PsoriasisPhase 2NCT01987609
Effects of Subcutaneous Hyaluronidase Administration on Psoriatic Plaques
A Phase 2 study testing Hylenex and Normal Saline in people with Psoriasis, run by Tissa Hata, MD at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Psoriasis
- What is being tested?
- Hylenex and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2015to Feb 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSD Division of Dermatology
San Diego, California, 92122
About this study
Official title: Evaluation of the Effect of Subcutaneous Hyaluronidase Administration on Psoriatic Plaques
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.
Read the 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.
- Conditions
- Psoriasis
- Being tested
- Hylenex, Normal Saline
- Keywords
- Psoriasis, Dendritic cells, Hyaluronidase, Hylenex
- Medical subject headings
- Psoriasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HylenexDrug
Also called Hylenex (R) recombinant, hyaluronidase human injection
Normal SalineDrug
Also called Normal Saline, 0.9%
| Study group | Role | What they receive |
|---|---|---|
| Hylenex | Experimental | Psoriatic plaques in this arm will be injected with Hylenex every week for 4 weeks. Receives: Drug: Hylenex |
| Normal Saline | Placebo comparator | Psoriatic plaques in this arm will be subcutaneously injected with sterile normal saline every week for four weeks Receives: Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Psoriasis Area Severity Index
The Psoriasis Area Severity Index (PASI) of the psoriatic plaques of interest will be measured and compared to baseline values. The PASI is the most widely used tool for the measurement of severity of psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease).
Measured: 4 weeks
Secondary outcomes (13)
Plaque Area
A ruler/measuring tape will be used to measure the area of the subject's psoriatic plaques of interest.
Measured: 4 weeks
Plaque Area
A ruler/measuring tape will be used to measure the area of the subject's psoriatic plaques of interest.
Measured: 2 weeks
Plaque Area
A ruler/measuring tape will be used to measure the area of the subject's psoriatic plaques of interest.
Measured: 3 weeks
Plaque Area
A ruler/measuring tape will be used to measure the area of the subject's psoriatic plaques of interest.
Measured: 1 weeks
Physician Global Assessment (PGA)
The Physician Global Assessment (PGA) of the psoriatic plaques of interest will be measured and compared to baseline values on a 0-5 scale where 0 is no evidence of erythema, induration, or scaling, and 5 is severe evidence of these symptoms.
Measured: 3 weeks
Physician Global Assessment (PGA)
The Physician Global Assessment (PGA) of the psoriatic plaques of interest will be measured and compared to baseline values on a 0-5 scale where 0 is no evidence of erythema, induration, or scaling, and 5 is severe evidence of these symptoms.
Measured: 2 weeks
Physician Global Assessment (PGA)
The Physician Global Assessment (PGA) of the psoriatic plaques of interest will be measured and compared to baseline values on a 0-5 scale where 0 is no evidence of erythema, induration, or scaling, and 5 is severe evidence of these symptoms.
Measured: 1 week
Change in Histologic Appearance of Psoriatic Plaques
The histologic appearance of a skin biopsy taken from each of the plaques of interest at the end of the study (4 weeks) will be compared to biopsies taken at baseline. The most important feature to be observed is the number of dendritic cells in the different biopsy specimens.
Measured: baseline and 4 weeks
Change in Tumor Necrosis Factor Alpha (TNFα) Expression
RT-PCR techniques will be used to determine expression levels of the inflammatory cytokine TNFα in all skin biopsies. The expression levels of this cytokine in skin biopsies at week 4 will be compared to the expression levels at baseline.
Measured: 4 weeks
Change in Interferon Alpha (IFNα) Expression
RT-PCR techniques will be used to determine expression levels of the inflammatory cytokine IFNα in all skin biopsies. The expression levels of this cytokine in skin biopsies at week 4 will be compared to the expression levels at baseline.
Measured: 4 weeks
Change in Toll-like Receptor 7 (TLR-7) Expression
RT-PCR techniques will be used to determine expression levels of the TLR-7 in all skin biopsies. The expression levels of this receptor in skin biopsies at week 4 will be compared to the expression levels at baseline.
Measured: 4 weeks
Change in Toll-like Receptor 8 (TLR-8) Expression
RT-PCR techniques will be used to determine expression levels of the TLR-8 in all skin biopsies. The expression levels of this receptor in skin biopsies at week 4 will be compared to the expression levels at baseline.
Measured: 4 weeks
Change in Toll-like Receptor 9 (TLR-9) Expression
RT-PCR techniques will be used to determine expression levels of the TLR-9 in all skin biopsies. The expression levels of this receptor in skin biopsies at week 4 will be compared to the expression levels at baseline.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2013 (estimated)
- Study startJul 2015
- Primary completionMar 2017
- Study completionFeb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PsoriasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tissa Hata, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Tissa Hata, MD, University of California, San Diego
- Investigators
- Tissa Hata, MD, Principal investigator, UCSD Division of Dermatology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01987609
- Sponsor's protocol ID
- UCSD 131026
- Status last verified
- Dec 2018
- First submitted
- 12 Nov 2013
- Last updated
- 4 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Effect of Subcutaneous Hyaluronidase Administration on Psoriatic Plaques
- ClinicalTrials.gov ID
- NCT01987609
- Acronym / sponsor ID
- UCSD 131026
- Conditions
- Psoriasis
- Keywords
- Psoriasis, Dendritic cells, Hyaluronidase, Hylenex
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Tissa Hata, MDUniversity, hospital or other
- Study start
- Jul 2015 (actual)
- Primary completion
- Mar 2017 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 19 Nov 2013 (estimated)
- Results
- Posted 4 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hylenex | Experimental | Drug: HylenexPsoriatic plaques in this arm will be injected with Hylenex every week for 4 weeks. |
| Normal Saline | Placebo comparator | Drug: Normal SalinePsoriatic plaques in this arm will be subcutaneously injected with sterile normal saline every week for four weeks |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HylenexAlso: Hylenex (R) recombinant, hyaluronidase human injection | Drug | Hylenex |
| Normal SalineAlso: Normal Saline, 0.9% | Drug | Normal Saline |
Primary outcome
Psoriasis Area Severity Index
Time frame: 4 weeks
The Psoriasis Area Severity Index (PASI) of the psoriatic plaques of interest will be measured and compared to baseline values. The PASI is the most widely used tool for the measurement of severity of psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease).
13 secondary outcomes
Plaque Area
Time frame: 4 weeks
Plaque Area
Time frame: 2 weeks
Plaque Area
Time frame: 3 weeks
Plaque Area
Time frame: 1 weeks
Physician Global Assessment (PGA)
Time frame: 3 weeks
Physician Global Assessment (PGA)
Time frame: 2 weeks
Physician Global Assessment (PGA)
Time frame: 1 week
Change in Histologic Appearance of Psoriatic Plaques
Time frame: baseline and 4 weeks
Change in Tumor Necrosis Factor Alpha (TNFα) Expression
Time frame: 4 weeks
Change in Interferon Alpha (IFNα) Expression
Time frame: 4 weeks
Change in Toll-like Receptor 7 (TLR-7) Expression
Time frame: 4 weeks
Change in Toll-like Receptor 8 (TLR-8) Expression
Time frame: 4 weeks
Change in Toll-like Receptor 9 (TLR-9) Expression
Time frame: 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Psoriasis
Not yet recruitingPhase 2
Extension Study of Safety and Tolerability of DDY391 in Participants With Moderate to Severe Psoriatic Arthritis (CDDY391A12201-extension)
Moderate to Severe Psoriatic Arthritis
Recruiting
Efficacy of a Self-Management Smartphone App to Improve Safety Skills in Patients With Inflammatory Arthritis
Rhumatoid Arthisis, Spondyloarthritis (SA)
Active, not recruitingPhase 2
Dose Ranging Study of ORKA-001 in Patients With Moderate-to-Severe Plaque Psoriasis
Plaque Psoriasis
RecruitingPhase 1
A Study of HB0017 Injection in Healthy Volunteers to Evaluate Safety and Tolerability of a Single Subcutaneous Injection in Low-Body-Weight Subjects; and Pharmacokinetics at Different Subcutaneous Injection Sites at the Same Dose
Psoriasis, Ankylosing Spondylitis
RecruitingPhase 1
A Study to Learn if Bimekizumab Given in Different Ways is Safe and Moves Similarly Throughout the Body Over Time in Adults
Psoriatic Arthritis, Axial Spondyloarthritis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tissa Hata, MD principal investigator
UCSD Division of Dermatology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hylenex and Normal Saline in people with Psoriasis, run by Tissa Hata, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Psoriasis Area Severity Index (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jan 2019.