Lower Limb Ulcers With Diabetes Mellitus

Primary Objective: To assess the safety profile of TWB-103 administered to subjects with diabetic lower limb ulcers Secondary Objective: To explore the efficacy of TWB-103 administered to subjects with diabetic lower limb ulcers

TWB-103

Human fetal dermal fibroblasts

gel

5

Primary Outcome Measures :
Incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Day 1~ Day 169 ]
Pre-existing abnormalities are considered as AE or SAE only when the conditions escalate. The following events should be discussed specifically:

Study wound and its periphery: Infection, pain, pruritus/irritation, skin dysfunction/blister, osteomyelitis, cellulitis, edema/swelling and unexpected surgery
Non-study area and systemic: Infection, pain, pruritus/irritation, skin dysfunction/blister, osteomyelitis, cellulitis, edema/swelling, unexpected surgery, accidental injury, abnormal lab test and general disorders


Secondary Outcome Measures :
The percentage of subjects with confirmed study wound closure at each week up to 12 weeks [ Time Frame: Day 1~Day 85 ]
* Wound closure is defined as "full epithelialization of the wound with the absence of drainage and without sign of abscess under the epithelium". An ulcer is considered healed only after wound closure is re-confirmed at the visit 2 weeks later

Time (days) to confirmed wound closure for those subjects whose wounds are healed during treatment period and during the study period. [ Time Frame: Day 1~Day 85 ]
* Wound closure is defined as "full epithelialization of the wound with the absence of drainage and without sign of abscess under the epithelium". An ulcer is considered healed only after wound closure is re-confirmed at the visit 2 weeks later

Reduction of individual wound area for up to 12 weeks [ Time Frame: Day 1~ Day 85 ]
Reduction of wound area at each week up to 12 weeks. [ Time Frame: Day 1~ Day 85 ]
General granulation rate [ Time Frame: Day 1~Day 169 ]
Granulation rate will be recorded by comments from the investigator. Images before and after excision should be recorded.

Quality of granulation [ Time Frame: Day 1~Day 169 ]
Quality of granulation tissue will be recorded by comments from the investigator, including the color and tissue status. Images before and after excision should be recorded.

Reduction of wound volume for individual subject measured by 3D camera and analysis software up to 12 weeks [ Time Frame: Day 1~Day 169 ]
(only for those subjects who have received the 3D measurement)

Inclusion Criteria:

Adults at least 20 years of age.
With diagnosed diabetic mellitus (DM), e.g. currently under DM medication treatment, or with HbA1c ≧6.5% but < 12%, or with fasting plasma glucose ≧126 mg/dL (7.0 mmol/L), or with plasma glucose ≧ 200 mg/dL (11.1 mmol/L) in the two-hour 75-gram oral glucose tolerance test (OGTT).
With at least one cutaneous ulcer on the foot or the lower legs, and not healing for at least 4 weeks (the ≧2-week standard of care period can be counted as part of the 4-week ulcer history).
With ankle brachial index (ABI) ≥ 0.4 on the limb with the study ulcer. For subjects with 0.6>ABI ≧0.4, the investigator will arrange for providing proper treatment to the subject, such as improving circulation by medication or surgical procedures, etc.
The study wound is not prone to infection.
The wound should allow complete sealing of the wound by TegadermTM film.
The study wound size is between 1~33 cm2. The depth of wound may reach ligament, joint capsule, fascia, or tendon. There should be no sign of osteomyelitis. The wound does not exceed Wagner Grade 27.
Under the standard care of Investigator for at least 2 weeks, the study wound has not shown significant healing. Significant healing is defined as the following: The area of healed tissue reaches at least 30% of the area of initially presented wound.
When the subject has more than one wound which met the inclusion criteria, only one wound is selected as the study wound. The other wounds will be treated by standard cares.
Co-morbidities are under control and non-life threatening as determined by the Investigator based on medical history, physical examination, vital signs, or clinical laboratory tests, etc.
A negative pregnancy test at Screening. This applies to any female subject with childbearing potential.
Agrees to use acceptable contraceptive methods while on study (from signing informed consent form to the end of the study). This applies to any female subject with childbearing potential and any male subject whose female partner has childbearing potential.

Acceptable contraceptive methods include:

Established use of oral, injected or implanted hormonal methods of contraception
Placement of an intrauterine device (IUD) or intrauterine system (IUS)
Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps)
Able to follow the Investigator's instruction on wound care.
With signed informed consent form.

Exclusion Criteria:

Being pregnant or nursing.
With autoimmune disease other than diabetes, e.g. lupus erythematosus, multiple sclerosis.
With current malignancy or hypo-immunity.
With history of recurrent cancer, metastatic cancer, cancer which has high probability of metastasis, or cancer on the limb where the study wound is located.
With serum chemistry abnormalities below

AST or ALT > 5 × ULN,
Serum albumin < 2.0 g/dL,
With history of HIV infection
With history of alcoholism or drug abuse.
Received any cell-based product at the study wound.
Received an investigational drug, device or biological/bioactive treatment within 30 days prior to Screening Visit.
With any clinical condition or significant concurrent disease judged by the investigator to complicate the evaluation of the trial treatment.
With history of sensitivity to materials of bovine, porcine origin, or human serum albumin.
With active infection or active osteomyelitis in the study wound.