Effects of Subcutaneous Hyaluronidase Administration on Psoriatic Plaques
Condition: Psoriasis
MeSH terms: Psoriasis
Study type: Interventional
Phase: Phase 2

Summary: 
      Dendritic cells are a key component of the inflammatory response seen in psoriasis. Several
      current psoriasis therapies have been shown to reduce the number of dendritic cells in
      patients with psoriasis, leading researchers to believe that therapies specifically targeting
      dendritic cells may lead to improvement in psoriasis. Research recently conducted in Dr.
      Gallo's lab at the University of California San Diego has shown that transgenic mice
      overexpressing the enzyme hyaluronidase have a significant decrease in the number of
      dendritic cells in the dermal component of their skin compared to wild type mice. If
      hyaluronidase overexpression in humans also decreases the number of dendritic cells in the
      dermis, then hyaluronidase therapy may improve the clinical presentation of psoriasis. In
      order to test this hypothesis, recombinant human hyaluronidase (Hylenex®) will be injected
      subcutaneously below a psoriatic plaque in human psoriasis patients every week for a total of
      4 weeks. Each week the clinical appearance of the plaque will be documented. At the final
      visit skin biopsies of the treated plaque will be taken to visualize the histology of the
      plaque and look for changes in expression of different inflammatory markers.
    

Detailed description: 
      Participation in this study will consist of a total of 5 visits to the UCSD Dermatology
      Clinic over approximately a one-month period. At the first visit, two psoriatic plaques
      between 2-cm and 5-cm in diameter to be studied in this trial will be agreed upon by the
      patient as well as the blinded and unblinded investigators. Preference will be given to
      plaques on the elbows since the elbow is a common place of psoriatic plaques, and since
      scarring on the elbows is usually more acceptable than scarring on other parts of the skin
      since the skin on the elbows is naturally hyperpigmented in most people. For the remainder of
      the study, all grading and measurements of the psoriatic plaques will be completed by a
      blinded investigator who is unaware of which plaque is receiving which treatment. An
      unblinded investigator will complete all other portions of the study visit, including digital
      photography, injecting the plaques, and completing the biopsies. The subject will also be
      blinded as to which plaque is being injected with which treatment.

      During the first 4 visits, plaques will be injected with 1-mL of Hylenex® or 1-mL of sterile
      (pharmaceutical grade) normal saline (NS). 1-mL of Hylenex® contains 150 Units of recombinant
      hyaluronidase. This is the standard dose of the drug that has been approved by the FDA, and
      therefore this dose is considered to be safe for use in adults. If injected subcutaneously
      into the center of a psoriatic plaque that is between 2 and 5 centimeters in diameter, this
      1-mL dose should be able to diffuse throughout the entire area beneath the plaque. The exact
      pharmacokinetics of Hylenex® are difficult to study due to its rapid inactivation after
      intravenous injection. According to the Hylenex® package insert, though, disruptions to the
      dermal barrier that occur in response to subcutaneous Hylenex® injection persist 24 hours
      after injection, but this barrier is completely restored after 48 hours. Cutaneous dendritic
      cells residing in the epidermis are thought to migrate away from the epidermis through either
      lymphatic or vascular channels after Hylenex® is injected. This process should take a few
      hours. Since cutaneous dendritic cells are thought to turnover only every several weeks, new
      dendritic cells should not populate the epidermis before patients receive the next injection
      of Hylenex®. Since dendritic cell activation initiates the inflammatory cascade thought to
      result in psoriasis, preventing dendritic cells from being harbored in the epidermis should
      essentially prevent the inflammatory cascade that results in psoriasis. Therefore, during the
      month-long period while patients are receiving Hylenex® injections, the inflammatory cascade
      triggering their psoriasis will potentially be turned off, allowing affected plaques to heal
      without propagation of further psoriasis. If this is true, there should be differences in the
      Hylenex®-treated versus the NS-treated plaques both morphologically and histologically upon
      completion of the final set of biopsies on the Visit 5.
    

Intervention name(s): Hylenex; Normal Saline
Intervention type(s): Drug; Drug
Other intervention name(s): Hylenex (R) recombinant; hyaluronidase human injection; Normal Saline, 0.9%
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Psoriasis; Dendritic cells; Hyaluronidase; Hylenex