Clinical trial NCT01987609
Conditions: Psoriasis
Keywords: Psoriasis Dendritic cells Hyaluronidase Hylenex
Sponsor: Tissa Hata, MD
Start date: 2015-07-01; Completion date: 2018-02-01
Enrollment: 7 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Arms: arm 1: Psoriatic plaques in this arm will be injected with Hylenex every week for 4 weeks. arm 2: Psoriatic plaques in this arm will be subcutaneously injected with sterile normal saline every week for four weeks
Interventions: intervention 1: Hylenex intervention 2: Normal Saline
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_SAP_000.pdf: 
 
 
UCSD Human Research Protections Program 
New Biomedical Application 
RESEARCH PLAN 
Version Date: 03/20/2017 
1. 
PROJECT TITLE 
Evaluation of the effect of subcutaneous hyaluronidase administration on psoriatic plaques 
2. 
PRINCIPAL INVESTIGATOR 
Tissa Hata, M.D., Clinical Professor and Director of Clinical Trials, UCSD 
3. 
FACILITIES 
UCSD Dermatology Outpatient Clinic (University Center Lane, La Jolla) 
4. 
ESTIMATED DURATION OF THE STUDY 
3 years 
5. 
LAY LANGUAGE SUMMARY OR SYNOPSIS (no more than one paragraph) 
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 psoriaisis. Research 
recently conducted in Dr. Gallo’s lab 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, we plan to inject recombinant human hyaluronidase (Hylenex®) subcutaneously below a psoriatic 
plaque in human psoriasis patients every week for a total of 4 weeks.  Each week we will measure the clinical 
appearance of the plaque.  At visit 5we will also take skin biopsies of the treated plaque to visualize the 
histology of the plaque and look for changes in expression of different inflammatory markers. 
6. 
SPECIFIC AIMS 
 To determine whether administration of subcutaneous hyaluronidase (Hylenex®) into a psoriasis plaque is 
able to improve its clinical appearance 
 To determine whether administration of subcutaneous hyaluronidase (Hylenex®) into a psoriasis plaque is 
able to change its histologic appearance 
 
If there appears to be either a clinical or histologic change in the psoriatic plaque after subcutaneous 
hyaluronidase (Hylenex®) administration, we will also attempt the following aim: 
 
 
To determine whether administration of subcutaneous hyaluronidase (Hylenex®) into a psoriasis plaque 
down-regulates the expression of inflammatory markers interferon α (INFα), tumor necrosis factor α 
(TNFα), Toll-like receptor (TLR) 7, TLR 8, or TLR 9  
7. 
BACKGROUND AND SIGNIFICANCE 
Psoriasis is a chronic inflammatory skin condition affecting approximately 2% of the population1.  Affected 
patients experience raised, well-demarcated, erythematous plaques with an overlying silvery scale on various 
parts of their skin.  These lesions are associated with significant morbidity. Patients are embarrassed by the 
appearance of their skin; the lesions can be extremely itchy, causing distraction and difficulty sleeping; and 
most medications have significant side effects. In addition, patients with psoriasis, like those with other major 
medical disorders, have reduced levels of employment and income as well as a decreased quality of life2,3.  
 
The pathogenesis of psoriasis is thought to be initiated by triggers such as physical trauma or bacterial products 
that start a cascade of events, including the formation of self-DNA/LL-37 complexes.  These complexes are 
recognized by Toll-like receptors on dendritic cells, activating the dendritic cells and causing them to secrete 
IFN-α. Activated dendritic cells then migrate into draining lymph nodes and induce the differentiation of naive 
T cells into effector cells such as type 17 helper T cells (Th17) or type 17 cytotoxic T cells (Tc17) and type 1 
helper T cells (Th1) or type 1 cytotoxic T cells (Tc1). Effector cells continue to recirculate, and immune cells 
expressing the chemokine receptors CCR6, CCR4, and CXCR3 emigrate into skin tissue along chemokine 


 
 
Biomedical IRB Application  
Page 2 
gradients. 
 
Current therapeutic options for psoriasis target different points in the psoriatic cascade described above, 
including cytokines secretion and T cell activation and differentiation.  Another therapeutic option, psoralen 
and ultraviolet A (PUVA), has been shown to reduce the number of dendritic cells in patients with psoriasis, 
providing key support for the role of these cells in the psoriatic cascade.  Furthermore, A functional and 
potentially therapeutic role of dendritic cells as potential drug targets has also been shown in models of 
psoriasis50.  In this study we hope to confirm the role of dendritic cells as a therapeutic target in psoriasis by 
injecting psoriatic plaques with an enzyme shown to decrease dendritic cell abundance in the animal model 
described below. 
 
Hyaluronan is a major component of the dermal and epidermal extracellular matrix.  An extraordinarily wide 
variety of biological functions have been attributed to HA including roles as a space-filling molecule 
maintaining hydration, lubrication of joints and actions in angiogenesis (19), and immune regulation (21, 22).  
Although the nascent size of hyaluronan is typically very large, large molecular weight hyaluronan undergoes 
breakdown after wounding into small fragments. These hyaluronan fragments can then interact with endothelial 
cells, macrophages and dendritic cells.  Dr. Gallo’s lab recently set out to investigate the role of hyaluronan 
breakdown in vivo using a transgenic mouse model overexpressing hyaluronidase, the enzyme responsible for 
breaking larger molecular weight hyaluronan into fragments.  Results from these studies showed that 
hyaluronidase over-expressing mice had a significantly lower number of dendritic cells in the dermal 
compartment of the skin compared to wild type mice.  The mice were otherwise morphologically normal 
compared to wild type mice and had no significant laboratory abnormalities during a hematologic survey that 
included a complete blood count, blood chemistry, coagulation and bleeding time except for a slight but 
significant increase in LDL.  Since dendritic cells also play a role in mounting an inflammatory response to 
contact allergens, the ability of the hyaluronidase over-expressing mice were also tested to determine whether 
or not they were able to mount an allergic response.  The transgenic mice were sensitized with the hapten 
eFluor670, which is known to cause a contact hypersensitivity reaction in wild type mice.  Cutaneous 
inflammation was neither observed visually nor detected biochemically in the transgenic mice after application 
of this agent, suggesting that these mice were unable to mount an immune response to the agent because they 
lacked a sufficient number of dermal dendritic cells to mount an allergic response to this agent.  Taken together, 
these results in these mice suggest that hyaluronidase overexpression, which causes breakdown of high 
molecular weight hyaluronan into small fragments, lack dendritic cells in their dermis that can prevent antigen 
presentation and reduce the resulting inflammatory cascade usually caused by exogenous stimuli. 
 
In this study, we propose a plan that would allow us to test our hypothesize that hyaluronidase may have a role 
in treating psoriasis by reducing the number of dendritic cells in the dermis.  Since dendritic cells play a key 
role in the inflammatory cascade of psoriasis, reducing their expression in the dermis could prevent the 
propagation of this inflammatory cascade.   
 
Hylenex® is a recombinant form of human hyaluronidase that is FDA- approved for subcutaneous 
administration as an adjuvant for subcutaneous fluid administration for achieving hydration, to increase the 
dispersion and absorption of other injected drugs, and in subcutaneous urography for improving resorption of 
radiopaque agents.  In this study we will inject Hylenex® subcutaneously beneath a psoriatic plaque every 
week for 4 weeks.  Over the course of those 4 weeks we will observe the plaque for clinical changes.  After the 
last administration of the drug, we will also do a skin biopsy of the treated plaque to determine whether any 
histologic changes have occurred.  If there do appear to be histologic signs of psoriasis improvement, we will 
run RT-PCR of a second biopsy taken at the same time as the first biopsy to determine the expression levels of 
inflammatory cytokines such as IFN-α and receptors of inflammatory signals such as Toll-like receptors (TLR) 
7-9 are different in these psoriatic plaques. 


 
 
Biomedical IRB Application  
Page 3 
 
8. 
PROGRESS REPORT 
None. 
9. 
RESEARCH DESIGN AND METHODS 
Participation in this study will consist of a total of 5 visits (plus 2 optional visits for a total of 7 visits) to the 
UCSD Dermatology Clinic over approximately a three-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 patient will also be blinded as to which plaque is being injected with which 
treatment. 
 
During the first 4 visits, we will be injecting the plaques with 1-mL of Hylenex® or 1-mL of sterile 
(pharmaceutical grade) normal saline (NS).  1-mL of Hyelenx® 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 Hyelenx® injection persist 24 hours after injection, but 
this barrier is completely restored after 48 hours.  We expect cutaneous dendritic cells residing in the epidermis 
to migrate away from the epidermis through either lymphatic or vascular channels after Hylenex® is injected.  
This process should take only a few hours.  Since cutaneous dendritic cells are thought to turnover only every 
1-2 weeks, we would not expect new dendritic cells to 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, we hope that during the month-long period while 
patients are receiving Hylenex® injections, the inflammatory cascade triggering their psoriasis will be turned 
off, allowing their affected plaques to heal without further propagation of psoriasis.  We therefore hope to see 
differences in the Hylenex®-treated versus the NS-treated plaques both morphologically and histologically 
when we complete our final set of biopsies on the Visit 5. 
 
 
The specific procedures planned for each visit are described below: 
 
Screening/Baseline Visit (Visit 1/Day -28 to 1): After signing informed consent, participants will first be 
screened to ensure that they are eligible for the study.  This includes undergoing any necessary wash-out period 
in the case that the subject has treated their psoriasis with any topical agents (topical steroids, vitamin D, or 
calcineurin inhibitors) within 7 days of the screening/baseline visit, or any oral or injectable treatments 
(cyclosporine, methotrexate, immuran, oral retinoids, chemotherapeutic agents, anti-inflammatory biologics 
such as alefacept, etanercept, or oral calcineurin inhibitors) within 28 days of the screening/baseline visit.  If 
patients have taken one of these medications within the specified time and are still interested in participating in 
the study, they must hold that medication for a total of 7 days for topical agents and 28 days for oral/injectable 
agents and return for a baseline visit.  For subjects who are eligible for the study, we will then take a brief 


 
 
Biomedical IRB Application  
Page 4 
medical history and do a physical exam.  Next we will choose two of their psoriasis plaques to monitor 
throughout the study.  Both plaques must be between 2-cm and 5-cm in diameter, and must be in different 
locations on the body (either on different extremities or one on an extremity and the other on the trunk).  One of 
these plaques will be treated with Hylenex® over the course of the trial, while the other will be treated with NS 
to use as a control plaque.  First we will take pictures of the two plaques using a digital camera in order to 
visually compare the plaques and to use as a reference for determining the location of the plaque in future visits 
should the plaque(s) resolve over the course of the trial.  The photographs will not contain any identifying 
information.  They will be uploaded onto a password-protected computer and saved under the patient’s unique 
study identification number, which will not be traceable to any identifying information about the patient on the 
computer.  A blinded investigator will grade the severity of the plaques using known psoriatic grading scales 
such as the Physician’s Global Assessment (PGA) and the Psoriasis Area and Severity Index (PASI) and will 
also take measurements of the plaque sizes.  The unblinded investigator will then do one (1) 4-millimeter punch 
biopsies of the two plaques.  These biopsies will be fixed in formalin for histologic examination (to be read by 
Dr. Hinds), and will be frozen for later use for RT-PCR to determine expression levels of inflammatory 
cytokines and receptors including TNFα, IFNα, and TLR 7, 8 and 9.  There will not be any genetic testing done 
on this tissue, nor will it be stored for later use in other research projects.  We will then inject a single dose (1 
mL, or 150 units) of Hylenex® subcutaneously under the skin of the plaque designated the treatment plaque.  
We will next inject the control plaque with 1 mL NS subcutaneously. We will monitor the patient for thirty (30) 
minutes after the injection to ensure the patient does not have a reaction to the injections prior to them leaving 
the clinic.  The total length of this visit will be approximately one hour and 15 minutes. 
 
 Visit 2 (Day 8 +/- 1): Participants will return to the clinic, where we will first record any adverse events since 
the last visit.  We will take digital photographs of the two psoriasis plaques of interest in this study to document 
changes in the plaque since the last visit.  The photographs will not contain any identifying information.  Next 
the blinded investigator will grade the severity of the psoriasis plaques of interest using the PGA and PASI 
scores, as well as by taking measurements of the plaque sizes.  The unblinded investigator will then administer 
a 1 mL (equivalent to 150 units) dose of Hylenex® under the skin of the same plaque injected at Visit 1.  We 
will next administer a subcutaneous injection of 1 mL NS to the control plaque.  We will monitor the patient for 
thirty (30) minutes after the injections to ensure the patient does not have a reaction to the injection prior to 
them leaving the clinic.  The total length of this visit will be approximately 45 minutes. 
 
Visit 3 (Day 15 +/- 1): The activities of Visit 3 will be identical to those of Visit 2 
 
Visit 4 (Day 22 +/- 1): The activities of Visit 4 will be identical to those of Visit 2 
 
Visit 5 (Day 29 +/- 1):  We will first record any adverse events.  We will take digital photographs of the two 
psoriasis plaques of interest in this study to document changes in the plaques since the last visit.  The 
photographs will not contain any identifying information.  The blinded investigator will then grade the severity 
of the psoriasis plaques of interest, including size measurements.  Finally, the unblinded investigator will 
perform to one (1) 4-millimeter punch biopsies of the plaque we injected with Hylenex® during previous visits, 
and one (1) 4-millimeter punch biopsies of the plaque we previously injected with NS.  The  biopsy from both 
the treatment and control psoriatic plaques will be fixed in formalin for histologic examination (to be ready by 
Dr. Robert Lee or Dr. Casey Carlos), and will be stored at -80° Celsius for later use for RT-PCR to determine 
expression levels inflammatory cytokines and receptors such as TNFα, IFNα, and TLR 7, 8 and 9.  The total 
length of this visit will be approximately 30 minutes. 
 
Phone 1 (Day 59 +/- 7):  
Subjects will be called approximately one month after Visit 5.  Patients can opt for an optional in-clinic visit 


 
 
Biomedical IRB Application  
Page 5 
instead of a phone call if so desired. During this phone call, subjects will be asked about any adverse events 
(including serious adverse events) since their last follow-up visit, as well as how their psoriasis is currently 
doing. If patients opt for an in-clinic visit, digital photographs of the two psoriasis plaques of interest will be 
taken to document changes in the plaques since the last visit. The photographs will not contain any identifying 
information.  
 
Phone 2 (Day 109 +/- 7):  
Subjects will be called approximately 2 months after Visit 5. Patients can opt for an optional in-clinic visit 
instead of a phone call if so desired. During this phone call, subjects will be asked about any adverse events 
(including serious adverse events) since their last follow-up visit, as well as how their psoriasis is currently 
doing. If patients opt for an in-clinic visit, digital photographs of the two psoriasis plaques of interest will be 
taken to document changes in the plaques since the last visit. The photographs will not contain any identifying 
information. Although this phone contact or in-clinic visit will be the last scheduled contact for subjects with 
respect to this study, any subject with an ongoing adverse event (including serious adverse event) at the time of 
this phone contact/clinic visit will continue to be followed by study personnel until resolution of the event. 
 
 
Statistics 
Sample size calculation: Since this study is a proof-of-concept pilot study, there is no sample size calculation 
for this study.   
Comparison of psoriatic plaques:  
The treated plaque for each individual will be compared at each visit to the previous visit in terms of PGA, 
PASI and area using a paired t-test.   
Each participant’s baseline biopsy for histology will be compared to the histology of the treated plaque by our 
dermatopathologist to determine whether there appears to be any histologic changes in the plaque treated with 
Hylenex® compared to the untreated plaque. These histologic changes will include the number of dendritic 
cells in particular slices of the biopsy, as well as histologic markers of psoriasis severity. 
Each participant’s baseline biopsy for expression levels of inflammatory cytokines and receptors including 
TNFα, IFNα, and TLR 7, 8 and 9 will be compared to the expression levels of these cytokines and receptors in 
the treated psoriatic plaque using a paired t-test. 
 
10. 
HUMAN SUBJECTS 
Ten patients with a clinical diagnosis of psoriasis on physical exam will be recruited for this study.  All subjects 
will be between the ages of 18 and 65.  Enrollment will not take race or gender into consideration.  Women of 
child-bearing potential (pre-menopausal females who have not been surgically sterilized), children (under age 18), 
and unhealthy subjects with significant co-morbid conditions as determined by the PI will be excluded. 
 
This study is planned as a single center at the University of California, San Diego. 
 
SUBJECT ELIGIBILITY 
 
Inclusion Criteria:  
Those who meet all of the following criteria are eligible for enrollment into the study:      
1.         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 
2.         Age 18-65 years 
3. 
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 
4. 
Subject agrees to comply with study requirements 


 
 
Biomedical IRB Application  
Page 6 
5.         Subject is fluent in English and is able to provide written informed consent 
 
Exclusion Criteria: 
1. Subjects with severe medical condition(s) that in the view of the investigator prohibits participation in the study 
2. Subject has Netherton’s syndrome or other genodermatoses that result in a defective epidermal barrier 
3.  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 
4.  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 
5.  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 
6. 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. 
7.  Subjects receiving phototherapy (e.g., ultraviolet light B [UVB], psoralen plus ultraviolet light A [PUVA])  
     within 28 days of the baseline visit 
8. 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 
9. 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) 
10.  Subjects who have used any systemic antibiotics within 28 days of the baseline visit 
11.  Subjects with an active bacterial, viral or fungal skin infection (excluding nail fungus) 
12.  Subjects currently receiving lithium or have received lithium within the last 4 weeks. 
13.  Ongoing participation in an investigational drug trial 
14.  Subjects with diabetes requiring medication 
15.  Presence of psoriasis with exfoliative erythroderma or presence of guttate psoriasis, primary palmoplantar  
        psoriasis, or pustular psoriasis 
16.  Hypersensitivity to hyaluronidase or any other ingredient in the formulation of hyaluronidase, as well as  
       subjects with an allergy or hypersensitivity to lidocaine 
17.  Subjects taking furosemide, benzodiazepines, phenytoin, salicylates, cortisone, antihistamines or estrogens 
 
REMOVAL AND REPLACEMENT OF SUBJECTS 
Subjects have the right to withdraw fully or partially from the study at any time and for any reason without 
prejudice to his or her future medical care by the physician or at UCSD.  All data generated up to the time of 
discontinuation from the study will be analyzed and the reason for discontinuation will be recorded.  
11. 
RECRUITMENT 
Patients will be recruited from the practice of the investigators (once the study starts, investigators will ask 
psoriasis patients who they see in their clinic if they are interested in participating in a clinical trial), online 
advertisements placed on Craigslist, and fliers.  Recruitment will be performed by investigators and study 
coordinators.  All recruitment materials will receive approval from the IRB before utilization. Involvement will be 
completely voluntary (no coercion) and all risks will be clearly outlined and explained prior to enrollment. 
Involvement will not lead to promotion or any salary compensation. 
12. 
INFORMED CONSENT 
Informed consent is an ongoing process that includes the signing of an informed consent form. Subjects will be 
required to sign an informed consent form prior to being screened and before undergoing any study procedures or 


 
 
Biomedical IRB Application  
Page 7 
assessments, in accordance with ICH E6; 4.8, “Informed Consent of Trial Subjects.  The informed consent 
process will occur at the UCSD outpatient dermatology clinic in La Jolla. After first being told about the study 
and its risks and benefits, participants will be given a minimum of 3 days to fully consider their willingness to 
participate in the study before coming in to sign the consent form during their screening visit.  Before any other 
procedures at the screening visit, subjects will be provided with a copy of the informed consent form and printed 
materials that explain the purpose of the study, procedures, and assessments. Subjects will also be provided with 
the telephone numbers of the investigator and qualified personnel who can assist with their questions and 
concerns.  Members of the research team listed below will be involved in this consenting procedure.  Once the 
consent form has been signed and dated, the participant can proceed with the screening procedures. 
 
Please see attached consent form. 
 
Withdrawal of full consent for a study means that the subject does not wish to receive further investigational 
treatment and does not wish to or is unable to continue further study participation.  Any subject may withdraw full 
consent to participate in the study at any time during the study.  The investigator will discuss with the subject the 
most appropriate way to withdraw to ensure the subject’s health.  Patients may withdraw their consent at any 
point in the study without risk of compromising future care at UCSD. 
13. 
ALTERNATIVES TO STUDY PARTICIPATION 
The alternative to participating would be not to participate in the trial.  Patients not wanting to enroll in the 
study but still wanting to treat their psoriasis will need to see a dermatologist to discuss other therapeutic 
options, which include topical steroids, methotrexate and biologics. 
14. 
POTENTIAL RISKS 
Risks of Hylenex® 
Hylenex® has been FDA-approved as an adjuvant in subcutaneous fluid administration for achieving 
hydration, to increase the dispersion and absorption of other injected drugs, and in subcutaneous urography for 
improving resorption of radiopaque agents in the same dosages being used in this study.  Nonetheless, the use 
of Hylenex® still has risks.  These risks will be listed below: 
1. The most frequently reported adverse reactions to Hylenex® have been local injection site reactions 
such as erythema and pain in response to Hylenex® injections.  These reactions are self-limited and 
tend to resolve spontaneously over a period of a few days.   
2. Hypersensitivities or allergies to hyaluronidase or any other ingredient in the formulation have been 
reported in less than 0.1% of patients receiving Hylenex®.  Rare anaphylactic-like reactions after 
Hylenex® administration have occurred, but only after retrobulbar blocks or intravenous injections. 
Although neither of these routes of administration will be used in this study, an anaphylactic reaction is 
possible. 
3. Hylenex® recombinant contains albumin, which is a derivative of human blood that may carry a remote 
risk of transmitting infectious agents, e.g., viruses and theoretically, the Creutzfeldt-Jakob disease 
(CJD) agent. No cases of transmission of viral diseases, CJD, or variant CJD (vCJD) have ever been 
identified for licensed albumin or albumin contained in other licensed products. 
4. Hyaluronidase is antigenic; repeated injections of relatively large amounts of hyaluronidase preparations 
may result in the formation of neutralizing antibodies.  Since we are only administering 4 injections of 
Hylenex®, each containing the dose recommended by the manufacturer, we do not anticipate antibody 
production to be an issue. 
5. Hylenex® can enhance the spread of local infections when administered in an infected site.  Psoriatic 
plaques do not typically get infected, however we will avoid injecting the medication into a plaque that 
appears to be infected or is surrounded by skin with clinical signs of infection or excoriations 
representing recent trauma to the skin.   
6. Hylenex® is categorized as Pregnancy Class C by the FDA (Animal reproduction studies have shown 


 
 
Biomedical IRB Application  
Page 8 
an adverse effect on the fetus and there are no adequate and well-controlled studies in humans) 
 
For additional information on the risks of Hylenex®, please see the product insert included with this 
submission. 
 
Risks of Normal Saline 
Normal saline is a solution commonly used in biological research. It is a salt solution with an osmolarity that 
matches that of the human body (isotonic), therefore we do not expect there to be risks associated with 
subcutaneous administration of this medication. 
 
Risks associated with Hylenex®/NS injections 
Risks associated with injecting Hylenex®/NS include the following: 
1. Pain 
2. Tenderness at the injection site for a few days 
3. Worsening of psoriasis at the injection site 
4. Infection 
5. Redness and/or swelling at the site of the injection 
 
Risks of medication withdrawal 
Discontinuation of a person’s psoriasis medication prior to participating in this study may result in worsening 
of the patient’s psoriasis.  After the study, patients will be allowed to resume their standard psoriasis treatment 
regimens, however during the study they will not be permitted to use their regular medications or any other 
medications for psoriasis.  Subjects’ usual treatment regimens are still expected to be efficacious after 
participating in the study, however if the patient’s psoriasis is much worse than before the study, they may need 
to temporarily increase the strength or dose of their regular psoriasis medications.  Patients will be advised to 
see the dermatologist who prescribes their medications to help them in making any such medication 
adjustments.  Similarly, if Hylenex® use improves a patient’s psoriasis, discontinuation of this medication at 
the end of the study may cause worsening of their psoriasis.  We would recommend patients resume their 
regular psoriasis medications at the end of the study to prevent this rebound effect from happening.  We would 
expect the patient’s psoriasis to respond to their usual medication regimen just as it did before participating in 
the study. 
 
Risks of a skin biopsy 
The following are potential risks of a skin biopsy: 
 
1. 
Bleeding, infection, pain, and/or discomfort at the site of the biopsies.  
2. 
The biopsied areas will be tender for a few days following the procedures. 
3. 
The biopsy procedures will result in a small scar. 
4. 
The skin may become temporarily inflamed (swollen) as a result of these procedures. 
5. 
The subject may experience an allergic reaction (itchy rash on the body or fainting) to the  
            numbing medication.  
6. 
The biopsy site may develop an increase or decrease in the pigmentation (color) of the skin.  
 
Risk of Loss of Confidentiality 
Samples will be labeled with the subject identification number prior to storage and only study investigators and 
study coordinators will have access to the patients’ identifying information. The patients name and sample/test 
results will be stored separately and securely, but the principal investigator and site study staff will know which 
samples belongs to which patients until one year following the end of this study. At that time, the link between 
the subject and their sample will be destroyed and it will not be possible to determine which samples belong to 


 
 
Biomedical IRB Application  
Page 9 
a particular patient. A patient may withdraw their sample from the study any time before the link between the 
patient and the sample is broken.  Study participants will not be identified by name on any study documents.  
The study-related records will be maintained by the investigator. All study-related records (patient charts and 
other study records) must be retained at least 3 years after data analysis is complete.  Patients will be reassured 
that PHI will not be re-used or disclosed for other purposes. 
15. RISK MANAGEMENT PROCEDURES AND ADEQUACY OF RESOURCES 
Risk management procedures related to Hylenex® were discussed above in Section 14.  These procedures 
include: 
 Avoidance of Hylenex® injections in patients with an active skin infection 
 Administering Hylenex® only in the dosages recommended by the manufacturer 
 Not administering Hylenex® intravenously 
 Female subjects of child-bearing potential will not be enrolled in the study unless surgically sterilized, 
and male subjects whose partners are of child-bearing potential must agree to use barrier contraceptive 
methods during the course of the study. 
 
Further risk management strategies related to Hylenex® injections include the following: 
All adverse events will be seriously considered to determine whether or not they are related to the study 
procedures, including the administration of Hylenex®.  Any participants having an adverse event related to the 
study procedures will be considered for withdrawal from the study.  The PI will be responsible for determining 
whether it is in the subject’s best medical interest to be removed from the study. 
 
Risk management strategies related to drug injections: 
In order to minimize the potential for an infection after drug injections, we will use a sterile need for all 
injections.  Needles will not be re-used on the same or different people.  We will also clean each plaque we are 
going to inject with an alcohol swab prior to doing the injection. 
 
Risk management strategies related to skin biopsies: 
To minimize potential risks, skin sites for biopsy will be cleaned. Patients will be excluded from study with 
known tape or anesthetic allergy. The procedure will be done under aseptic conditions, and bleeding controlled 
by standard dermatologic techniques of pressure of electrocautery wound care instructions will be provided to 
all patients. It is extremely unlikely that an adverse reaction will occur as these procedures are routinely 
performed at our institution with rare (less than 1/10,000) reports of adverse effects. In the event of adverse 
outcome, all patients are provided with wound care instructions that contain emergency contact information for 
the dermatology service. If the subject is injured as a result of participation in this research, treatment will be 
available. 
 
Risk management strategies to avoid loss of confidentiality: 
To protect patient confidentiality, all samples will be encoded and anonymous.  The link between subjects and 
their study identifier will be stored under lock and key, only accessible to the study coordinator and the PI.  
Strict adherence to current HIPPA guidelines will also minimize the risk of loss of confidentiality. 
 
 
Site resources: 
The outpatient dermatology clinic at UCSD is fully staffed with between 5 to 7 physicians and up to 6 ancillary 
medical personnel (registered nurses and medical assistants) at any given time during regular business hours.  
In case of an emergency including a type 1 hypersensitivity reaction such as anaphylaxis, the clinic has 
automated machines for taking vitals; an automatic external defibrillator; and an emergency box containing 
needles and syringes, an epinephrine pen, a non-rebreather mask with tubing that can be connected to one of 


 
 
Biomedical IRB Application  
Page 10 
several oxygen outlets in the clinic, and a first-aid kit.  All of these emergency supplies are checked daily to 
ensure that they are well-stocked and functional.  Furthermore, our clinic is located within 3 miles of the 
UCSD-affiliated Thornton Hospital.  Emergency personnel will be contacted to transport subjects to this 
location should subjects require an escalated level of care. 
 
The subject may call the Human Research Protections Program at (858) 246-HRPP (4777) to inquire about 
their rights as a research subject or to report research related problems. 
16. PRIVACY AND CONFIDENTIALITY CONSIDERATIONS INCLUDING DATA ACCESS AND MANAGEMENT 
Personal information will be kept confidential and will be maintained at the UCSD Dermatology Outpatient 
Clinic in La Jolla. All research records will be labeled with a code number so that they are de-identified. The 
list that matches the patient’s name with their code number will be kept in a locked file at the UCSD 
Dermatology Clinic on the 3rd floor of University Pacific Center in La Jolla. The research records will be kept 
only as paper records in a secure location, or as files behind the secure computer firewall. Digital photographs 
will be identified by participants’ code number, and will not contain any identifying information about the 
participant.  Photographs will not be used in any publications or for any future uses.  Any presentations or 
publications from this information will not identify any personal information.  Identifying information will only 
be available to the study PI and study coordinator conducting patient visits.  De-identified information will be 
available to all other persons involved with the research study.   
17. POTENTIAL BENEFITS 
Animal studies conducted in our lab on mice suggest that subcutaneous hyaluronidase may improve psoriasis 
plaques.  If this is true, patients may experience improvement or even clearing in the psoriasis plaque that is 
treated.  This information may be beneficial to the population of psoriasis patients in general, and may also 
promote further research leading to more knowledge regarding the effects of hyaluronic acid on psoriasis. 
18. RISK/BENEFIT RATIO 
Skin biopsies are relatively safe and well-tolerated.  Hylenex® is a relatively safe drug that is generally well-
tolerated with few side effects.  Animal studies have suggested that administration of this drug may improve 
psoriasis.  If so, not only will enrolled subjects benefit from improvement of their psoriasis, but also the 
population of patients with psoriasis could one day benefit from the findings in this study.  It is also possible 
that a patient’s psoriasis may not change with our dosing and frequency of Hylenex® administration.  
Alternatively, patients’ psoriasis may even worsen with Hylenex®, however they may withdraw from the study 
if they feel that their psoriasis is worsening and they do not wish to continue in the study.  Given the relatively 
low risk of the medication and the potential for patients to have an improvement in their psoriasis, it seems that 
the benefits of the study would outweigh the risks. 
19. EXPENSE TO PARTICIPANT 
None.  Hylenex will be provided free of charge to participants. 
20. COMPENSATION FOR PARTICIPATION 
Participants will be compensated $50 per visit for completing Visit 1, $20 each for completing Visits 2, 3 and 4, 
and $50 for completing Visit 5.  Payments will be issued in the form of a payment authorization through 
UCSD.  A single payment authorization for $160 will be issued to each participant upon the participant’s 
completion of the study.  If a person withdraws from the study (voluntarily or otherwise) before completing all 
of the study procedures, they will be issued a payment authorization for the total sum of money owed to them 
based which visits they completed. 
 
21. PRIVILEGES/CERTIFICATIONS/LICENSES AND RESEARCH TEAM RESPONSIBILITIES 
Dr. Tissa Hata will be primarily responsible for overseeing the clinical portion of this study.  Dr. Hata holds a 
California Medical License and she is a Clinical Professor in the Department of Dermatology and Director of 
Clinical Trials in the Department of Dermatology.   
 


 
 
Biomedical IRB Application  
Page 11 
Yun Tong, MD, is a Clinical Research Fellow who will be involved in study coordination, enrollment 
interviews and informed consent discussions. He will serve as the unblinded coordinator and therefore will also 
be responsible for administration of the study drug.  He will also serve as the study pharmacist and therefore 
will also be responsible for the storage and proper handling of study drug.  Dr. Tong is licensed to practice 
medicine in the State of California. He currently serves as the pharmacist for several industry-sponsored 
clinical trials in the Department of Dermatology. 
 
Dr. Brian Hinds is an Assistant Clinical Professor in the Department of Dermatology.  He is a board-certified 
Dermatologist and fellowship-trained/board-certified in Dermatopathology.  Dr. Lee holds a California Medical 
License. He will be responsible for analyzing the skin biopsies taken in this study. 
 
22. BIBLIOGRAPHY 
1. Christophers E. Psoriasis -- epidemiology and clinical spectrum. Clin Exp Dermatol 2001;26:314-320 
2. Horn EJ, Fox KM, Patel V, Chiou CF, Dann F, Lebwohl M. Association of patient-reported psoriasis 
severity with income and employment. J Am Acad Dermatol 2007;57:963-971 
3. Gelfand JM, Feldman SR, Stern RS, Thomas J, Rolstad T, Margolis DJ. Determinants of quality of life 
in patients with psoriasis: a study from the US population. J Am Acad Dermatol 2004;51:704-708 
4. Nestle FO, Conrad C, Tun-Kyi A, et al. Plasmacytoid predendritic cells initiate psoriasis through 
interferon-alpha production. J Exp Med 2005;202:135-143 
23. FUNDING SUPPORT FOR THIS STUDY 
Funding will be internal through the UCSD Department of Dermatology and through a Fellowship Grant from 
the National Psoriasis Foundation.   
24. BIOLOGICAL MATERIALS TRANSFER AGREEMENT 
N/A 
25. INVESTIGATIONAL DRUG FACT SHEET AND IND/IDE HOLDER 
IND# 119899 
26. IMPACT ON STAFF 
None. 
27. CONFLICT OF INTEREST 
None. 
28. SUPPLEMENTAL INSTRUCTIONS FOR CANCER-RELATED STUDIES 
N/A 
29. OTHER APPROVALS/REGULATED MATERIALS 
None. 
30. PROCEDURES FOR SURROGATE CONSENT AND/OR DECISIONAL CAPACITY ASSESSMENT 
N/A (persons without decisional capacity or those needing a surrogate consenter will not be enrolled)