Resorbable Glass Fiber Matrix in the Treatment of Diabetic Foot Ulcers

This study is a prospective, multi-center, RCT designed to collect patient outcome data on
two commercially available SOC treatments for DFUs. The trial will be single blinded in
regard to wound healing assessment (another clinician, other than the investigator at each
site will assess wound healing) and confirmation of wound healing will be overseen by an
independent adjudication committee made up of wound care experts. The study will last twelve
weeks, with a two week screening period prior to enrollment.

There are two standard of care arms in the study:

Arm 1: The SOC therapy in this study is offloading of the DFU (CAM boots or total contact
casting [TCC] if the subject's foot is too large for a CAM), appropriate sharp or surgical
debridement, infection management (systemic antibiotics only in conjunction with debridement)
and wound care covering with bioactive resorbable glass fiber dressing, MIRRAGEN™Advanced
Wound Matrix, followed by a padded 3-layer dressing comprised of 4x4 gauze pads, soft roll
and compressive wrap (DynaflexTM or equivalent).

Arm 2: The SOC therapy in this study is offloading of the DFU (CAM boots or total contact
casting [TCC] if the subject's foot is too large for a CAM), appropriate sharp or surgical
debridement, infection management (systemic antibiotics only in conjunction with debridement)
and wound care covering with calcium alginate Fibracol dressing followed by a padded 3-layer
dressing comprised of 4x4 gauze pads, soft roll and compressive wrap (DynaflexTM or
equivalent).

Inclusion Criteria:

- At least 18 years old.

- Presence of a DFU, Wagner 1 (see Appendix B for definitions), extending at least
through the dermis provided it is below the medial aspect of the malleolus.

- The index ulcer will be the largest ulcer if two or more DFUs are present with the
same Wagner grade and will be the only one evaluated in the study. If other
ulcerations are present on the same foot they must be more than 2 cm distant from the
index ulcer.

- Index ulcer (i.e. current episode of ulceration) has been present for greater than 4
weeks prior to SV1 and less than 1-year, as of the date the subject consents for
study.

- Index ulcer is a minimum of 1.0 cm2 and a maximum of 25 cm2 at SV1 and TV1.

- Adequate circulation to the affected foot as documented by a dorsal transcutaneous
oxygen measurement (TCOM) or a skin perfusion pressure (SPP) measurement of ≥ 30 mmHg,
or an Ankle Branchial Index (ABI) between 0.7 and 1.3 within 3 months of SV1, using
the affected study extremity. As an alternative arterial Doppler ultrasound can be
performed evaluating for biphasic dorsalis pedis and posterior tibial vessels at the
level of the ankle or a Toe Brachial Index (TBI) of > 0.6 is acceptable.

- The target ulcer has been offloaded for at least 14 days prior to randomization.

- Females of childbearing potential must be willing to use acceptable methods of
contraception (birth control pills, barriers or abstinence) during the course of the
study and undergo pregnancy tests.

- Subject understands and is willing to participate in the clinical study and can comply
with weekly visits.

Exclusion Criteria:

- Index ulcer(s) deemed by the investigator to be caused by a medical condition other
than diabetes.

- Index ulcer, in the opinion of the investigator, is suspicious for cancer and should
undergo an ulcer biopsy to rule out a carcinoma of the ulcer.

- Subjects with a history of more than two weeks treatment with immune-suppressants
(including systemic corticosteroids >10mg daily dose), cytotoxic chemotherapy, or
application of topical steroids to the ulcer surface within 1-month prior to first
SV1, or who receive such medications during the screening period or who are
anticipated to require such medications during the course of the study.

- Subjects taking a selective COX-2 inhibitor, such as Celecoxib, for any condition.

- Subjects on any investigational drug(s) or therapeutic device(s) within 30 days
preceding SV1.

- History of radiation at the ulcer site (regardless of time since last radiation
treatment).

- Index ulcer has been previously treated or will need to be treated with any prohibited
therapies. (See Section 7.3 of this protocol for a list of prohibited medications and
therapies).

- 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.

- Osteomyelitis or bone infection of the affected foot as verified by x-ray within 30
days prior to randomization. (In the event of an ambiguous diagnosis, the Principal
Investigator will make the final decision).

- Subject is pregnant or breast-feeding.

- Presence of diabetes with poor metabolic control as documented with an HbA1c > 12.0
within 90 days of randomization.

- Subjects with end stage renal disease as evidenced by a serum creatinine ≥ 3.0 mg/dL
within 6 months of randomization.

- Index ulcer has reduced in area by 20% or more after 14 days of SOC from SV1 to the
TV1/randomization visit.