Study To Evaluate The Efficacy Of Tofacitinib In Moderate To Severe Alopecia Areata, Totalis And Universalis
Condition: Alopecia Areata
MeSH terms: Alopecia; Alopecia Areata
Intervention: Tofacitinib
Intervention description: Dosage/Frequency: 5mg - 10mg, oral, twice daily
Intervention MeSH terms: Tofacitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Alopecia Areata

Summary:

      This is an open-label pilot study of tofacitinib taken daily for 6 months in the treatment of
      moderate to severe AA, and alopecia totalis or universalis, followed by 6 months follow-up
      off drug to assess the incidence and timing of recurrence of disease or documentation of
      delayed response to treatment. 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.
    

Eligibility criteria:

        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 CYP3A4 (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, diphenylcyclopropenone (DPCP), 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).