A Dose Finding Study of Topically Applied I-020201 as an Adjunct to Good Standard-of-care in Patients With Chronic Diabetic Foot Ulcers (DFU)

• Incidence of complete wound closure (full re-epithelialization with confirmation 4 weeks afterwards) [ Time Frame: At 12 and 16 weeks after treatment start ] [ Designated as safety issue: No ]
• Incidence of complete wound closure (full re-epithelialization with confirmation 4 weeks afterwards) [ Time Frame: Within the whole study period (28 weeks after treatment start) ] [ Designated as safety issue: No ]
• Time to complete wound closure (full re-epithelialization with confirmation 4 weeks afterwards). [ Time Frame: At any time during the study ] [ Designated as safety issue: No ]
• Incidence of treatment failure defined as <30% decrease in ulcer size [ Time Frame: After 8 weeks of treatment ] [ Designated as safety issue: No ]
• Incidence of patients with ulcer recurrence [ Time Frame: Up to 16 and 28 weeks after treatment start ] [ Designated as safety issue: No ]
• Incidence of treatment-related adverse events (systemic and at the target ulcer) and all AEs/SAEs [ Time Frame: During the whole study period ] [ Designated as safety issue: No ]
• Changes in systemic PDGF-AB and antibody levels against TG-PDGF.AB and aprotinin [ Time Frame: At 1, 4, 12, 16 and 20 weeks after treatment start ] [ Designated as safety issue: No ]
• Changes in vital signs, body weight, physical examination and laboratory parameters [ Time Frame: Throughout the study and 28 weeks after treatment start ] [ Designated as safety issue: No ]

Although major improvements in the management and treatment of diabetic foot ulcers have been made, the clinical and financial burden of such long-term wounds is still high and is likely to increase as the general population ages. The large population affected by diabetic foot ulcers and the high rates of failure ending with amputation even with the best therapeutic regimens have resulted in the development of new therapies. I-020201 is a bioactive therapy intended for topical treatment of hard-to-heal diabetic foot ulcers, stimulating the granulation tissue formation. This study aims to evaluate the safety and efficacy of I-020201 in adjunct to good standard of care in patients with chronic diabetic foot ulcer.

• Procedure: Good Standard of Care (GSoC)
  Procedural treatment twice per week
• Biological: Vehicle
  Topical fibrin as an adjunct to GSoC twice per week
• Biological: I-020201
  Topical treatment with 3 different concentrations as an adjunct to GSoC twice per week

• Experimental: Good Standard of Care (GSoC)
  Twice per week
  Intervention: Procedure: Good Standard of Care (GSoC)
• Experimental: GSoC + vehicle
  Twice per week
  Interventions:

  • Procedure: Good Standard of Care (GSoC)
  • Biological: Vehicle
• Experimental: GSoC + I-020201 (33microg)
  Twice per week
  Interventions:

  • Procedure: Good Standard of Care (GSoC)
  • Biological: I-020201
• Experimental: GSoC + I-020201 (100microg)
  Twice per week
  Interventions:

  • Procedure: Good Standard of Care (GSoC)
  • Biological: I-020201
• Experimental: GSoC + I-020201 (300microg)
  Twice per week
  Interventions:

  • Procedure: Good Standard of Care (GSoC)
  • Biological: I-020201

Inclusion Criteria:

• male or female, aged ≥ 18 years
• given written informed consent
• female of childbearing potential with a negative result from the pregnancy test at screening who agrees to use an acceptable birth control method (hormonal or IUD) or abstinence throughout the trial
• Type 1 or Type 2 Diabetes mellitus with HbA1c =< 12%
• with only one diabetic foot ulcer on the foot to be treated on or below the ankle

Exclusion Criteria:

• pregnant or breast-feeding
• known or suspected allergies to any of the components of the I-020201
• uncontrolled anemia (Hb < 9 g/dL in females and < 10 g/dL in males)
• hypoalbuminemia (albumin < 3 g/dL)
• overtly infected target ulcer (as judged by investigator)
• highly exuding wounds (wounds that require a daily dressing change)
• osteomyelitis
• systemic infections
• acute Charcot foot and severe chronic Charcot deformity
• ABPI < 0.7 or ankle systolic pressure < 70 mm Hg

• one of the following findings (only 1 out of 3 tests is required):

  • on Doppler waveform analysis on the dorsalis pedis and posterior tibial arteries a monophasic or biphasic flow (with loss of reverse flow) in either foot artery, or
  • a toe: brachial index < 0.7, or
  • transcutaneous oxygen pressure (TcpO2) < 40 mm Hg
• suspicion, presence or history of systemic or local cancer or tumor of any kind