Topical Ruxolitinib for the Treatment of Vitiligo

The hypothesis is that JAK inhibitors can also successfully treat vitiligo. Lesional skin of
both alopecia areata and vitiligo primarily contain T cells in a TH1 response as opposed to a
mixed cell infiltrate such as in psoriasis or lichen planus. Both alopecia areata and
vitiligo are TH1 mediated diseases dependent on the production of IFN-gamma to drive the
response. CD8+ T cells are both necessary and sufficient for melanocyte destruction in
vitiligo (van den Boorn JG et al 2009) and CD8+NKG2D+ T cells are also necessary and
sufficient for hair loss in alopecia areata (Gilhar A et al 2013).

Inclusion Criteria:

- Clinical diagnosis of vitiligo.

- At Visit 1 (Baseline/Day 1), have had vitiligo covering at least 1% of total body
surface area (BSA) on the scalp, trunk or limbs (excluding nails).

- Female subjects of childbearing potential must agree to use a highly effective method
of contraception throughout the study and for at least four weeks after the last dose
of assigned treatment. Male subjects must also use contraception, such as barrier
method with spermicide.

- If receiving concomitant medications for any reason, must be on a stable regimen and
willing to stay on a stable regimen.

- Must be willing to washout of other vitiligo treatments. All treatments for vitiligo
are prohibited during the course of the study.

Exclusion Criteria:

- Other skin conditions at Baseline that would interfere with evaluation of vitiligo.

- Pregnant/breastfeeding females, or females of childbearing potential not using highly
effective contraception. Women of childbearing potential must test negative for
pregnancy and use contraception for at least four weeks after last dose of drug.

- Current or recent history of clinically significant medical/psychiatric condition or
laboratory abnormality that may increase risk associated with the study participation
or drug administration.

- Have a history of any lymphoproliferative disorder, lymphoma, leukemia, history of
disseminated herpes zoster or disseminated herpes simplex, or a recurrent localized,
dermatomal herpes zoster.

- Have a history of infection requiring parenteral or oral or topical antimicrobial
therapy within 2 weeks prior to Baseline.

- Vaccinated with live/attenuated live vaccine within 6 weeks prior to Baseline.

- Previously participated in study of oral/topical ruxolitinib or tofacitinib
(tofacitinib, CP-690,550, formerly tasocitinib) unless confirmed to have been
randomized to and treated with placebo or placebo topical formulation (vehicle) only.

- Received a prohibited concomitant medication within 7 days or 5 half-lives (whichever
is longer) prior to Baseline.

- Have participated in other studies within 4 weeks or 5 half-lives (whichever is
longer) prior to Visit 1 (Baseline/Day 1). Subjects cannot participate in studies of
other investigational or experimental therapies or procedures at any time during their
participation in this study.

- Subjects who are investigational site staff members or relatives of those site staff
members or subjects who are Sponsor employees directly involved in the conduct of the
trial.

- In the opinion of the investigator or Sponsor, the subject is inappropriate for entry
into this study, or unwilling/unable to comply with study procedures and lifestyle
guidelines.

- Screening laboratory abnormalities

- CYP Inhibitor Exclusion: Subjects taking potent CYP3A4 inhibitors or fluconazole
within 2 weeks or 5 half-lives, whichever is longer, before the baseline visit.