Safety & Performance Study of the FANTOM Sirolimus-Eluting Bioresorbable Coronary Scaffold

Coronary arteries, which supply blood to the heart muscle, are particularly
susceptible to the buildup of plaque, which can block or inhibit blood flow.
The process of arterial narrowing is referred to as atherosclerosis, or
coronary artery disease. If the coronary arteries become too narrow, cardiac
tissue may become starved of nutrients and oxygen, especially during exercise
when myocardial oxygen consumption increases, and pain (angina) may occur. As
vessel narrowing becomes more severe, death of myocardial muscle cells
downstream from the occlusion can occur due to the lack of oxygen. The sudden
death of these myocardial cells can result in a life threatening heart attack
(myocardial infarction).

Coronary artery disease accounts for the greatest mortality among all forms of
heart disease. Given the staggering morbidity and mortality associated with
coronary artery disease, any effort to return these patients to a productive,
pain-free existence is undeniably worthwhile and valuable to the individual and
society.

Coronary balloon angioplasty is a minimally invasive method of opening blocked
arteries. The procedure is more formally known as *PTCA* (percutaneous
transluminal coronary angioplasty). While angioplasty is successful in
restoring blood flow initially, restenosis or renarrowing of the treated vessel
occurs within six months in about 40% of cases.

To address this problem a device called a coronary stent was developed to
improve the clinical outcome after PTCA. The introduction of stents in the
early 1990s was a major breakthrough in the treatment of restenosis. A stent is
a flexible metal wire mesh tube, typically made from stainless steel alloys.
Coronary stents are typically mounted on a balloon and expanded during
implantation to the desired diameter. It was found that the implantation of a
stent reduces the incidence of restenosis to roughly 20% to 30%.

Currently stents are used in approximately 90% of all interventional procedures
worldwide.

The next major development in this endeavor came in the form of a combination
drug-device known as a Drug-Eluting Stent (DES). These metal stents commonly
combine a thin polymer coating and therapeutic drug that inhibits the build-up
of tissue during wound healing after stent delivery.
The most recent DES clinical trials demonstrated a restenosis rate of less than
10%.

In spite of these significant advancements, the use of metal-based drug-eluting
stents that remain permanently embedded within the arterial wall still has a
number of potential drawbacks. These drawbacks include:

* predisposition to late-stage stent thrombosis
* prevention of late vessel adaptive or expansive remodeling
* prevention of normal vasomotion and compliance
* hindrance to and sometimes a barrier for surgical revascularization
* Impairment of imaging with multi-slice CT

Additionally, as general coronary intervention procedures move towards treating
more diffuse disease, more stents are used in a single vessel. The use of
multiple stents within a single vessel often results in a vessel that has been
*paved* with stents. The paving of a vessel results in a situation by where it
is often difficult to perform future surgical bypass when prescribed; in some
cases, it is prohibited.

In an effort to continually improve outcomes in interventional cardiology
patient care, researchers are pursuing novel approaches to solve the drawbacks
described above while preserving the advances offered by current metallic
stents and DES. One such effort involves stenting coronary vessels with fully
bioresorbable scaffolds that act as *temporary* stents to support the vessel
during the initial critical months of healing and remodelling after dilation.
Such an approach can provide the benefits of metal stents * prevention of acute
vessel recoil and abrupt closure, and avoid the late negative consequences of
pathological remodelling of the vessel that may lead to late restenosis since
the bioresorbable stent is not permanent. In addition, if the bioresorbable
scaffold were drug-eluting, it could offer the additional benefit of a
traditional metallic DES by inhibiting neointimal hyperplasia.

Early efforts demonstrated:

* The use of polymer resorbable scaffolds is feasible * resorbable polymer
scaffolds have been successfully deployed in human patients.
* In most cases, deployment of the scaffold was accomplished using a
non-commercially viable, heated balloon catheter to expand the polymer scaffold
without stressing the bioresorbable material
* The use of *off-the-shelf* polymers may not be sufficient to address the
design requirements of a coronary scaffold. Optimization of polymer-based
coronary scaffolds may require a scaffold design and polymer materials
specifically engineered for vascular scaffold applications.
* Novel solutions are required to address the lack of visibility by X-ray with
these early materials, which is a standard clinical requirement for accurate
scaffold placement.

From the beginning, REVA Medical took a unique approach to fully integrate both
a novel material and a novel design in developing a REVA Sirolimus-Eluting
Bioresorbable Coronary Scaffold that provides the benefits of metal without the
permanency. The desired performance benefits include adequate strength, both at
the time of implantation and during the critical initial three month period of
vessel remodelling, scaffold expansion over the traditional (and expected)
expansion range of metal stents and x-ray visibility of the device.

A major drawback of contemporary polymers is that they lack intrinsic
radiopacity. An important advancement in the development of this polymer has
been the enhancement of x-ray visibility. Incorporation of iodine into the
polymer backbone allows the scaffold to be visualized using the angiographic
techniques that are currently used by physicians today.

The REVA Scaffold has been developed with two unique expansion designs. The
first design included a Slide and Lock expansion mechanism. Unlike traditional
deformable metal stent designs, the Slide & Lock design deploys by sliding open
and locking the scaffold into place. This novel scaffold design eliminates the
need to significantly deform the device during deployment. More recently, the
REVA scaffold has also been designed with a traditional deformable
configuration for expansion.

The purpose of the FANTOM II study is to evaluate a scaffold with a traditional
method of stent expansion of the REVA FANTOM Scaffold in a similar clinical
setting.

To evaluate the safety of a new scaffold platform in native coronary arteries
that includes incorporation of a deformable expansion technology and an
enhanced scaffold material that is a polycarbonate co-polymer of tyrosine
analogs. This will be accomplished through the implantation and evaluation of
the REVA FANTOM Sirolimus-Eluting Bioresorbable Coronary scaffold comprised of
Poly(I2DAT -co-lactic acid)

Prospective, multi-center, safety & performance study

Implantation of the REVA Sirolimus-Eluting Bioresorbable Coronary Scaffold.

Risks: possible side effects of the study procedure (see also question E9).

Burden: the scheduled visits at the study doctor (see also questions E3 and
E3a).