OrbusNeich today announced that patient enrollment has been initiated in Japan in the pivotal clinical trial of the COMBO Dual Therapy Stent(tm) (COMBO Stent) employing a single Japan-U.S. protocol conducted as a Global Clinical Trial "proof-of-concept" under the framework of the joint Japan-U.S. Harmonization-By-Doing [HBD] initiative. The first patient was enrolled at Shonan Kamakura General Hospital, Japan, by Dr. Shigeru Saito, M.D., the vice director of the hospital and co-principal investigator of the study.

The randomized, multi-center HARMONEE (Harmonized Assessment by Randomized, Multi-center Study of OrbusNEich's COMBO StEnt) study is designed to enroll 572 patients at up to 50 sites in Japan and the U.S. to support the company's planned application for Shonin approval in Japan and to meet the Pilot trial requirements in the U.S. Patients presenting with ischemic coronary disease and non-ST segment myocardial infarction (NSTEMI) will be randomized one-to-one to treatment with a COMBO Stent or an everolimus-eluting stent (EES) comparator.  The study's primary endpoint is a comparison of clinically driven target vessel failure (TVF), defined as cardiac death, target vessel myocardial infarction (MI) or ischemia-driven target vessel revascularization (TVR) by percutaneous or surgical methods. All patients will undergo fractional flow reserve (FFR) or angiography to determine ischemia-driven TVR.

"This registration trial is an important milestone for interventional cardiologists and patients in Japan," said Dr. Saito. "The study will investigate the clinical performance of the groundbreaking COMBO Stent, which combines drug eluting technology for control of neointimal proliferation along with EPC capture technology for promoting early endothelialization. Furthermore, this trial design innovates on the traditional framework for clinical trials using a unique Japan-U.S. collaboration, such that one can say that the first step to "creating the future" has just been taken."

The HARMONEE study design consists of three cohorts, each with equal number of patients receiving either the COMBO Stent or the control stent. The first cohort includes 30 patients who will undergo assessment by FFR and quantitative coronary angiography (QCA) at 12 months and optical coherence tomography (OCT) at six and 12 months. The second cohort consists of 110 patients who will undergo assessment by FFR, QCA and OCT at 12 months. The third cohort of 432 patients will undergo assessment by FFR and QCA at 12 months.

Mitchell Krucoff, M.D., of Duke University Medical Center, Durham, N.C., and study co-principal investigator, said, "The Japan-U.S. HARMONEE study is very exciting for the future of patient care and of clinical trials treating coronary disease. While the field of drug eluting stents is mature, the HARMONEE study breaks new ground with many important "firsts." This is the first four-component drug eluting stent to seek registration, combining healthier stent-site healing through biological capture of circulating endothelial progenitor cells to other "best in class" safety features such as sirolimus elution through abluminal coated, bioabsorbable polymer. And this is the first pivotal stent study where co-enrollment in both Japan and the U.S. will help bring forward this new device in both nations through regulatory harmonization. Finally, this is the first stent study using both physiologic and anatomic assessment of the long-term result, as well as high resolution imaging of endothelial recovery. This is certainly not "just another" stent study!"