In a study presented today at the American College of Cardiology’s Innovation in Intervention: i2 Summit in New Orleans, La., a team from the Duke Clinical Research Institute presented the results from a Phase 1 study evaluating a novel protein kinase C inhibitor that had shown benefit in animal models, but had not previously been studied in humans. This first-in-human study suggests that this new drug may have promise as a potential therapeutic agent in heart attack patients. Innovation in Intervention: i2 Summit is an annual meeting for practicing cardiovascular interventionalists sponsored by the American College of Cardiology in partnership with the Society for Cardiovascular Angiography and Interventions.
Heart attacks are caused by blockages in the coronary artery preventing blood flow to the heart muscle. Restoring blood flow to the heart improves clinical outcomes in heart attack patients, but there remains significant injury to heart muscle cells. Protein kinase C (PKC) is activated in these heart cells, initiating a series of events that can cause further damage to the heart. Animal studies have suggested that KAI-9803, an inhibitor of PKC, may reduce injury in damaged heart muscle cells, but this class of therapies had not previously been studied in heart attack patients.
In the DELTA MI trial, the DCRI team evaluated KAI-9803 in 154 patients with anterior ST-elevation MI undergoing primary percutaneous coronary intervention with balloon angioplasty and coronary stent implantation. Patients were randomized 2:1 to receive intracoronary injections of the active study drug (KAI-9803) vs. placebo in four dose groups (0.05, 0.5, 1.25 or 5.0 mg of KAI-9803). Researchers performed tests to assess heart function at various time points and a ssessed safety and cardiac outcomes through six months. This trial was designed as an exploratory study to assess the potential impact of KAI-9803 in this “first-in-human?study.
Results indicate that KAI-9803 may be associated with less myocardial necrosis with lower CK-MB AUC values at all dose levels. Furthermore, improved tissue perfusion (measured during coronary angiography after stent implantation and by continuous electrocardiogram recordings) and reduced infarct size (measured 14 days after the heart attack) were observed at the 0.5 mg (infarct size 23 vs. 29.5% of the left ventricle) and 1.25 mg (infarct size 32.5 vs. 43% of the left ventricle) dose levels. No major safety concerns were demonstrated with the therapy since the incidence of serious adverse events was similar among patients treated with KAI-9803 compared to placebo, even at the highest dose levels of the study.
"In this early study, we believe the data suggest a potential therapeutic role for KAI-9803,?said Matthew Roe, M.D., of the Duke Clinical Research Institute and lead author of the study. “The drug was associated with a favorable safety and tolerability profile and based on this ‘first in human?trial, we are interested in pursing larger studies to determine the therapeutic value of this treatment for heart attack patients receiving reperfusion therapy."