Preliminary Testing of New Treatment for Chronic Leg Wounds
Condition: Varicose Ulcer
MeSH terms: Varicose Ulcer; Ulcer
Study type: Interventional
Phase: Phase 1

Summary: 
      Most chronic (long-lasting) wounds of the leg (also known as venous ulcers) fail to heal in a
      reasonable period of time. Although researchers have made great progress in understanding how
      the body repairs wounds, attempts to develop new treatments have been disappointing. In
      general, treatments based on recent findings about the details of wound repair have not
      greatly reduced the number of people who have chronic wounds. The long-term goal of this
      study is to evaluate a new approach for healing a chronic wound. Current methods of directly
      applying substances that are involved in wound healing to a chronic wound do not cause enough
      healing. PDGF-B (platelet-derived growth factor B), a factor associated with wound healing,
      might dramatically enhance healing if a genetically engineered virus is injected into the
      wound that causes cells in the wound to produce PDGF-B in large quantities.
    

Detailed description: 
      Most chronic wounds of the leg fail to heal in a reasonable period of time. In fact, despite
      considerable advances in elucidating the molecular basis of wound repair, attempts to develop
      new therapies have been disappointing. In general, therapies based on recently elucidated
      mechanisms of wound repair have had minimal effect on the overall number of individuals with
      a treated healed chronic wound. The long-term goal of this study is to evaluate a new
      approach for healing a chronic wound. Current methods of applying cytokines as a topical
      protein to treat chronic wounds result in an inadequate response. PDGF-B, a growth factor
      associated with wound healing, might dramatically enhance wound healing when produced in
      large quantities in the wound bed via adenovirus-mediated gene overexpression by the cells of
      the wound bed.

      This study consists of two trials. The goal of Trial A, a dose-escalation trial, is to
      determine the maximum tolerated dose (MTD) of PDGF-B/Ad5, an adenovirus vector designed to
      overexpress PDGF-B, with respect to local and systemic toxicity and biologic feasibility. The
      primary objective is to evaluate the acute safety, both local and systemic, of an intra-ulcer
      injection of PDGF-B/Ad5, thereby determining the recommended dose. Upon evaluating patients,
      they will be treated with a single intra-ulcer injection of PDGF-B/Ad5 in the wound. Patients
      will receive only one dose, which will be administered during a 72-hour inpatient stay in a
      research unit at the Hospital of the University of Pennsylvania.

      This study will use a standard three-six dose-escalation scheme. The MTD is defined as the
      highest dose for which fewer than two of six subjects experience a severe adverse reaction.
      Each patient will be closely monitored for clinical adverse reactions resulting from
      treatment with PDGF-B/Ad5. Toxicity will be graded according to the National Cancer
      Institute's Common Toxicity Criteria Scale.

      The primary objective of Trial B is to evaluate the safety and biologic feasibility of the
      MTD of PDGF-B/Ad5 reported in Trial A in a standard 24-week trial for treatment of a venous
      leg ulcer. For this study, 15 consecutive patients will be treated using the MTD. All
      patients will receive a single intra-ulcer injection of PDGF-B/Ad5 and a limb compression
      bandage to be changed weekly.Study participants will be followed for 24 weeks, which is the
      length of most FDA-approved venous leg ulcer trials.
    

Intervention name(s): PDGF-B/Ad5
Intervention type(s): Drug
Intervention description(s): This is a dose finding study to evaluate the safety of a single injection of PDGF dna in an adenoviral vector.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Venous leg ulcer; Wound healing; Somatic gene therapy; PDGF-B