A Study to Evaluate Safety and Efficacy of APO-2 at Three Different Doses in Patients With Diabetic Foot Ulcer
Condition: Diabetic Foot Ulcer (DFU)
MeSH terms: Diabetic Foot; Foot Ulcer; Ulcer
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The MARSYAS II study which will be conducted in patients with diabetic foot ulcer (DFU)
      consists of a Lead-In Phase for safety assessment of multiple doses of the biologic
      investigational medicinal product (IMP) APO-2 and of a Main Phase (Phase II Study) to assess
      the efficacy and safety of the IMP. The phase II study will be a randomized study at multiple
      clinical centers and it will be double-blind meaning that neither the investigator nor the
      treated patient know if the IMP or a placebo is applied; the study will investigate the
      safety and clinical efficacy of multiple dose administrations at three dose levels of APO-2
      (low dose, medium dose or high dose) compared with placebo.
    

Detailed description: 
      APOSEC is a secretome released by cultured, stressed peripheral blood mononuclear cells
      (PBMC) in medium. Content analysis revealed that APOSEC harbors a myriad of proteins,
      exosomes, lipids, phospholipids, cholesterols as well as antimicrobial peptides. It was shown
      that the topical application of APOSEC mixed with a hydrogel, called APO-2, promotes/enhances
      wound healing.

      The MARSYAS II main study will be a multinational, multicenter, randomized, double-blind,
      placebo-controlled, parallel group, dose-ranging phase II study to investigate the safety and
      clinical efficacy of multiple dose administrations at three dose levels of APO-2 compared
      with placebo in patients with diabetic foot ulcer (DFU).

      The main study will be preceded by a safety lead-in period evaluating multiple dose safety
      (25 U/ml APO-2) in patients with DFU in a cohort of 12 patients randomized at a ratio of 3:1
      between APO-2 and placebo at 2 to 4 study sites. The minimum duration of an individual
      patient in the safety lead-in period is 93 days (including screening), with a maximum of
      approximately 117 days.

      In the main study 120 eligible patients will be randomized at a ratio of 1:1:1:1 between
      APO-2 (three doses) and placebo. Patients will be stratified by wound size (at least 20% of
      patients will need to have wound size > 4 square cm), and randomly assigned to 1 of 4
      treatment groups (low dose [12.5 U/ml], medium dose [25 U/ml], high dose [50 U/ml] or
      placebo). After randomization, patients will receive IMP three times per week during the
      4-week active treatment period. 0.5 ml IMP will be applied per square cm wound surface area
      for each dose group.
    

Intervention name(s): APO-2; Placebo
Intervention type(s): Biological; Other
Intervention description(s): APO-2: dose adjusted gel for topical administration.; Placebo gel for topical administration.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: During Safety Lead In Phase 12 patients will be randomized to one of two study arms at a ratio of 3:1 between APO-2 and placebo.
During the Main Phase 108 patients will be randomized to one of the four study arms at a ratio of 1:1:1:1 between APO-2 (three doses) and placebo.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment