DPCP for the Treatment of Alopecia Areata

This is an open labeled study to determine the response and characteristics, safety and
efficacy, of the proprietary DPCP ointment composition as a topical immunotherapeutic agent
for the treatment of extensive alopecia areata.

Up to 10 subjects with 76% to 99% scalp hair loss that, in the opinion of the PI, are
eligible for treatment with DPCP will be enrolled. Patients will be recruited from the new
and current patient population seen for alopecia areata through the University of Minnesota
Medical Center Dermatology Clinic as well as through partnership with the National Alopecia
Areata Foundation Clinical Trials Network, and various media outlets.

The products to be evaluated are as follows:

- 0.05 mL of 0.4% DPCP (sensitization dose) applied topically to the inner aspect of the
upper right arm. ("Sensitization and Baseline Sample Collection Visit")

- 0.05 mL four dose concentration matrix of DPCP ointment (0.1, 0.05, 0.01, 0.005%)
prepared through dilutions in a non-volatile vehicle (applied to the inner aspect of the
left upper thigh). ("Dose Determination Visit"; 10-14 days after the Sensitization
Visit)If sensitization is not attained after 10 to 14 days, the procedure will be
repeated once.

The subject will return 2 days after the Dose Determination Visit, so the PI or co-PI can
assess the dose concentration matrix. The weakest strength concentration that caused a
minimal reaction will be used throughout the study. 0.75-1 g of the treatment drug will be
aThe treatment drug will be applied by the PI, a trained study coordinator, or a staff member
of the Clinical Research Unit at the University of Minnesota. Eligible subjects may begin
receiving the study drug immediately after enrollment and screening.

The estimated duration of the study is 22 weeks. See Appendix A for the schedule of visits.
There will be a total of 42 visits, beginning with a screening visit followed by a single
sensitizing dose of study drug at baseline (Day -16) and a dose determination application at
Day -2.

Subjects will undergo twice weekly (+/- 2 days) topical applications of an ointment
formulation of DPCP during Weeks 1-18. Application will be done twice per week. The drug
application will be performed by a board certified dermatologist for the first two treatment
visits (Days 0 and 3; Visits 4 and 5), after which a trained member of the Clinical Research
Unit staff will apply the drug twice each week (Weeks 2-18; Visits 6-39). The investigator
will attend one treatment visit in the Clinical Research Unit each month to evaluate the
extent of hair loss and hair growth (Weeks 4, 8, 12, and 16).

Scalp biopsy specimen collection will be performed at baseline (Day -16, Visit 2), three days
after the first treatment (i.e., challenge) application (Day 2, Visit 5), three days after
the final application (Week 18 +3d, Visit 39) or during treatment when the study subject is
determined to have achieved >=50% hair regrowth.

Three scalp biopsy samples will be collected by a board certified dermatologist. When
possible, each sample will be taken from a balding area near an area with hair preferably in
a non-androgen dependent site of the scalp. One of the three samples will be frozen in OCT
for histologic examination and immunohistochemical studies. A second biopsy sample from an
adjacent area will be placed in 10% buffered formalin for histologic examination and
assessment of inflammation and hair follicle differentiation. The third sample from each area
will immediately be placed in RNAlater (Qiagen, Valencia, CA) for cytokine expression
analyses.

Peripheral blood collection for the study will include whole blood for serum and obtaining
peripheral blood mononuclear cells (PBMCs). All blood samples will be transported to the
Dermatology laboratory at the University of Minnesota for immediate processing and storage
for additional biomarker studies.

Research coordinators will be involved in patient recruitment, contact, and scheduling. The
PI and research coordinators will all be involved in the collection, analysis, and reporting
of collected data.

applied in a thin film that covers the entire scalp.

Inclusion Criteria:

1. Subject has clinical diagnosis of extensive alopecia areata (76%-99% involvement as
determined by SALT score, Appendix B, Part I).

2. Written informed consent and HIPAA authorization have been obtained.

3. Subject is > 18 to years of age.

4. Female subjects of childbearing potential have a negative pregnancy test and agree to
use an acceptable, highly effective method of birth control (i.e., failure rate of
less than 1% per year) to prevent pregnancy.

5. Subject agrees to comply with protocol requirements and attend all required study
visits and is considered to be a good study subject.

6. Subject meets concomitant medication washout requirements

Exclusion Criteria:

1. Subject has <76 or greater than 99% hair loss.

2. Subject is pregnant or lactating.

3. Subject has current controlled or uncontrolled bacterial, viral (with the exception of
herpes simplex), fungal, atypical, or opportunistic infection(s).

4. Subject has a history of substance abuse within the past five years.

5. Immunosuppression (history of transplantation, chemotherapy, splenectomy, HIV).

6. Administration of systemic treatment (e.g., Imuran, biologics) that have an
immunomodulatory mechanism of action in the preceding 3 months.

7. Previous treatment with DPCP.

8. Application of topical immunomodulating agent in the preceding 6 weeks.

9. Application of topical or intralesional corticosteroids within the past 6 weeks.

10. Systemic (oral, inhaled, or intravenous) administration of corticosteroid or other
systemic treatment (i.e., prednisone) with an immunosuppressive mechanism of action
within the past 3 months.

11. Use of light treatments (e.g., PUVA, narrow band UVB) in the preceding 6 weeks.

12. Use of Anthralin in preceding 6 weeks.

13. Use of minoxidil, topical or oral, in the preceding 4 weeks.

14. Subject is currently or has undergone systemic therapy for malignancy within the past
five years except for adequately treated Squamous Cell Carcinoma (SCC) or Basal Cell
Carcinoma (BCC) of the skin.

15. Clinical evidence of secondary skin infection (i.e., folliculitis).

16. Participation in other therapeutic investigational clinical trials within 4 weeks of
enrollment.

17. Evidence of anemia, thyroid disease, sarcoidosis or other medical condition that could
be adversely affected by participating in the study.

18. Subject has any medical condition that, in the judgment of the Investigator, would
jeopardize the subject's safety following exposure to the administered medications.