Feasibility, Multi-center prospective study of Check-Cap's P1 Capsule System in Patients eligible for CRC screening

Check-Cap is an R&D stage company which is engaged in the development and
commercialization of a miniaturized, ingestible disposable device for the
screening of CRC market. The imaging is based on two modalities: a Compton
backscattering Imaging and X-Ray technology
CRC -Colorectal cancer is the second leading cause of cancer death but is
largely preventable. Current strategies to prevent colorectal cancer vary
considerably with regard to effectiveness, up-front costs, risks, and
invasiveness. Current levels of participation in colorectal cancer screening in
the U.S. and Europe population are low. Both physician and patient attitudes
contribute to low levels of screening uptake. New colorectal cancer tests are
one mechanism to improve adherence.
Studies published in the early 1990s, showing that screening for colorectal
cancer can reduce colorectal cancer-related mortality, led many organizations
to recommend screening in asymptomatic, average-risk adults older than 50
years. Since then, however, national screening rates remain low in most
countries. Several important studies published over the past four years have
refined our understanding of existing screening tools and explored novel means
of screening and prevention
In an attempt to reduce this cancer related death, legislation was passed in
both the US and Germany in 2002, which establishes by law, reimbursement for
screening colonoscopy in the population 50 years and older in the US, and 55
and older in Germany. This has increased the potential number of screening
colonoscopies in these 2 countries alone to 15 million colonoscopies a year
Screening of the colon is performed by various modalities: FOBT, FIT,
Sigmoidoscopy, endoscopic colonoscopy and virtual colonoscopy. These tests are
invasive and require as well the cleansing of the colon. Most patients object
the rigorous preparation required for cleansing of the colon. It is regarded
as one of the main objections of patients to comply with the screening
guidelines. The only way to bridge the gap between the number of colonoscopies
presently performed and the potential market, is by way of a technological
breakthrough that will replace the cumbersome flexible colonoscope presently
used for screening colonoscopy. Check-Cap Ltd believes that the device which
it is developing may be just the answer needed to solve this public health
issue.
1.1. Technology
The proposed device is designed to be ingested without any cleansing of the
colon and will travel through the GI tract naturally while the patient
continues eating normally. The technology of the P1 Capsule System is based on
a low dose radioactive [RA] sealed source embedded in the capsule which
radiates through a collimator to all directions. The capsule*s outer surface
is covered by detectors which are designed to count the backscattered particles
in a gamma energy spectrum. The capsule is designed to start scanning once it
reaches the ceacum and the radiation is emitted only when the capsule is
propagating along the colon during contraction of the walls. While stationary
(which is most of the time) the capsule is set at an idle mode and the RA
radiation is blocked by the collimator. The transit time of the capsule in the
colon might vary from 24-100 hours, depending the typical bowel activity of the
patient.


More details on the technology, capsule design, its structure and operation are
presented in App. IIX

Check-Cap*s P1 Capsule System is an innovative disposable medical device that
will enable a patient friendly, painless, private and accurate procedure for
colorectal cancer screening.
For the screening procedure, the patient swallows a capsule and can then go
about his or her normal daily routine. The capsule travels painlessly through
the gastrointestinal tract, seeking polyps, the precursors of colorectal
cancer. In order to increase the contrast of the colon*s walls and to
differentiate them from their content, it is essential to increase the stool*s
contrast by ingesting radio-opaque material. It is a standard procedure using
approved Iodine based liquids (Telebrix or Gastrographine) or Barium sulphate
Tagitol) at the discretion of the hospital similar to the preparation to
abdominal CT.

During the passage of the capsule in the gastrointestinal tract, it transmits
information to a worn recorder. After the capsule is expelled, the data from
the recorder is downloaded to an acquisition workstation. Later, the data is
transferred to a processing workstation where dedicated software visualizes and
analyses the data. At the end of the procedure and after a colonoscopy, the
patient will proceed following the standard procedure.

To establish the safety and preliminary efficacy of Check-Cap*s P1 Capsule
System in patients eligible for CRC screening

Study design -
In order to get statistically significant results, patients will be recruited
among those who were diagnosed with significant polyps by Virtual Colonoscopy
(or diagnostic colonoscopy).
According to the definition in the literature of Virtual Colonoscopy studies -
*significant* polyp, relates to polyps size of 10+ mm. Such population
enrichment will introduce many more polyps into the study as compared to ~25%
incidence of polyps in normal population and only 6-10% of significant ones (10
mm and up).
According to clinical guidelines, patients diagnosed with polyps using Virtual
Colonoscopy are referred to polypectomy. In the proposed protocol, eligible
patients will be evaluated by the P1 Capsule System and by FOBT before the
therapeutic Colonoscopy procedure

• Colon perforation which lead to contamination of the abdominal cavity
• Retention of capsule for extended periods (>300 hours) while patient is not
constipated
• Significant abdominal pain that requires medical attention.