Alefacept in Patients With Severe Scalp Alopecia Areata

Study Overview
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Brief Summary
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The purpose of this study is to examine prospectively the safety and efficacy of alefacept in the treatment of subjects with severe alopecia areata of the scalp. Common features between psoriasis and alopecia areata, including immunologic and therapeutic aspects, suggest that alefacept, which has been shown to be a safe and statistically significant beneficial therapeutic modality for the treatment of psoriasis, may have therapeutic value in alopecia areata.

Detailed Description
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Alopecia areata (AA) is an autoimmune condition characterised by a T-cell mediated attack on the hair follicle. The inciting antigenic stimulus is unknown. A dense peribulbar lymphocytic infiltrate and reproducible immunologic abnormalities are hallmark features of the condition. The cellular infiltrate primarily consists of activated T-lymphocytes and antigen-presenting Langerhans cells. T-lymphocytes play a critical role in the pathogenesis of disease. The observance of hair regrowth in those with alopecia areata who are treated with cyclosporine, a known inhibitor of T-cell function, further confirms the central role of the T-lymphocytes in the development of the disease. Activation of T-cells is initiated by interaction of the T-cell receptor with the antigen/major histocompatibility complex on the antigen-presenting cells. Co-stimulatory interactions occur secondarily, including binding of the T-cell CD2 receptor to the antigen-presenting cell ligand LFA-3 (lymphocyte function-associated antigen-3 CD58). Induction of a molecular signaling cascade with resultant T-cell activation and proliferation ensues. Abrogation of this activation may result in diminished or aborted expression of disease, and thus suggests a potential therapeutic role for alefacept in the treatment of alopecia areata. Alefacept is a bioengineered LFA-3/Immunoglobulin fusion protein that binds to the CD2 T-cell receptor and interferes with the ligation of LFA-3. Binding of the immunoglobulin portion of the fusion protein to the FCy receptor on antigen-presenting cells potentiates apoptosis of CD-2 T-cells to thereby reduce the population of activated T-cells. Psoriasis is a T-cell mediated disorder that shares many immunologic features with alopecia areata. Accordingly, treatments that are effective in psoriasis often prove to be beneficial in alopecia areata. Anthralin, topical and intralesional steroids and cyclosporine are among several therapeutic agents that have efficacy in both disorders. Based on the impressive therapeutic responses seen in those with psoriasis treated with alefacept, a similarly beneficial outcome is tentatively anticipated with treatment of those with alopecia areata.

Official Title
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A Double-Blind, Placebo-Controlled, Randomized, Multi-Center Study to Evaluate The Safety and Therapeutic Efficacy of Intramuscular Administration of Alefacept in Patients With Chronic, Severe Scalp Alopecia Areata

Conditions
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Alopecia Areata

Intervention / Treatment
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* Drug: Alefacept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must give written informed consent and candidates in the US must authorize the release and use of protected health information (PHI) Subjects must be between the ages of 18 and 65 inclusive at the time of informed consent Must have a diagnosis of scalp alopecia areata as determined by the study investigator Must have 50-95% patchy scalp hair loss due to alopecia areata of at least one year duration Must have CD4+ T-lymphocyte counts at or above the lower limit of normal as determined by a local laboratory. Exclusion Criteria: History of systemic or cutaneous malignancy other than treated basal cell carcinomas or 3 or less squamous cell carcinomas. Nevi or cutaneous lesions currently undiagnosed but suspicious for malignancy. Evidence of immunocompromise. Advanced or poorly controlled diabetes. Unstable cardiovascular disease. Clinically significant medical or psychiatric disease as determined by the investigator. History of alcohol or drug abuse within 2 years of assessment for study enrollment. Serious local infection (e.g. cellulitis, abscess) or systemic infection (e.g. pneumonia, septicemia) within 3 months prior to the first dose of investigational drug. Positive PPD history of incompletely treated or untreated tuberculosis. Abnormal T-lymphocyte count, and/or liver function tests. If female, serum hemoglobin level greater than 1 unit below accepted limit for normal or otherwise abnormal. Male subjects with an abnormal serum hemoglobin. Known positivity for hepatitis C antigen or hepatitis B surface antigen. Known positivity for HIV antibody. Diagnosis of diffuse alopecia areata. Coexistent androgenetic alopecia which, in males is Norwood-Hamilton stage VI or greater, or in females, Ludwig stage III. Prior treatment with alefacept. Treatment with another investigational drug within 4 weeks prior to anticipated first treatment dose. Unable to practice effective contraception for the duration of the study. Females who are nursing, pregnant or planning to become pregnant while in the study. Those who have donated blood within a month of date of screening evaluation. Concomitant enrollment in other investigational drug study. Unwilling to maintain a consistent hair style and to eschew shaving of scalp hair throughout the course of the study. Unable to comply with the protocol. Other unspecified reasons that contraindicate enrollment in the study, as determined by the study investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alefacept<br> | Drug: Alefacept<br>* Study participants will receive weekly IM administration of placebo or 15 mg of alefacept for 12 weeks, to be followed by a 12-week post-treatment period during which the safety, efficacy, and durability of effect in treatment responders will be assessed on weeks 2, 4, 8 and 12.<br>|
| Placebo Comparator: Placebo<br> | Drug: Alefacept<br>* Study participants will receive weekly IM administration of placebo or 15 mg of alefacept for 12 weeks, to be followed by a 12-week post-treatment period during which the safety, efficacy, and durability of effect in treatment responders will be assessed on weeks 2, 4, 8 and 12.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Subjects Achieving at Least a 50% Reduction in Their Scalp Alopecia Areata Severity Scores (SALT Score) From Baseline Values | Assess the therapeutic efficacy of a 12-week regimen of weekly IM administration of alefacept followed by a 12 week observation period in subjects with chronic severe scalp alopecia | 24 weeks | 
| Number of Adverse Events | Number of any adverse event reported throughout the study, regardless of relation to study drug | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alopecia Areata