Safety, tolerability and effects of a single subcutaneous administration of SP16–a SERPIN-like, small peptide agonist of the Low-Density Lipoprotein-like Receptor 1 –on the acute inflammatory response in patients with ST-segment elevation Myocardial Infarction (STEMI)

Abstract

Background: Modulation of the inflammatory response is a promising therapeutic strategy in acute myocardial infarction. The novel approach is based on the anti-inflammatory and cytoprotective properties mediated by the engagement of the low-density lipoprotein-related protein 1 (LRP1) receptor. SERPIN peptide 16 (SP16) is a synthetic, selective LRP1 agonist. We herein present the results of a study with a single subcutaneous administration of SP16 in 10 patients with STEMI, to appraise its safety and tolerability and explore the effects on the acute inflammatory response, infarct size, and cardiac function.Methods: Ten patients with ST-segment elevation myocardial infarction (STEMI) were enrolled within 12 hours of symptoms onset and 6 hours of percutaneous coronary intervention in a singlecenter, single-arm, open-label study of a single subcutaneous administration of SP16 (0.2 mg/kg). Serial clinical biomarkers and echocardiography data were collected up to 12 months. The data are presented separately for the treatment group and compared with historical controls from a placebo-treated arm in a recently completed clinical trial (N = 28) with similar enrollment criteria.Results: All ten patients with STEMI received subcutaneous administration of SP16, minutes after percutaneous coronary intervention, without any treatment-related adverse events. The area under the curve for C-reactive protein was 133 [46-528] mg$d/L in the SP16-treated group versus 286 [141-581] mg$d/L in the historical placebo-treated group (P = 0.161). The area under the curve for creatine kinase-myocardial band was 1432 ng$d/mL in the SP16treated group versus 2367 ng$d/mL in the historical placebo-treated patients (P = 0.428). Left ventricular ejection fraction was 46% [39-54] at baseline and 51% [46][47][48][49][50][51][52][53][54][55][56][57][58] at 1 year follow-up in SP16-treated patients (interval change 5% [20.3% to +9%] P = 0.05) and 44% [38%-56%] at baseline and 53% [43%-59%] at 1 year followup in historical placebo-treated patients (interval change 3% [25% to 10%], P = 0.305). Conclusion:A single subcutaneous administration of SP16, a synthetic targeted LRP1 agonist, was safe and well-tolerated in patients with STEMI. A trend toward reduction in the inflammatory response and infarct size with SP16 was noted; however, the sample size for this study was not based on formal statistical criteria. More extensive studies are planned to determine the clinical efficacy of SP16 in STEMI. NCT: NCT04225533.