Juvidex (Mannose-6-Phosphate) in Accelerating the Healing of Split Thickness Skin Graft Donor Sites
Condition: Wound
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The objective of this study is to compare the efficacy of two concentrations of Juvidex with
      placebo on the healing of split thickness skin graft donor sites
    

Detailed description: 
      Split thickness skin grafting is the transplantation of a patient's own cutaneous tissue
      harvested from an area of normal skin, to replace an area of skin loss or injury. The split
      thickness skin graft (SSG) is one of the most commonly performed operations in plastic and
      reconstructive surgery1. Indications for split skin grafting include: reconstruction after
      the surgical removal of cutaneous malignancies, to replace tissue lost in full-thickness
      burns and to cover chronic non-healing cutaneous ulcers. As with all grafting procedures, a
      donor site wound is created, and, in the case of SSGs, the wound is a partial-thickness wound
      that heals by re-epithelialisation. Often, the graft donor site is the slowest to heal, and
      it is the source of most of the postoperative discomfort. In patients who have sustained
      major burns affecting large percentages of their cutaneous surface area, early closure of
      burn wounds with autologous skin grafts can be limited by the lack of adequate donor sites.
      These donor sites may need to be re-harvested to provide further skin cover; however a delay
      of 2 to 3 weeks is often required to allow these sites to heal prior to re-harvesting.

      A treatment to accelerate the healing of SSG donor sites produced after harvest would address
      an area of high medical need, not only by providing an area available for re-harvest, but
      also by reducing the potential associated morbidities to the patient including pain and
      infection. This could also reduce length of hospital stay with associated reduced healthcare
      costs.

      Transforming growth factor betas (TGF-beta), are a naturally occurring protein which plays a
      central role in the wound healing response. Juvidex is being developed by Renovo as a
      therapeutic agent administered to accelerate the healing of acute wounds. The proposed
      mechanism of action is antagonistic and involves inhibiting the activation of TGF-beta 1 and
      TGF beta 2.

      Using healthy volunteers is an ideal way of studying the healing process on split thickness
      skin graft donor sites since the donor sites can be created so that they are exactly
      anatomically matched. These matched pairs can then be used to compare drug against placebo.

      The trial is being undertaken to assess the effects of intradermally injected and topically
      applied Juvidex on the healing of small skin graft donor sites in volunteer subjects. The
      trial will also compare the effects of a placebo treatment with standard care alone in the
      healing of the donor sites. This will enable any placebo effect to be accurately measured and
      allow an accurate assessment of actual drug effect.
    

Intervention name(s): Mannose-6-Phosphate (Juvidex); Mannose-6-Phosphate (Juvidex); Mannose-6-Phosphate (Juvidex); Mannose-6-Phophate (Juvidex); Placebo
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): 100µL of 300mM (8.46 mg/100μL) Juvidex will be injected intradermally into each cm2 of one 3cm2 donor site and into the 0.5cm border around the donor site no more than 20 minutes before graft harvest (total dose 750µL). A further 300µL of 300mM (8.46 mg/100μL) Juvidex will be applied topically within 30 minutes of graft harvest and 24 hours after graft harvest.
100µL of placebo will be injected intradermally into each cm2 of the other 3cm2 donor site and into the 0.5cm border around the donor site no more than 20 minutes before graft harvest (total dose 750µL). A further 300µL of placebo will be applied topically within 30 minutes of graft harvest and 24 hours after graft harvest.; 100µL of 600mM(16.93 mg/100μL) Juvidex will be injected intradermally into each cm2 of one 3cm2 donor site and into the 0.5cm border around the donor site no more than 20 minutes before graft harvest (total dose 750µL). A further 300µL of 600mM (16.93 mg/100μL) Juvidex will be applied topically within 30 minutes of graft harvest and 24 hours after graft harvest.
100µL of placebo will be injected intradermally into each cm2 of the other 3cm2 donor site and into the 0.5cm border around the donor site no more than 20 minutes before graft harvest (total dose 750µL). A further 300µL of placebo will be applied topically within 30 minutes of graft harvest and 24 hours after graft harvest.; 300µL of 300mM (8.46 mg/100μL) Juvidex will be applied topically to one 3cm2 donor site within 30 minutes of graft harvest and 24 hours after graft harvest.
300µL of placebo will be applied topically to the other 3cm2 donor site within 30 minutes of graft harvest and 24 hours after graft harvest.; 300µL of 600mM (16.93 mg/100μL) Juvidex will be applied topically to one 3cm2 donor site within 30 minutes of graft harvest and 24 hours after graft harvest.
300µL of placebo will be applied topically to the other 3cm2 donor site within 30 minutes of graft harvest and 24 hours after graft harvest.; 100µL of placebo will be injected intradermally into each cm2 of one 3cm2 donor site and into the 0.5cm border around the donor site no more than 20 minutes before graft harvest (total dose 750µL). A further 300µL of placebo will be applied topically within 30 minutes of graft harvest and 24 hours after graft harvest.
Standard Care (moist wound healing dressings alone) will be applied to the other 3cm2 donor site.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Double blind; Placebo controlled; wound healing