Study To Evaluate The Efficacy Of Tofacitinib In Moderate To Severe Alopecia Areata, Totalis And Universalis

Alopecia areata (AA) is a common disease of the immune system, known as an "autoimmune"
disease. In the 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 new,
better ways to treat AA has lagged far behind other similar diseases of the immune system.
Currently, there are no Federal Drug Administration approved drugs for AA.

Tofacitinib (made by Pfizer) is an intervention known to effectively treat a disease of the
joints, known as rheumatoid arthritis. It is also being studied in the treatment of
psoriasis, another "autoimmune" disease, by fighting inflammation. There are some genetic
and chemical similarities between those with active rheumatoid arthritis, psoriasis, and
AA,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 AA from starting in mice that would have otherwise developed the
disease. To test Tofacitinib, we are going to treat 15 patients with moderate to severe AA
for up to 6 months. This is an "open label" study, meaning that there will not be a placebo
group; all patients enrolled in the study will receive the active medication. 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. After the
treatment period of up to 6 months is completed, There will be the option of increasing the
treatment duration up to an additional 6 months beyond the initially scheduled 6 months of
treatment, if clinically indicated, and at the discretion of the investigator. 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. The safety of the medication, Tofacitinib, in patients with AA
will also be evaluated. Blood work will be collected before medication is started, during
the treatment period and after Tofacitinib is stopped in order to monitor for adverse
effects of the medication. Small scalp biopsies and peripheral blood will be taken at the
beginning of the study before treatment and at weeks 4 and 24. Additional, optional scalp
biopsies and blood draws may be suggested at other important time points. The chemical
analysis of these skin samples and blood will help us to understand how the disease happens,
how the treatment works, and even guide us to better treatments in the future.

Inclusion Criteria:

- Patients between 18 and 65 years of age.

- Patients with a diagnosis of moderate to severe patch type alopecia areata.

- Patients with alopecia totalis or universalis may be enrolled.

- Patients have >30% and <95% total scalp hair loss at baseline as measured using the
SALT score to qualify as moderate to severe patch type AA; and 95-100% scalp hair
loss to qualify as alopecia totalis or universalis.

- Duration of hair loss greater than 3 months without an upper limit of duration as
long as there is reason to believe that regrowth is possible in the opinion of the
investigator.

- No evidence of significant active ongoing regrowth present at baseline.

- Patients with a history of alopecia totalis/universalis can be included as long as
the current episode of hair loss meets the criteria of 30 to 95% hair loss (i.e. they
are not currently AT or AU), and as long as in the opinion of the investigator there
does appear to be potential for regrowth. Patients with current episodes of alopecia
totalis/universalis may be included in this study.

- Vaccinations should be up to date in agreement with current immunization guidelines
prior to start of tofacitinib. The patient will be asked to obtain verbal
verification from their primary care provider that this is the case.

- Patients may be naïve to treatment or unresponsive to intralesional (IL) steroids or
other treatments for alopecia areata.

- Women of childbearing potential (WOCBP) must use highly effective methods of birth
control [for at least 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.

1. 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.

2. Women must not be breastfeeding.

Exclusion Criteria:

- Sex and Reproductive Status

1. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy
for the entire study period and for up to 12 weeks after the last dose of study
drug.

2. WOCBP using a prohibited contraceptive method.

3. Women who are pregnant or breastfeeding.

4. Women with a positive pregnancy test on enrollment or before administration of
tofacitinib.

5. Sexually active fertile men not using effective birth control if their partners
are WOCBP.

- Target Disease Exceptions

1. Patients with current alopecia totalis/universalis (i.e. 100% scalp or 100%
scalp and body loss, respectively) may be enrolled.

2. Patients with a history of or active skin disease on the scalp such as psoriasis
or seborrheic dermatitis.

3. Patients in whom the diagnosis of alopecia areata is in question or in whom the
pattern of hair loss is such that quantification of hair loss and assessment of
regrowth is difficult. E.g patients with diffuse alopecia areata. This
assessment is at the investigator's discretion.

4. 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.

5. Patients with hemoglobin levels <9 g/dL, lymphocyte count <500 cells/mm3,
absolute neutrophil count (ANC) <1000 cells/mm3, at baseline.

6. Patients known to be HIV or hepatitis B or C positive.

7. Patients with history or evidence of moderate or severe hepatic and/or renal
impairment.

8. Patients with history of immunosuppression or history of recurrent serious
infections.

- Coexisting disease or concurrent medications

1. Patients taking potent inhibitors of Cytochrome P450 3A4 (e.g.ketoconazole).

2. Patients receiving one or more concomitant medications that result in both
moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (e.g.,
fluconazole).

3. Patients known to be HIV or hepatitis B or C positive.

4. Patients with evidence of infection or active/untreated skin cancer.

5. 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.

6. Patients who are impaired, incapacitated, or incapable of completing
study-related assessments.

7. Patients 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.

8. Female patients 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.

9. Patients with a history of cancer in the last 5 years, other than non-melanoma
skin cell cancers cured by local resection or carcinoma in situ. Existing
non-melanoma skin cell cancers should be removed, the lesion site healed, and
residual cancer ruled out before administration of the study drug.

10. Patients who currently abuse drugs or alcohol.

11. Patients 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.

12. Patients with herpes zoster or cytomegalovirus (CMV) that resolved less than 2
months before the informed consent document was signed.

13. Patients who have received any live vaccines within 3 months of the anticipated
first dose of study medication.

Subjects may not receive live vaccine concurrently with tofacitinib.

14. Patients with a history or symptoms suggestive of gastrointestinal perforation
or disorders that might increase the risk of GI perforation such as gastric
ulcers or diverticulitis.

15. Patients who take NSAIDs at high dose or on a frequent basis, which in the
investigator's opinion might increase the risks of gastrointestinal perforation.

16. Patients with any serious bacterial infection within the last 3 months, unless
treated and resolved with antibiotics, or any chronic bacterial infection (e.g.,
chronic pyelonephritis, osteomyelitis, or bronchiectasis).

17. Patients 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).