An Open-Label Single-Arm Clinical Trial to Evaluate The Efficacy of Abatacept in Moderate to Severe Patch Type Alopecia Areata

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.

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.