Study of the Drug Efalizumab (Raptiva), for Adult Patients With Moderate to Severe Plaque Psoriasis

Study Overview
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Brief Summary
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Our laboratory is studying a skin disease known as psoriasis. The purpose of this protocol is to study the action and the effects of Efalizumab, on psoriasis. This medication has been studied extensively and has been found to be effective and safe in the treatment of psoriasis. The eligible patient will have 10% of his/her body surface area involved with psoriasis vulgaris.

Detailed Description
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The eligible patient will receive the drug Efalizumab, weekly for 12 weeks, by injection. The patient will be seen weekly for 12 weeks and every other week for the 12 weeks of follow up. At those visits, the patient can expect that a physical and skin exam will be done. At specific weeks, blood work will be drawn, clinical photography taken and a skin biopsy done. Two types of skin biopsies will be done after local anesthesia has been administered. One is a punch biopsy where a small piece of skin will be taken, the approximate size of a pencil eraser. The second type of skin biopsy is shave biopsy, where a postage sized piece of skin will be taken.

Official Title
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A Phase IIIB Study to Evaluate the Mechanism of Action of 1.0 mg/kg Subcutaneously Administered Efalizumab in Adults With Moderate to Severe Plaque Psoriasis Who Are Candidates for Systemic Therapy

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Efalizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Plaque psoriasis covering >10% of total BSA Diagnosis of plaque psoriasis for at least 6 months PASI score >=12 (see Appendix A) or Linear PASI score of >= 8.0 at screening (see Appendix B) In the opinion of the investigator, candidate for systemic therapy for psoriasis: Who has not been previously treated (naive to systemic treatment) OR Who has had prior treatment with systemic therapy for psoriasis (e.g., PUVA, cyclosporine, corticosteroids, methotrexate, oral retinoids, mycophenolate mofetil (MMF), thioguanine, hydroxyurea, sirolimus, azathioprine, 6-MP, etanercept) Body weight of <140 kg 18 to 75 years old. As the risk of Efalizumab in childhood is unknown, those < 18years will be excluded from the study For women of childbearing potential or in men whose partners may become pregnant, willingness to use an acceptable method of contraception to prevent pregnancy for the duration of the study (while receiving study medication and 3 months following). Acceptable methods of contraception include use of a condom; abstinence; use by sexual partner of oral implantable or injectable contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap; or a sterile sexual partner Willingness to hold sun exposure reasonably constant and to avoid use of tanning booths or other UV light sources during the study Exclusion Criteria Subjects who meet any of the following exclusion criteria are ineligible for study entry: Guttate, erythrodermic, or pustular psoriasis as sole or predominant form of psoriasis History of severe allergic or anaphylactic reactions to humanized monoclonal antibodies or fusion proteins that contain an Ig Fc region Clinically significant psoriasis flare during screening or on the first treatment day Treatment with efalizumab (anti-CD11a) within the last 12 months before enrollment Pregnancy or lactation. As the risk of Efalizumab in pregnancy is unknown, pregnant women will be excluded from the study History of or ongoing uncontrolled bacterial, viral, fungal, or atypical mycobacterial infection History of active tuberculosis (TB) or currently undergoing treatment for TB. PPD testing or chest X-ray is required for high-risk subjects (see Appendix D). Subjects with a positive PPD (not due to BCG vaccination) or chest X-ray will be excluded History of opportunistic infections (e.g., systemic fungal infections, parasites) Seropositivity for human immunodeficiency virus (HIV) Seropositivity for hepatitis B or C virus Hepatic enzymes >3 times the upper limits of normal (ULN) Diagnosis of hepatic cirrhosis, regardless of cause or severity WBC count <4000μL or >14,000/μL Serum creatinine >2 times the ULN Hospital admission for cardiac disease, stroke, or pulmonary disease within the last year Presence of malignancy within the past 5 years, including lymphoproliferative disorders. Subjects with a history of fully resolved basal cell or squamous cell skin cancer may be enrolled History of substance abuse within the last 5 years Any medical condition that, in the judgment of the investigator, would jeopardize the subject's safety following exposure to study drug Note: Certain medications and vaccines may not be used for specified periods of time prior to enrollment or at any time during the treatment period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: psoriasis<br>moderate to severe plaque psoriasis | Drug: Efalizumab<br>* 24 weekly doses of 1.0 mg/kg Efalizumab. Study drug will be administered by SC injection<br>* Other names: Raptiva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Improvement of Target Lesions | a single composite score based on quantitative measurement of epidermal acanthosis, qualitative expression of Keratin16 (histochemistry assessment) and quantitative measurement of K16 mRNA. | week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Overall Clinical Response as Measured by Psoriasis Area and Severity Index (PASI) | Psoriasis Area and Severity Index (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). Clinical response defined as PASI improvement over 75% at week 12. | Day 0, day 14, day 42, day 84, Days 112, 140, and 168. PASI has been measured at those timepoints but outcome is related to Baseline and Day 84. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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skin, psoriasis