Clinical Study to Evaluate Efficacy and Safety of ALLO-ASC-DFU in Patients With Diabetic Wagner Grade 2 Foot Ulcers.

Study Overview
=================
Brief Summary
-----------------
This is a phase III double-blind study to evaluate the efficacy and safety of ALLO-ASC-DFU in patients with Diabetic Wagner grade 2 Foot Ulcer, compared to placebo therapy.

Detailed Description
-----------------
Experimental: ALLO-ASC-DFU, Placebo Comparator: Vehicle Sheet, Study type: Interventional, Study design: Randomized, Placebo-controlled, Double blind, Parallel-group, Multi-center Study

Official Title
-----------------
Phase 3 Clinical Study to Evaluate Efficacy and Safety of ALLO-ASC-DFU in Patients With Diabetic Wagner Grade 2 Foot Ulcers: A Randomized, Comparator-controlled, Double-blind, Parallel-group, Multi-center Study

Conditions
-----------------
Diabetic Foot Ulcer

Intervention / Treatment
-----------------
* Biological: ALLO-ASC-DFU
* Procedure: Vehicle Sheet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is between 19 and 75 years of age. Subject is diagnosed with Type I or Type II diabetics. Diabetic foot ulcer has been more than 4 weeks but less than 52 weeks at the screening visit. Ulcer located in the foot and ulcer size is between 1.5 15 cm2. Ulcer graded 2 by Wagner grade. Foot ulcer extended to ligament, tendon, joint capsule, fascia, muscle and periosteum. Ulcer is free of necrotic debris. Ulcer area blood circulation meets one of the following criteria; Blood vessels around the ulcer detected by Doppler Test Range of Ankle Brachial Index (ABI) is > 0.7 to < 1.3 Transcutaneous Oxygen Pressure (TcPO2) > 30mmHg or Toe Blood Pressure (TBP) > 40mmHg. Skin Perfusion Pressure (SPP) > 30mmHg Subject is able to give written informed consent prior to study start and willing to comply with the study requirements. Exclusion Criteria: Ulcer is of non-diabetic pathophysiology. There is gangrene in any part of the target foot ulcer. The longest dimension of the target foot ulcer exceeds 15 cm at the enrollment visit. Other wounds within 2cm of the target foot ulcer. The ulcer has increased or decreased in size by ≥ 30% during two weeks after the screening visit. Patient requiring intravenous (IV) antibiotics to treat foot wound infection at the screening and enrollment visit. Current evidence of active charcot on the study foot, osteomyelitis, cellulitis, or evidence of other infection including fever or purulent drainage from wound site. Patient with skin lesion confirmed by biopsy (when Investigator deems suspicious) and then judged by Investigator to be an etiology other than diabetic foot ulcer. An active malignant tumor(malignant melanoma, squamous cell carcinoma, basal cell carcinoma) on the body or skin. Have a glycated hemoglobin A1c (HbA1c) level of > 14% Have random blood sugar > 450mg/dL Have severe renal failure with creatinine > 3.0mg/dL. Have severe hepatic deficiencies Total bilirubin ≥ 1.5×upper normal limit(UNL) AST, ALT ≥ 2.0×UNL Serum albumin < 2.0mg/dL Is Human Immunodeficiency Virus (HIV) positive Have a known history of allergic or hypersensitive reaction to bovine-derived proteins or fibrin glue Pregnant or breast-feeding. Is unwilling to use an acceptable method of birth control during the whole study. Have a clinically relevant history of alcohol or drugs abuse at the screening visit. Is not able to understand the objective of the study or to comply with the study requirements Is considered by the Investigator to have a significant disease which might impact the study Is considered not suitable for the study by Investigator Have a history of malignancy within the last 5 years (except carcinoma in situ) Is currently or were enrolled in another clinical study within 60 days of screening Have undergone wound treatments with growth factors, dermal substitutes, or other biological therapies within the last 30 days. Is receiving oral or parenteral corticosteroids, any immunosuppressive, or cytotoxic agents with unstable dose within the last 30 days Cannot maintain off-loading process and device.

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALLO-ASC-DFU<br>Hydrogel sheet containing allogenic adipose-derived mesenchymal stem cells | Biological: ALLO-ASC-DFU<br>* Application of ALLO-ASC-DFU sheet to Diabetic Wagner grade 2 Foot Ulcer<br>|
| Placebo Comparator: Vehicle sheet<br>Hydrogel sheet without allogenic mesenchymal stem cell | Procedure: Vehicle Sheet<br>* Application of Vehicle sheet to Diabetic Wagner grade 2 Foot Ulcer<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportions of subjects who achieved complete wound closure |  | During 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time taken to complete wound closure |  | During 12 weeks | 
| Proportions of subjects who achieved complete wound closure at every visit |  | During 12 weeks | 
| Change rates in wound size and depth compared to baseline groups |  | During 12 weeks |