Clinical Trial to Evaluate Blister Graft Utilizing a Novel Harvesting Device for Treatment of Venous Leg Ulcers

This study is a multi-center, randomized, controlled open-label study designed to evaluate
the safety and effectiveness of epidermal grafting using the CelluTome® system plus
multi-layer compression therapy versus multi-layer compression (SOC) in the treatment of
venous leg ulcers.

The study will have two phases: Screening and Treatment. The Screening Phase (1 -14 days) is
designed to determine whether subjects are eligible to proceed to the Treatment Phase of the
study and consists of a series of screening assessments designed to determine eligibility.

At or up to 14 days before the first Screening Phase Visit (S1), written informed consent
from the subject will be obtained by the Investigator or suitably qualified designee before
the performance of any other protocol-specific procedure.

At the first Screening Phase Visit (S1), the Investigator will select the study (target)
ulcer. Each subject will have only one VLU selected as the study (target) ulcer. In the
situation where a subject has more than one VLU at the S1 visit, the Investigator will select
the largest VLU that meets the eligibility criteria of the protocol as the study (target)
ulcer.

Patients whose target ulcer has been treated with compression therapy for the previous two
weeks are eligible to enter the treatment phase once all of the inclusion and exclusion
criteria are met. If the ulcer has not received compression, the patient should be placed in
compression and enrolled in the study after 14 days of compression therapy. Ulcers that have
decreased in size by more than 40% during the screening period will be excluded as "rapid
healer." Subjects that meet the inclusion/exclusion criteria at the end of screening will be
randomized to either the Cellutome graft plus Standard of Care group or just the Standard of
Care group. At Treatment Visit 7, subjects in the Standard of Care group that have healed
<40% will be allowed to cross over to the Cellutome graft group.

The study will consist of up to 30 centers in the United States each contributing about 10
subjects per center in order to obtain 194 evaluable subjects. The investigators anticipate a
10% drop out rate during the trial therefore a total of 213 subjects will be recruited. This
trial employs an adaptive design therefore the enrollment numbers may be reduced or increased
based on planned interim analysis.

Inclusion Criteria:

1. At least 18 years old.

2. Adequate arterial flow (Ankle Brachial Pressure Index (ABI) > 0.75. (Calculations will
be made using measurements from both posterior tibial and dorsalis pedis arteries as
well as both arms), OR Skin Perfusion Pressure (SPP) >30, OR biphasic PVR OR TBI >
0.60 OR TCPO2 > 30mmHg OR adequate perfusion as demonstrated on florescent
angiography, LUNA®).

3. Presence of a venous leg ulcer through full skin thickness but not down to muscle,
tendon or bone. The largest ulcer will be the index ulcer and the only one included in
the study. If other ulcerations are present on the same leg they have to be more than
2 cm apart from the index ulcer.

4. Study ulcer has been present for at least one month prior to the initial screening
visit, and is excluded if it has undergone 12 months of continuous high strength
compression therapy over its duration.

5. Study ulcer is a minimum of 2.0 cm2 / maximum of 25 cm2 at the randomization visit.

6. The target ulcer has been treated with compression therapy for at least 14 days prior
to randomization.

7. Ulcer has a clean, granulating base with minimal adherent slough at the randomization
visit.

8. Patient understands / is willing to participate in the clinical study and can comply
with weekly visits and follow-up regimen.

9. Patient has read and signed the IRB/IEC approved Informed Consent Form before
screening procedures are undertaken.

Exclusion Criteria:

Potential subjects meeting any of the following criteria will be excluded from enrollment
and subsequent randomization.

1. Study ulcer(s) deemed by the investigator to be caused by a medical condition other
than venous insufficiency. These may include, but are not limited to: fungal
ulcerations, malignant ulcerations, and ulcerations due to arterial insufficiency.

2. Study ulcer exhibits clinical signs and symptoms of infection at the SV (screening
visit) or TV1 (Treatment Visit 1).

3. Known allergy to the components of the multi-layer compression bandaging, or who
cannot tolerate multi-layer compression therapy.

4. Study ulcer is suspicious for cancer should undergo an ulcer biopsy to rule out a
carcinoma of the ulcer. The patient may be enrolled after a negative biopsy.

5. Patients with a history of more than two weeks treatment with immunosuppressants
(including systemic corticosteroids), cytotoxic chemotherapy, or application of
topical steroids to the ulcer surface within one month prior to initial screening, or
who receive such medications during the screening period, or who are anticipated to
require such medications during the course of the study.

6. Study ulcer has been previously treated with tissue engineered materials (e.g.
Apligraf® or Dermagraft®) or other scaffold materials (e.g. Oasis, meristem) within
the last 30 days

7. Study ulcer requiring negative pressure wound therapy or hyperbaric oxygen during the
course of the trial.

8. Ulcers on the dorsum of the foot or with more than 50% of the ulcer below the
malleolus are excluded.

9. Pregnant or breast feeding.

10. Known history of having Acquired Immunodeficiency Syndrome (AIDS) or with a history of
Human Immunodeficiency Virus (HIV).

11. Known uncontrolled Diabetes Mellitus, as measured by an HbA1c > 10%.

12. Ulcers that have healed more than 40% during the screening phase are excluded.

13. Patients on any investigational drug(s) or therapeutic device(s) within 30 days
preceding screening (i.e. S1); or patient or physician anticipates use of any of these
therapies by the subject during the course of the study.

14. History of radiation at ulcer site.

15. Presence of one or more medical conditions, including renal, hepatic, hematologic,
active auto-immune or immune diseases that, would make the subject an inappropriate
candidate for this ulcer healing study.

16. Patients who are unable to understand the aims and objectives of the trial.

17. Presence of any condition(s) which seriously compromises the subject's ability to
complete this study, or has a known history of poor adherence with medical treatment.