The Purpose of This Study is to Evaluate the Efficacy and the Safety of MDI-1228 Mesylate Gel Compared With Standard of Care Alone in Patients With Chronic Diabetic Foot Ulcers

Eligibility Criteria

• 1. Willing and able to participate and comply with all trial requirements and able to provide signed and dated informed consent prior to initiation of any trial procedures;
• 2. Male or female 18-75 years;
• 3. Meet diagnostic criteria for a diabetic ulcer with the presence of at least one target ulcer that meets the characteristics:
• * Located on dorsal or plantar surface of foot or below the knee.
• * Wagner grade 2, ulcerated lesion at or below the knee, without systemic infection.
• * The target ulcer should be the largest, and all each individual ulcers size should be less than 25cm2. All ulcers will be treated the same as the target ulcer.
• * Target ulcers persisted for at least 12 weeks prior to enrollment and have been on standard of care for at least 4 weeks prior to enrollment.
• * There is a minimum 3cm margin between the qualifying Target Ulcer and any other ulcers on the specified foot (post-debridement).
• 4. Subjects of child-bearing potential and their sexual partners do not plan to become pregnant within 3 months after the last dose of the investigational drug. Subjects must voluntarily use effective contraception. Male subjects must not plan to donate sperm.
• 5. Subjects must be willing to attend scheduled visits, follow study procedures and be able to provide written informed consent for the study.
• 6. History of documented Diabetes Mellitus (DM), Hb A1c should be lower than 12 or also can be within normal range due to control of DM from medications.
• 7. Subject has adequate vascular perfusion of the affected limb, confirmed by Ankle-Brachial Index (ABI) \>0.8 and \<1.3.
• 8. No active infection on all ulcers wound area by clinical inspection.
• 1. Allergy to the main components or excipients of MDI-1228_mesylate gel, allergy to JAK inhibitors (tofacitib, baricitinib, ruxolitinib), or individuals with allergic constitution.
• 2. Skin ulcers or chronic wounds caused by electroshock, chemicals, radioactive material etc.
• 3. The target ulcer has reduced in size by ≥30% in the last 4 weeks under standard treatment.
• 4. Those with cancerous ulcers or connective tissue diseases including lupus erythematosus, rheumatoid arthritis, scleroderma, etc.
• 5. The presence of a serious clinical infection, such as cellulitis, osteomyelitis, etc. or suspected malignant lesion at the site of the ulcerative lesion, or with other serious complications that may interfere with the healing of the ulcer/wound or affect the evaluation.
• 6. The ulcer site is accompanied by destruction of the joint capsule or bone, or there are sinus tracts that cannot be cleared by debridement.
• 7. Subjects on medications that are strong inhibitors of CYP2C8 and CYP3A4.
• 8. Leukocyte count \< 2×109/L or neutrophil \< 1×109/L or platelet count \<80x109/L or hemoglobin \< 90 g/L in screening period.
• 9. Albumin ALB \< 30 g/L in screening period.
• 10. ALT, AST \> 3 × ULN, total bilirubin TB \> 1.5 × ULN; serum creatinine Cr \> 2 × ULN in screening period.
• 11. Subject with uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg).
• 12. Subject with myocardial infarction, severe or unstable angina pectoris, class III or IV congestive heart failure defined by New York Heart Association (NYHA), or the presence of an arrhythmia clinically warranting intervention within 6 months prior to screening.
• 13. Acute complications of diabetes occurred within 6 months before screening, such as diabetic ketoacidosis, lactic acidosis, hyperosmolar hyperglycemic syndrome, or diabetic hyperosmolar coma.
• 14. Vascular reconstruction of the affected limb where the target ulcer is located within 3 months prior to screening.
• 15. Subject has participated in other clinical trials of new drugs or medical devices within 3 months prior to screening and used investigational drugs or medical devices.
• 16. Subject who has received a live vaccine within 1 month prior to the first dose or is scheduled to receive a live vaccine during the study period. The live vaccines include, but are not limited to measles, mumps, rubella, varicella, yellow fever, rabies, BCG, and typhoid vaccine etc.
• 17. Known active infections, e.g., bacterial, fungal, and viral infections, including human immunodeficiency virus infection (defined as HIV antibody positive), hepatitis B virus (HBV) infection \[defined as Hepatitis B surface antigen (HBsAg) positive and HBV-DNA ≥1000 cps/mL or 200 IU/mL\] and hepatitis C virus (HCV) infection (defined as anti-HCV antibody positive and HCV-RNA positive). Human Immunodeficiency Virus (HIV) positive patients could be eligible after discussion with medical monitor based on current status of HIV treatment.
• 18. Subject has used any immunosuppressant (e.g., systemic corticosteroids) within 4 weeks prior to screening; any topical steroids, topical antibiotics, or trauma biologics (e.g., cytokines) for the target wound within 2 weeks prior to screening; or any systemic or topical therapeutic medications or nutraceuticals (including herbal remedies) and treatments that may affect wound healing.
• 19. In the opinion of the investigator based on subject's medical history, the subject may have psychiatric condition (e.g., suicidal ideation), current or chronic drug abuse, that may pose a threat to the subject's adherence.
• 20. Pregnant or breastfeeding female patients.
• 21. In the opinion of the investigator, the subject has other conditions at the ulcer site that would otherwise make them unsuitable for participation in this study i.e visible skin diseases, sunburns, excessively deep tans, tattoos, scars etc.