Effects of Subcutaneous Hyaluronidase Administration on Psoriatic Plaques
Condition: Psoriasis
MeSH terms: Psoriasis
Intervention: Hylenex; Normal Saline
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Psoriasis; Dendritic cells; Hyaluronidase; Hylenex

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of plaque psoriasis for at least 6 months, with at least 2 psoriatic plaques
             on different parts of the body that are both between 2-cm and 5-cm in diameter at the
             time of screening

          -  Age 18-65 years

          -  Male subjects who agree to use barrier methods for contraception throughout the course
             of the trial if their female partners are of child-bearing potential, or female
             subjects not of child-bearing potential

          -  Subject agrees to comply with study requirements

          -  Subject is fluent in English and is able to provide written informed consent

        Exclusion Criteria:

          -  Subjects with severe medical condition(s) that in the view of the investigator
             prohibits participation in the study

          -  Subject has Netherton's syndrome or other genodermatoses that result in a defective
             epidermal barrier

          -  Subjects who have applied topical medications (prescription or over-the-counter) for
             the treatment of psoriasis to their body within 7 days of the baseline visit

          -  Subjects who have taken cyclosporine, methotrexate, immuran, oral retinoids,
             chemotherapeutic agents, anti-inflammatory biologics (e.g., alefacept, etanercept,
             etc.), or oral calcineurin inhibitors within 28 days of the baseline visit

          -  Subjects who are unable to hold their current psoriasis medications for the period of
             time indicated (at least 7 days for topical medications, at least 28 days for oral or
             injectable medications) without significant worsening of their psoriasis

          -  Immunocompromised subjects (e.g., lymphoma, HIV/AIDS, Wiskott-Aldrich Syndrome), or
             subjects with a history of malignant disease (excluding non-melanoma skin cancer) as
             determined by the participant's medical history.

          -  Subjects receiving phototherapy (e.g., ultraviolet light B [UVB], psoralen plus
             ultraviolet light A [PUVA]) within 28 days of the baseline visit

          -  Subjects with a history of psychiatric disease or history of alcohol or drug abuse
             that would interfere with the ability to comply with the study protocol

          -  Subjects with significant concurrent medical condition(s) at screening that in the
             view of the investigator prohibits participation in the study (e.g., severe concurrent
             allergic disease, condition associated with malignancy, and condition associated with
             immunosuppression)

          -  Subjects who have used any systemic antibiotics within 28 days of the baseline visit

          -  Subjects with an active bacterial, viral or fungal skin infection (excluding nail
             fungus)

          -  Subjects currently receiving lithium or have received lithium within the last 4 weeks.

          -  Ongoing participation in an investigational drug trial

          -  Subjects with diabetes requiring medication

          -  Presence of psoriasis with exfoliative erythroderma or presence of guttate psoriasis,
             primary palmoplantar psoriasis, or pustular psoriasis

          -  Hypersensitivity to hyaluronidase or any other ingredient in the formulation of
             hyaluronidase, as well as subjects with an allergy or hypersensitivity to lidocaine

          -  Subjects taking furosemide, benzodiazepines, phenytoin, salicylates, cortisone,
             antihistamines or estrogens