An Open-Label Single-Arm Clinical Trial to Evaluate The Efficacy of Abatacept in Moderate to Severe Patch Type Alopecia Areata
Condition: Alopecia Areata
MeSH terms: Alopecia; Alopecia Areata
Study type: Interventional
Phase: Phase 2

Summary: 
      Alopecia areata (AA) is a common disease of the immune system, known as an "autoimmune"
      disease. In this disease, the immune system mistakenly destroys the hair follicle, causing
      hair to fall out. Despite many people having this disease, research into its cause and into
      new, better ways to treat Alopecia Areata has lagged far behind other similar diseases of the
      immune system. Currently, there are no Federal Drug Administration approved drugs for
      Alopecia Areata.

      Abatacept (made by Bristol-Myers Squibb) is a safe intervention known to effectively treat
      rheumatoid arthritis, another "autoimmune" disease, by fighting inflammation. There are some
      genetic and chemical similarities between those with active rheumatoid arthritis and Alopecia
      Areata, suggesting that treatment with the same drug is likely to be effective. In mice
      specially designed for testing drugs for the treatment of human alopecia, this medication
      worked to prevent the disease Alopecia Areata from starting.

      To test Abatacept, we are going to treat 15 patients with moderate to severe Alopecia Areata
      for 6 months. Each person enrolling into this study will receive the active study drug. The
      effectiveness of the medication will be measured by changes in hair re-growth as determined
      by physical exam and photography, as well as by patient and physician scoring. Patients will
      be followed for another 6 months off of the drug to see if the effects of treatment last and
      if there is delayed response. We have recently changed the study to allow testing of
      abatacept in a few patients with alopecia totalis and universalis.

      Small scalp biopsies and peripheral blood will be taken at the beginning of the study before
      treatment and then after 4,12 and 24 weeks. The chemical analysis of these skin samples and
      blood will help us to understand how the disease happens, how the treatment works, and
      perhaps even guide us to better treatments in the future.
    

Detailed description: 
      Among patients with alopecia areata, patients with higher disease burdens are unlikely to
      have satisfactory outcomes with current therapies. Our hypothesis is that CTLA4-Ig will be
      effective therapy in moderate-severe alopecia areata by blocking re-activation of CD8+ memory
      T cells, thereby aborting the cytotoxic T cell inflammatory response underlying alopecia
      areata.

      Alopecia areata (AA) is a common autoimmune disease resulting from immune destruction of the
      hair follicle and subsequent hair loss. Despite its high prevalence, research into the
      pathogenesis and the development of innovative therapies in Alopecia Areata has lagged far
      behind other autoimmune diseases. Currently, there are no FDA approved drugs for Alopecia
      Areata. Abatacept is a safe intervention known to block costimulation and inflammatory
      responses in rheumatoid arthritis, which shares several susceptibility genes in common with
      Alopecia Areata. Both diseases share the involvement of CTLA4, which is the rationale for
      selecting Abatacept for evaluation in this clinical trial. CTLA4-Ig has been shown to prevent
      the onset of Alopecia Areata in the C3H-HeJ animal model of Alopecia Areata, demonstrating
      preclinical proof of concept data in Alopecia Areata.

      We will conduct an open label pilot study of 15 patients with moderate to severe Alopecia
      Areata treated with SC abatacept 125mg once per week for 6 months. A few subjects with
      alopecia totalis or universalis will also be included. Subjects will be followed for another
      6 months to evaluate durability of response following the treatment phase. The primary
      efficacy outcome will be the proportion of responders after 6 months of treatment compared to
      the historically known rate of response in untreated/placebo-treated subjects of 8 to 10%.
      Punch biopsies and peripheral blood will be obtained at baseline prior to treatment and then
      after 4, 12 and 24 weeks for immunomonitoring and molecular studies.

      The safety of and incidence of adverse events related to abatacept in this population of
      patients will also be analyzed as a secondary endpoint.
    

Intervention name(s): Abatacept
Intervention type(s): Drug
Intervention description(s): After the screening period, subjects will begin weekly self-administered subcutaneous abatacept and will continue treatment for 6 months. Patients will be instructed in self-administration of study medication at baseline (week zero) and will be observed self-administering medication at each visit. Instructions regarding study drug administration will be reinforced as needed.
The 6-month treatment period is expected to provide adequate time to assess the short-term efficacy and safety of abatacept in patients with moderate to severe AAP. Responders will then be followed for 6 months off drug.
Other intervention name(s): Orencia
Intervention MeSH terms: Abatacept
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Alopecia Areata; AA