Alefacept in Patients With Severe Scalp Alopecia Areata
Condition: Alopecia Areata
MeSH terms: Alopecia; Alopecia Areata
Study type: Interventional

Summary: 
      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: 
      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.
    

Intervention name(s): Alefacept
Intervention type(s): Drug
Intervention description(s): 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.
Intervention MeSH terms: Alefacept
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Other
Keywords: Alopecia Areata