OrbusNeich Initiates HARMONEE Study in Japan

February 26, 2014—OrbusNeich (Fort Lauderdale, FL) announced that patient enrollment has been initiated in Japan in the HARMONEE (Harmonized Assessment by Randomized, Multicenter Study of OrbusNeich’s Combo Stent) study, which is the pivotal clinical trial of the company’s Combo dual-therapy stent. The trial employs a single Japan-United States protocol conducted as a global clinical trial “proof of concept” under the framework of the joint Japan-United States Harmonization-By-Doing initiative.

According to the company, the randomized, multicenter HARMONEE study is designed to enroll 572 patients at up to 50 sites in Japan and the United States to support the company’s planned application for Shonin approval in Japan and to meet the pilot trial requirements in the United States. Currently, the Combo dual-therapy stent is an investigational device and is not available for sale in Japan nor the United States. The Combo stent has, however, received CE Mark approval in Europe.

The company stated that the Combo dual-therapy stent accelerates endothelial coverage and controls neointimal proliferation through the combination of its prohealing technology with an abluminal sirolimus drug elution delivered from a biodegradable polymer that achieves full and complete dissipation by 90 days. OrbusNeich’s endothelial progenitor cell (EPC)-capture technology promotes the accelerated natural healing of the vessel wall after the implantation of blood-contact devices, such as stents. The technology consists of an antibody surface coating that captures EPCs circulating in the blood to the device to form an endothelial layer that provides protection against thrombosis and modulates restenosis.

The HARMONEE study’s Coprincipal Investigator, Shigeru Saito, MD, enrolled the first patient at Shonan Kamakura General Hospital in Okamoto, Kamakura City, Japan. Dr. Saito is Vice Director of the hospital.

In OrbusNeich’s press release, Dr. Saito commented, “This registration trial is an important milestone for interventional cardiologists and patients in Japan. 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-US collaboration, such that one can say that the first step to ‘creating the future’ has just been taken.”

In the HARMONEE study, patients presenting with ischemic coronary disease and non–ST-segment myocardial infarction will be randomized 1:1 to treatment with a Combo stent or an everolimus-eluting stent comparator. The study’s primary endpoint is a comparison of clinically driven target vessel failure, defined as cardiac death, target vessel myocardial infarction, 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.

The HARMONEE study design consists of three cohorts, each with an 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 6 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.

HARMONEE Coprincipal Investigator Mitchell Krucoff, MD, of Duke University Medical Center in Durham, North Carolina, stated in the company’s announcement, “The Japan-United States 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 coenrollment in both Japan and the United States 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!”

On February 21, OrbusNeich announced that the Combo dual-therapy stent was featured at the Joint Interventional Meeting 2014 in Rome, Italy. Robbert de Winter, MD, of the Academic Medical Center, in Amsterdam, the Netherlands, presented an update on the REMEDEE Registry, a postmarket registry to evaluate the long-term safety and performance of the Combo stent in routine clinical practice, confirming that the registry is three-quarters of the way to its goal of enrolling 1,000 patients.

Prof. de Winter commented, “The Combo technology has been one of the most innovative advancements in the interventional cardiology field for some time. I appreciate OrbusNeich's commitment to continued research and development and the advancement of stent technology for the benefit of our patients. This is an exciting technology, and I look forward to the results of the REMEDEE registry.”

The Combo stent was also featured in two live case demonstrations. The first live case was performed at Bonn University Hospital in Bonn, Germany. An 82-year-old woman with a history of myocardial infarction had a lesion in the left anterior descending artery. The Combo stent that was placed was 2.5 mm in diameter X 13 mm in length and resulted in a complete restoration of TIMI flow.

The second live case was performed at the Columbus Hospital in Milan, Italy. The patient had a calcified lesion of the left anterior descending artery, and four Combo stents were placed in the proximal (3.5 X 9 mm), medium (3.5 X 18 mm), medium distal (3.5 X 33 mm), and distal (2.5 X 23 mm) segments. In addition, OrbusNeich’s Sapphire NC balloons were used, advised the company.