March 15, 2015: The sponsor terminated the study early after some patients receiving pegnivacogin experienced severe allergic reactions.
The REG1 anticoagulation system is associated with a similar rate of ischemic events and more bleeding compared to bivalirudin monotherapy in patients undergoing percutaneous coronary intervention (PCI), according to the results of the REGULATE-PCI trial.
The results were presented Sunday in a late-breaking session at the annual Scientific Sessions of the American College of Cardiology in San Diego.
The DCRI’s John Alexander, MD, (pictured, right) is one of REGULATE-PCI’s co-principal investigators, along with A. Michael Lincoff, MD, of the Cleveland Clinic and Roxana Mehran, MD, of Mount Sinai’s Icahn School of Medicine. Thomas Povsic, MD, PhD, is a co-investigator from the DCRI.
The REGULATE-PCI study is a phase III trial intended to evaluate the efficacy and safety of REG1, a two-drug system that includes an RNA aptamer anticoagulant called pegnivacogin and an RNA aptamer reversal agent called anivamersen that binds to pegnivacogin and blocks its activity. REG1 was designed to give clinicians the ability to regulate the clotting effect with much more precision than is possible with the most widely used anticoagulation drugs, such as bivalirudin.
REGULATE-PCI’s academic leadership and sponsor, Regado Biosciences, terminated the study in August after some patients receiving pegnivacogin experienced severe allergic reactions. The decision to halt the trial was based on a Data and Safety Monitoring Board (DSMB) recommendation due to a serious allergic reaction event rate of 0.6 percent in the REG1 arm. The DSMB analyzed data from the first approximately 3,250 patients enrolled in what was intended to be a 13,200-patient trial.
An earlier, phase II study of REG1, the RADAR trial, also observed a small number of mild to moderate allergic reactions to the REG1 system.
“We had hoped to see a reduction in ischemic events and maybe also a reduction in bleeding compared to bivalirudin,” Alexander said. “We gave patients a high-dose anticoagulant during PCI and then turned it off with the reversal agent immediately after the procedure. We thought that might result in fewer ischemic events and less bleeding. Instead, in a smaller number of patients, we saw similar rates of ischemic events and slightly more bleeding with REG1 than with bivalirudin.”
Given the early termination of the trial and smaller number of patients and events than planned, any conclusion regarding the efficacy and safety of REG1 should be considered exploratory, Alexander said.
Alexander also noted that despite the disappointing outcome of REGULATE-PCI, the theory behind the potential promise of a reversible anticoagulant remains sound.
“On one hand, this is a negative trial but we learned a lot from it and will learn more from additional analyses,” he said. “We still have more to learn about why we did not see better efficacy and/or less bleeding and learn about the mechanism behind these unexpected allergic reactions. I believe people are still interested in the concept of a reversible anticoagulant. This is an idea that requires further study.”