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
Intervention: Abatacept
Intervention description: 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.
Intervention MeSH terms: Abatacept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Alopecia Areata; AA

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed Written Informed Consent Before any study procedures are performed, subjects
             will have the details of the study described to them, and they will be given a written
             informed consent document to read. Then, if subjects consent to participate in the
             study, they will indicate that consent by signing and dating the informed consent
             document in the presence of study personnel.

          -  Must be between 18 and 75 years of age.

          -  Must have a diagnosis of moderate to severe AA - defined as the presence of equal to
             or more than 30% and equal to or less than 95% total scalp hair loss at baseline as
             measured using the SALT score. In addition, a few patients with 100% scalp hair loss
             will be enrolled.

          -  Duration of hair loss must be at least 3 months.

          -  There may be no evidence of regrowth present at baseline.

          -  Subjects may be naïve to treatment or unresponsive to intralesional (IL) steroids or
             other treatments for AA.

          -  Must be willing to avoid live vaccines while on the study medication, and within 3
             months of its discontinuation.

          -  Women of childbearing potential (WOCBP) must use highly effective methods of birth
             control [for up to 12 weeks after the last dose of investigational product] to
             minimize the risk of pregnancy]. WOCBP must follow instructions for birth control for
             the entire duration of the study including a minimum of 90 days after dosing has been
             completed.

        (Acceptable methods of highly effective birth control include: Condom with spermicide,
        Diaphragm and spermicide, Cervical cap and spermicide)

          -  The use of intrauterine devices, (IUDs) shall be at the discretion of the
             investigator.

          -  Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L
             or equivalent units of HCG) within 24 hours prior to the start of investigational
             product.

          -  Women must not be breastfeeding

          -  Sexually active fertile men must use highly effective birth control if their partners
             are WOCBP. Men that are sexually active with WOCBP must follow instructions for birth
             control for the entire duration of the study and a minimum of 90 days after dosing has
             been completed.

        Exclusion Criteria:

          -  Sex and Reproductive Status

          -  WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for
             the entire study period and for up to 10 weeks after the last dose of study drug.

          -  WOCBP using a prohibited contraceptive method.

          -  Women who are pregnant or breastfeeding.

          -  Women with a positive pregnancy test on enrollment or before administration of
             abatacept.

          -  Sexually active fertile men not using effective birth control if their partners are
             WOCBP.

          -  Patients with a history of or active skin disease on the scalp such as psoriasis or
             seborrheic dermatitis.

          -  Patients in whom the diagnosis of alopecia areata is in question.

          -  Patients with active medical conditions or malignancies (except adequately treated
             basal or squamous cell carcinoma) that in the opinion of the investigator would
             increase the risks associated with study participation, including patients with a
             history of recurrent infections.

          -  Patients with COPD

          -  Patients known to be HIV or hepatitis B or C positive.

          -  Patients with history or evidence of hematopoietic abnormality.

          -  Patients with history of immunosuppression or history of recurrent serious infections.

          -  Patients unwilling or unable to discontinue treatments known to affect hair regrowth
             in AA

          -  Coexisting disease or concurrent medications

          -  Patients taking TNF antagonists or other biological therapy such as anakinra.

          -  Patients with evidence of infection or active/untreated skin cancer.

          -  Patients who have been treated with intralesional steroids, systemic steroids,
             anthralin, squaric acid, DPCP (diphenylcycloprophenone), protopic, minoxidil or other
             medication which in the opinion of the investigator may affect hair regrowth within
             one month of the baseline visit.

          -  Subjects who are impaired, incapacitated, or incapable of completing study-related
             assessments.

          -  Subjects with current symptoms of severe, progressive, or uncontrolled renal, hepatic,
             hematologic, gastrointestinal, pulmonary, cardiac, neurologic, or cerebral disease,
             which, in the opinion of the investigator, might place a subject at unacceptable risk
             for participation in the study.

          -  Female subjects who have had a breast cancer screening that is suspicious for
             malignancy and in whom the possibility of malignancy cannot be reasonably excluded by
             additional clinical, laboratory, or other diagnostic evaluations.

          -  Subjects with a history of cancer in the last 5 years, other than non-melanoma skin
             cancers cured by local resection or carcinoma in situ. Existing non-melanoma skin
             cancers should be removed, the lesion site healed, and residual cancer ruled out
             before administration of the study drug.

          -  Subjects who currently abuse drugs or alcohol.

          -  Subjects with evidence (as assessed by the investigator) of active or latent bacterial
             or viral infections at the time of potential enrollment, including subjects with
             evidence of human immunodeficiency virus (HIV) detected during screening.

          -  Subjects with herpes zoster or cytomegalovirus (CMV) that resolved less than 2 months
             before the informed consent document was signed.

          -  Subjects who have received any live vaccines within 3 months of the anticipated first
             dose of study medication.

          -  Subjects with any serious bacterial infection within the last 3 months, unless treated
             and resolved with antibiotics, or any chronic bacterial infection (eg, chronic
             pyelonephritis, osteomyelitis, or bronchiectasis).

          -  Subjects at risk for tuberculosis (TB). Specifically excluded from this study will be
             subjects with a history of active TB within the last 3 years, even if it was treated;
             a history of active TB greater than 3 years ago, unless there is documentation that
             the prior anti-TB treatment was appropriate in duration and type; current clinical,
             radiographic, or laboratory evidence of active TB; and latent TB that was not
             successfully treated (≥ 4 weeks).

          -  Subjects known to be positive for HIV, hepatitis B or C.

          -  Subjects who are positive for hepatitis C antibody if the presence of hepatitis C
             virus was also shown with polymerase chain reaction or recombinant immunoblot assay.

          -  Subjects with any of the following laboratory values Hemoglobin < 10.0 g/dL WBC <
             3500/mm3 (< 3 x 109/L) Platelets < 120,000/mm3 (< 3 x 109/L) Serum creatinine > 2
             times the ULN Serum ALT or AST > 2 times the ULN

          -  Any other laboratory test results that, in the opinion of the investigator, might
             place a subject at unacceptable risk for participation in the study.

        PROHIBITED TREATMENTS AND/OR THERAPIES:

          -  Subjects who have at any time received treatment with any investigational drug within
             28 days (or less than 5 terminal half-lives of elimination) of the Day 1 dose.

          -  Any concomitant biologic DMARD, such as anakinra.

          -  Subjects who have been treated with intralesional steroids, systemic steroids,
             anthralin, squaric acid, DPCP (diphenylcycloprophenone), protopic, minoxidil or other
             medication which in the opinion of the investigator may affect hair regrowth within
             one month of the baseline visit.

        OTHER EXCLUSION CRITERIA

          -  Prisoners or subjects who are involuntarily incarcerated.

          -  Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (eg, infectious disease) illness.