Effects of Subcutaneous Hyaluronidase Administration on Psoriatic Plaques

Psoriasis Clinical Trial

Official title: Evaluation of the Effect of Subcutaneous Hyaluronidase Administration on Psoriatic Plaques

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Psoriasis

• NCT number: NCT01987609
• Study type: Interventional
• Source: University of California, San Diego
• Status: Completed
• Phase: Phase 2
• Start date: July 2015
• Completion date: February 2018