Pilot Study of the Safety and Efficacy of Apremilast in Subjects With Moderate to Severe Alopecia Areata

This is a randomized, double-blind, placebo-controlled pilot study consisting of two phases.
A total of 30 subjects with moderate to severe alopecia areata (including universalis and
totalis) involving 50-100% of the scalp will be enrolled. A possible maximum of 15 patients
(approximately 7 patients each) with current episodes of AA totalis / universalis may be
included in this study.

In Phase 1, subjects will be randomized (2:1) to either receive apremilast or placebo for 24
weeks.

In Phase 2, eligible subjects will receive apremilast from Week 24 through Week 48. The
following subjects will be eligible to enter into Phase 2:

1. Subjects who received placebo in Phase 1 of the study

2. Subjects who received apremilast in Phase 1 of the study, and who achieved a minimum of
50% regrowth (SALT50) at Week 24, compared to Baseline.

Inclusion Criteria:

Males or females, 18 years or older at the time of signing the informed consent document.

Understand and voluntarily sign an informed consent document prior to any study-related
assessments/procedures are conducted.

Able to adhere to the study visit schedule and other protocol requirements. Subject with a
diagnosis of patchy scalp alopecia areata present for at least 6 months, and up to a
maximum of 10 years.

Patients with ≥50% and <95% total scalp hair loss at Baseline as measured using the SALT
score to qualify as moderate to severe AA; and 95%-100% scalp hair loss to qualify as AA
totalis/universalis.

Must meet the following laboratory criteria White blood cell count ≥ 3000/mm3 (≥ 3.0 x
109/L) and < 14,000/mm3 (< 14 x 109/L). Platelet count ≥ 100,000/μL (≥ 100 x 109/L). Serum
creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L). AST (SGOT) and ALT (SGPT) ≤ 2 x upper limit of
normal (ULN). If the initial test shows ALT or AST > 2 times the ULN, one repeat test is
allowed during the Screening Phase.

Total bilirubin ≤ 2 mg/dL (34 μmol/L). If the initial test shows total bilirubin > 2 mg/dL
(34 μmol/L), one repeat test is allowed during the Screening Phase.

Hemoglobin ≥ 10 g/dL (≥ 6.2 mmol/L).

Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening
and Baseline. While on investigational product and for at least 28 days after taking the
last dose of investigational product (IP), FCBP who engage in activity in which conception
is possible must use one of the approved contraceptive options described below:

Option 1: Any one of the following highly effective methods: hormonal contraception (oral,
injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal
ligation; or partner's vasectomy;

OR

Option 2: Male or female condom (latex condom or nonlatex condom NOT made out of natural
[animal] membrane [for example, polyurethane]); plus spermicide PLUS one additional barrier
method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c)
contraceptive sponge with spermicide.

Male subjects (including those who have had a vasectomy) who engage in activity in which
conception is possible must use barrier contraception (male latex condom or nonlatex condom
NOT made out of natural [animal] membrane [for example, polyurethane]) while on IP and for
at least 28 days after the last dose of IP.

No evidence of hair regrowth present at Baseline.

EXCLUSION CRITERIA:

The presence of any of the following will exclude a subject from enrollment:

Clinically significant (as determined by the investigator) cardiac, endocrine, pulmonary,
neurologic, psychiatric, hepatic, renal, hematologic, or immunologic disease, or other
major uncontrolled diseases that will affect the health of the subject during the study or
interfere with the interpretation of study results.

Hepatitis B surface antigen positive at Screening (Visit 1). Hepatitis C antibody positive
at Screening (Visit 1). History of positive human immunodeficiency virus (HIV), or
congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency [CVID]).
Subjects deemed at risk by the study investigator, may also undergo testing for human
immunodeficiency virus (HIV). Subjects deemed at risk include those with a history of
injection drug use, homosexual subjects, and subjects with known sexual contact with an HIV
positive partner.

Active TB or a history of inadequately treated TB. Active substance abuse or a history of
substance abuse within six months prior to Screening.

Pregnant or breast feeding. History of allergy to any component of the IP.

Major surgery within eight weeks prior to Screening (Visit 1) and/or planned surgery during
the length of the study.

Malignancy or history of malignancy, except for:

treated (ie, cured) basal cell or squamous cell in situ skin carcinomas; treated (ie,
cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix with no
evidence of recurrence within 5 years prior to Screening (Visit 1).

Unstable asthma (eg, acute episodes of exacerbation [nocturnal episodes, sudden episodes
triggered by unidentifiable factors] despite a stable regimen of anti-asthmatic
medications); prior episode(s) of life-threatening asthma; or asthma that requires inhaled
budesonide or equivalent at >1200 μg/day or fluticasone propionate at > 880 μg/day along
with another anti-asthmatic drug such as a long-acting beta-agonist.

A history of and/or concurrent condition of serious hypersensitivity (eg, anaphylaxis) to
drugs, foods, or other allergens without access to emergency rescue medication such as
epinephrine.

Persistent or recurring bacterial infection requiring systemic antibiotics, or clinically
significant viral or fungal infections, within two weeks of Screening (Visit 1). Any
treatment for such infections must have been completed at least two weeks prior to the
Screening Visit and no new/recurrent infections should have occurred prior to the Baseline
Visit.

Active skin infection requiring systemic antimicrobials at Baseline/Randomization (Visit
2).

Skin lesion(s) due to conditions other than AA that would interfere with the study
specified assessments.

Prior treatment with apremilast, or participation in a clinical study involving apremilast.

Use of phototherapy (ie, UVB, UVA) or systemic immunosuppressive drugs (including, but not
limited to, cyclosporine, corticosteroids, mycophenolate mofetil, azathioprine,
Methotrexate, or tacrolimus), or oral preparations of herbal immunomodulatory medications
within four weeks prior to Baseline/Randomization (Visit 2).

Use of interferon-γ within 12 weeks prior to Baseline/Randomization (Visit 2). Use of
abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, or
tocilizumab within 12 weeks prior to Baseline/Randomization (Visit 2).

Use of oral janus kinase (JAK) inhibitors (e.g. tofacitinib, ruxolitinib) within 12 weeks
prior to Baseline/Randomization (Visit 2).

Use of omalizumab, rituximab, ustekinumab, alefacept, briakinumab, or other therapeutic
antibody products within 24 weeks prior to Baseline/Randomization (Visit 2).

Use of any investigational drug within four weeks or five PK or PD half lives (whichever is
longer) prior to Baseline/Randomization (Visit 2).

Use of topical corticosteroid preparations, topical calcineurin inhibitors, or other
topical preparations with immunomodulatory properties within 2 weeks prior to
Baseline/Randomization (Visit 2).

Prior history of suicide attempt at any time in the subject's lifetime prior to Baseline
(Visit 2) or major psychiatric illness requiring hospitalization within 3 years prior to
Baseline (Visit 2).

History of male or female pattern hair loss Ludwig stage III or Hamilton > stage V.

Patients in whom the diagnosis of alopecia areata is in question, or subjects with scarring
alopecia.