted tissue as measured by cardiac MRI (cMRI) was significantly lower with CsA (p=0.04) as compared to placebo
- The patient subgroup from the clinical study reported by the NEJM underwent a 6 month cMRI follow up to assess the long-term effects of CsA on left ventricular (LV) remodeling compared to placebo
- A statistically significant (p=0.04) infarct size reduction (29%) remained at 6 months for the CsA treated patients compared to placebo
- No significant differences were observed among patients given CsA or placebo with either regional wall thickness of remote non-infarcted myocardium or global LV mass
- CsA did not demonstrate detrimental effects on LV remodeling as compared to placebo treated patients
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