Apremilast and Moderate to Severe Chronic Hand Dermatitis

Hand dermatitis is one of the most common skin disorders encountered by dermatologists.
Chronic hand dermatitis (CHD) is often due to allergic contact dermatitis (ACD) or irritant
contact dermatitis (ICD) and has a 1-year and lifetime prevalence of up to 10% and 15%,
respectively, in the general population. On average, the disease affects patients for about 7
to 11 years.

Patients with ACD show an increase in cytokines produced from T helper (Th)1 and Th17 cells,
including (interleukin) IL-17 and IL-23, which are also implicated in the pathogenesis of
psoriasis. Apremilast, a small molecule phosphodiesterase-4 (PDE-4) inhibitor, has
demonstrated clinical efficacy and tolerability in the treatment of psoriasis and psoriatic
arthritis, likely through the blockade of IL-17, IL-23, and several other pro-inflammatory
mediators. Therefore, it may provide an effective treatment option for other Th1 and
Th17-mediated disease (such as CHD due to ACD and ICD), which share a common immunologic
pathway with psoriasis. Investigators hypothesize that apremilast has the ability to decrease
disease severity in patients with moderate-to-severe CHD that is either secondary to
psoriasis, or occurring in patients with an atopic or allergic past medical history. Hence,
investigators have designed a pilot study involving CHD patients who attend the dermatology
clinic at the George Washington Medical Faculty Associates (GW MFA) in order to assess the
efficacy and safety of apremilast treatment for the treatment of moderate to severe CHD. The
objectives are as follows:

Primary objective:

1. To evaluate the efficacy of Apremilast 30mg twice daily administered as monotherapy in the
treatment of moderate-to-severe CHD as assessed by improvement of the Physician Global
Assessment (PGA).

Secondary objectives:

1. To evaluate the safety and tolerability of Apremilast 30mg twice daily as assessed by
monitoring adverse events, laboratory values (CBC, CMP), and physical examination.

2. To evaluate CHD lesion time to response (TTR) as assessed by Modified Total Lesion
Symptom Score (mTLSS).

3. To evaluate the patient's perception of CHD severity improvement as assessed by the
Patient Global Assessment (PaGA).

4. To evaluate the patient's health-related quality of life as assessed by the Dermatology
Life Quality Index (DLQI) questionnaire a measurement of the patient's subjective
symptoms.

STUDY ENDPOINTS

Primary endpoint:

1. Proportion of patients achieving a 2 point decrease in Physician Global Assessment (PGA)
at the end of the study.

Secondary endpoints:

1. Proportion of patients achieving Physician Global Assessment (PGA) score of 0 (clear) or
1 (almost clear) at end of study.

2. Change in mTLSS, patient global assessment, and DLQI scores from baseline to end of
study.

3. Photographic improvement of CHD from baseline to end of study.

Inclusion Criteria:

1. Adults between the ages of 18-79 years.

2. Must be in general good health (except for disease under study) as judged by the
Investigator, based on medical history, physical examination, clinical laboratories,
and urinalysis. (NOTE: The definition of good health means a subject does not have
uncontrolled significant co-morbid conditions).

3. Clinical diagnosis of CHD as defined by hand dermatitis for more than 6 months or more
than 2 flares within 12 months.

4. Moderate to severe CHD, defined as a PGA score of 3 (moderate) or 4 (severe).

5. History of AD, childhood eczema, ACD, or ICD.

6. History of disease that is unresponsive to conventional treatment (i.e.
corticosteroids, calcineurin inhibitors, phototherapy) for CHD. Lack of response to
treatment is defined as an unsatisfactory outcome (no response, transient response to
ongoing treatment or lack of tolerability) based on patient history and medical
records.

7. No other active skin diseases or acute skin infections dominating the clinical
picture.

8. 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, 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 one additional barrier method: (a)
diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge
with spermicide.

† A female of childbearing potential is a sexually mature female who 1) has not undergone a
hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical
removal of both ovaries) or 2) has not been postmenopausal for at least 24 consecutive
months (that is, has had menses at any time during the preceding 24 consecutive months).

§ The female subject's chosen form of contraception must be effective by the time the
female subject is randomized into the study (for example, hormonal contraception should be
initiated at least 28 days before randomization).

Exclusion Criteria:

1. <18 or >79 years of age.

2. Evidence of tinea mannum involving the hands (verified by positive fungal culture).

3. Evidence of an active untreated infection (bacterial, fungal, viral etc) involving the
hands at baseline visit.

4. Use of topical corticosteroids on the hands within 2 weeks prior to baseline visit.

5. Use of topical calcineurin inhibitor (tacrolimus, pimecrolimus) on the hands within 2
weeks prior to baseline visit.

6. Use of crisaborole on the hands within 2 weeks prior to baseline visit.

7. Use of light based treatments on the hands within 1 month prior to baseline visit.

8. Use of systemic therapy (cyclosporine, azathioprine, methotrexate, alitretinoin)
within 4 weeks prior to the start of study medication OR 5 pharmacokinetic /
pharmacodynamics half-lives (whichever is longer).

9. Inability to make study visits or anticipated poor compliance.

10. Pregnant females or nursing mothers. Eligible women of reproductive age will be
required to adhere to strict pregnancy prevention measures, which includes a negative
urine pregnancy test at screening and subsequent visits.

11. History of Tuberculosis, Hepatitis B, C, or HIV.

12. Any history or evidence of a medical comorbidity that would make the subject, in the
opinion of the investigator, unsuitable for the study.

13. Active substance abuse or a history of substance abuse within 6 months prior to
Screening.

14. Other than disease under study, any clinically significant (as determined by the
Investigator) cardiac, endocrinology, pulmonary, neurologic, psychiatric, hepatic,
renal, hematologic, immunologic disease, or other major disease that is currently
uncontrolled.

15. Life threatening illness that would interfere with the subject's ability to complete
the study.

16. Any condition, including the presence of laboratory abnormalities, which would place
the subject at unacceptable risk if he/she were to participate in the study.

17. Prior history of suicide attempt at any time in the subject's life time prior to
screening or randomization, or major psychiatric illness requiring hospitalization
within the last 3 years.

18. Malignancy or history of malignancy, except for:

1. Treated [i.e., cured] basal cell or squamous cell carcinomas of the skin with no
evidence of recurrence within the previous 5 years.

2. Treated [i.e., cured] cervical intraepithelial neoplasia (CIN) or carcinoma in
situ of cervix with no evidence of recurrence within the previous 5 years.

19. Use of any investigational drug within 4 weeks prior to randomization, or 5
pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).

20. Prior treatment with apremilast.