• Interventional Techniques & Devices Myocardial Infarction
• Cardiology Clinical Trials

• Interventional Techniques & Devices
• Cardiology & Cardiovascular Medicine
• Myocardial Infarction
• Cardiology Clinical Trials

A single dose of inclacumab, a fully human recombinant monoclonal antibody directed against P-selectin, appears to reduce myocardial damage in patients undergoing percutaneous coronary intervention (PCI) as measured by biomarker concentration. Results from a randomized Phase 2 trial showed a reduction in levels of troponin I at 16 and 24 hours post PCI with a single dose of incalcumab 20 mg/kg when administered prior to PCI.

P-selectin is an adhesion molecule expressed on activated endothelial cells. It modulates interactions between white blood cells and platelets, acting as a crossroads of inflammation and thrombosis. It has been hypothesized that inhibition of P-selectin may reduce myocardial damage in the setting of PCI through both anti-inflammatory and anti-thrombotic effects.

The effect of a single dose of inclacumab on myocardial damage was examined in the Study of RO4905417 in Patients With Non ST-Elevation Myocardial Infarction (NSTEMI) Undergoing Percutaneous Coronary Intervention [SELECT-ACS; Tardif JC et al. J Am Coll Cardiol 2013]. Results were presented by Jean-Claude Tardif, MD, Montreal Heart Institute, Montreal, Quebec, Canada.

SELECT-ACS randomized NSTEMI patients to a single infusion of 5 or 20 mg/kg of inclacumab or matching placebo, administered 1 to 24 hours prior to PCI. To be eligible, patients had to be scheduled for catheterization and intended to undergo PCI. The primary endpoint was the change in troponin I (Tn-I) at 16 and 24 hours post PCI.

Of the 544 patients randomized, the efficacy analysis included 322 patients who received study medication, underwent PCI and had biomarkers assayed at all timepoints.

The duration of PCI and rates of drug-eluting and bare-metal stent deployment were similar between the 3 arms, as were use of concomitant medications.

The mean percent change in Tn-I was −22.4% at 16 hours (p=0.07) and −24.4% (p=0.05) for patients receiving inclacumab 20 mg/kg relative to those receiving placebo. Peak Tn-I was numerically reduced by 23.8% with this dose (p=0.05). There was no significant difference in Tn-I concentration observed with inclacumab 5 mg/kg at either timepoint.

The percent change in Tn-I at 24 hours with inclacumab 20 mg/kg versus placebo was similar in patients with or without diabetes (−33.2% and vs −31.6% respectively; p=0.03 in patients without diabetes; Table 1).

The change in creatine kinase-myocardial band (CK-MB) was similar to the findings for troponin with a borderline significant result in favor of high-dose inclacumab (−17.4% vs placebo; p=0.06). The incidence of CK-MB increases more than 3 times the upper limit of normal was 18.3% in the placebo group and 8.9% in the inclacumab 20 mg/kg group (p=0.05).

Safety data were collected at 120 days, at which time there was no increase in the rates of infection or bleeding with inclacumab. Of note, there were higher numbers of deaths (6 vs 0) and nonfatal MI (11 vs 2) in patients randomized to inclacumab versus placebo but the study was not adequately powered to detect differences in clinical endpoints.

While these findings show a favorable pattern in biomarker concentration with high-dose inclacumab in the setting of PCI for NSTEMI, the clinical relevance of these findings is not clear from this Phase 2 study. Further clinical investigation is required to determine the clinical impact of inclacumab administration in patients presenting with MI.

• © 2013 MD Conference Express®