Abstract 5767: Viral Anti-inflammatory Treatment of Unstable Coronary Syndromes: The VT-111 Acute Coronary Syndrome Trial
Background: Up-regulation of inflammatory responses contributes to coronary plaque rupture, thrombosis, and vascular occlusion leading to myocardial and cerebral infarction. Some viruses have developed potent proteins that block key steps in both the innate and adaptive immune responses. VT-111 is a viral serine proteinase inhibitor that demonstrates reductions in monocyte migration to sites of vascular damage in a wide range of animal models.
Methods: In a double-blind, placebo-controlled trial, the safety of VT-111 plus standard of care was evaluated in patients with acute coronary syndromes treated with stents. Patients received IV VT-111 or placebo once daily for 3 days, starting immediately before intervention. Patients were followed for 3 days in hospital, and at 14, 28 days and 3 and 6 months for safety/efficacy endpoints, including biomarker analysis and MACE (death, MI or revascularization). At 6 months, restenosis was evaluated by intravascular ultrasound.
Results: Forty-eight patients were enrolled at 7 sites; 19 patients received 5 μg/kg VT-111, 17 patients received 15 μg/kg and 12 patients received placebo. There were no differences between the treated and control groups on key safety endpoints, including coagulation parameters and adverse events. A trend towards a decrease in MACE was observed, with a reduction to 0% in the 15 μg/kg group from 18% in controls. A significant, dose-dependent reduction in Troponin I levels was observed with VT-111 at 8, 16, 24 and 54 hours post-dose (p<0.05). Similar reductions were observed in CK-MB levels at 8, 16 and 24 hours post-dose (p<0.05). Trends towards a reduction in MCP-1 were also observed. Further analysis suggests that VT-111 may also have early effects on markers such as EN-RAGE (S100A12), IL-6 and CD40L. There were no differences in in-stent plaque area or lumen area between control and treated groups, as assessed by IVUS.
Conclusion: This randomized, placebo-controlled trial supports the safety of 3 daily IV injections of VT-111, a first in class viral-derived anti-inflammatory therapeutic agent. A significant reduction in biomarkers of cardiac damage demonstrates the potential of this novel class of protein therapeutics.