Hong Kong-based OrbusNeich has initiated patient enrolment in the HARMONEE study being conducted for evaluating the Combo dual-therapy stent, designed to address the challenges of delayed healing of the coronary artery associated with monotherapy drug-eluting stents in Japan.
It is reportedly the first dual-therapy stent to both accelerate endothelial coverage and control neointimal proliferation through the combination of a proven pro-healing technology with an abluminal sirolimus drug elution delivered from a biodegradable polymer that achieves complete dissipation by 90 days.
The technology is composed of an antibody surface coating that captures endothelial progenitor cells (EPCs) to the device to form an endothelial layer that provides protection against thrombosis and modulates restenosis.
Vice-director of the hospital and co-principal investigator of the study, Dr Shigeru Saito enrolled the first patient at Shonan Kamakura General Hospital, Japan.
The randomised, multi-centre HARMONEE (Harmonized Assessment by Randomized, Multi-center Study of OrbusNEich’s COMBO StEnt) study is aiming for 572 patients at more than 50 sites across the US and Japan.
The two-country COMBO trial will proceed under a single protocol set by the FDA’s ‘Harmonization By Doing’ (HBD) initiative, announced as a pilot programme in 2010.
According to the FDA, HBD is an international effort to develop global clinical trials and address regulatory barriers that may be hold-up device approvals.
The study will randomise one-to-one to treat with a COMBO stent or an everolimus-eluting stent (EES) comparator in patients with ischemic coronary disease and non-ST segment myocardial infarction (NSTEMI). The primary endpoint is a comparison of clinically driven target vessel failure (TVF).
Dr Saito said 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," Dr Saito added.
"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."
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 will comprise 30 patients undergoing assessment by fractional flow reserve (FFR) and quantitative coronary angiography (QCA) at one year and optical coherence tomography (OCT) at six and 12 months.
In the second cohort, 110 patients will undergo assessment by FFR, QCA and OCT at one year, while 432 patients in the third cohort will undergo assessment by FFR and QCA at one year.
According to the company, HARMONEE 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.
Duke University Medical Center, Durham, North Carolina, Dr Mitchell Krucoff was the study co-principal investigator.
"The Japan-US HARMONEE study is very exciting for the future of patient care and of clinical trials treating coronary disease," Krucoff said.
"This is the first pivotal stent study where co-enrolment in both Japan and the US will help bring forward this new device in both nations through regulatory harmonisation."
In May 2013, the companies obtained CE mark for the Combo dual therapy stent, which was later introduced in Europe and select markets in Asia Pacific and the Middle East.
Combo dual-therapy stent is currently an investigational device and not available for sale in Japan and the US.
Image: OrbusNeich exterior. Photo: courtesy of Lenarussopartners.