An Investigator Initiated Open Label Study Evaluating the Efficacy and Tolerability of Oral Apremilast for the Treatment of Nail Psoriasis

Psoriasis vulgaris is a common inflammatory condition of the skin that results in scaly red
itchy plaques. In addition to affecting the skin, psoriasis can also cause disease in the
finger and toe nails. Nail psoriasis is a chronic disease and can present with the following
clinical findings: splinter hemorrhage, leukonychia, red spots in the lunula, nail pitting,
nail plate crumbling, hyperkeratosis, and/or nail plate separation from the nail bed. The
most characteristic nail findings associated with nail psoriasis are nail pitting,
onycholysis with a rim of erythema, and oil spots. Special interest will be paid to
identifying these particular nail findings in patients, however all potential nail psoriasis
symptoms will be assessed in patients in this study. Due to the highly visible nature of
disease in the fingernails, nail psoriasis often results in a substantial deleterious effect
on a patient's quality of life. Patients also can have significant pain and disability due to
nail psoriasis.

Psoriasis patients who have nail involvement are known to have more severe psoriasis disease
and diminished quality of life when compared to psoriasis patients without nail disease.
Patients with nail psoriasis often also have psoriatic arthritis, and untreated psoriatic
arthritis is known to lead to joint destruction with potentially severe morbidity. Nail
psoriasis has a reported incidence of 80 to 90% (Jiaravuthiasan, et al). Because nail
psoriasis causes a substantial disease burden for patients, it is critical that safe and
effective treatments are found for this specific type of psoriasis. Unfortunately, nail
psoriasis is often difficult to treat.

Apremilast is an orally available small molecule inhibitor of phosphodiesterase 4 (PDE4) that
is FDA approved for the treatment of psoriasis and psoriatic arthritis. PDE4 is one of the
main phosphodiesterases expressed in immune cells, and its inhibition by apremilast is
thought to increase cyclic adenosine monophosphate and thereby decrease the inflammatory
response. Specifically, apremilast is believed to down regulate pro-inflammatory cytokines
including TNF-α, (Tumor necrosis Factor) IL-23 (Interleukin), IL-17, and others.

Apremilast has shown promising results for treating psoriatic arthritis and nail disease;
however more data is needed regarding its effect on nail psoriasis (Kavanaugh, et al). We
hypothesize that apremilast will prove to be highly effective in treating nail psoriasis. We
propose to conduct an open label clinical trial to investigate the efficacy and tolerability
of apremilast in treating nail psoriasis, where we will follow the package insert guidelines
for treating patients with apremilast.

Inclusion Criteria:

- - Patients older than 18

- Give written informed consent prior to any study procedures being conducted, and
candidates will authorize the release and use of protected health information (PHI)

- Be willing and consent to having photos taken of their fingernails

- Diagnosis of chronic plaque psoriasis that has been present for at least 6 months
prior to baseline

- Plaque psoriasis involving at least 5% of the patient's body surface area

- Nail psoriasis in at least one finger nail with a mNAPSI of 5 or greater

- A Nail Pain VAS score of 4 or higher. The Nail Pain VAS will assess the severity of
pain linked to the nail disease.

- Must have discontinued all systemic therapies for the treatment of psoriasis or
psoriatic arthritis at least 4 weeks or 5 half-lives, and biologics 2 months or 5
half-lives (whichever is longer) prior to baseline visit

- Must have discontinued all topical therapies for the treatment of psoriasis at least 2
weeks prior to baseline visit

- Subjects must have discontinued UV therapy at least 2 weeks prior to baseline and PUVA
(psoralen ultraviolet light therapy) at least 4 weeks prior to baseline.

- Subjects must be in good general health without significant uncontrolled
comorbidities, other than psoriasis, as determined by the investigator based on exam
findings, medical history, and clinical laboratories. Patients with stable mild renal
insufficiency are eligible for enrolling in this trial.

- Females of childbearing potential must use an approved birth control method while
receiving treatment and for 28 days following the last dose of apremilast, and there
must be a documented negative pregnancy tests prior to initiating treatment. Approved
birth control methods include hormonal contraception (oral, injection, implant,
transdermal patch, vaginal ring), intrauterine device, partners vasectomy, or male or
female condoms that are not made of natural materials plus a diaphragm with
spermicide, cervical cap with spermicide, or a contraceptive sponge with spermicide.
Females not of child bearing potential are defined as being at least 1 year
postmenopausal or surgically sterile (bilateral tubal ligation, bilateral oophorectomy
and/or hysterectomy).

- Male subjects, including those who have had a vasectomy, must use condoms not made of
natural materials for the duration of the trial and for at least 28 days after the
last dose of apremilast if conception is possible.

Exclusion Criteria:

- - Unable to comply with the protocol (as defined by the Investigator; i.e. drug or
alcohol abuse or history of noncompliance)

- Pregnancy or breastfeeding

- Female patients of childbearing potential and male patients who engage in activity
where contraception is possible who are unable to use the approved methods of
contraception throughout the length of the study and 28 days following the last dose

- Patients who have or have had thoughts of suicide or hurting themselves.

- Patients with prior exposure to apremilast

- Subject has been treated with an investigational drug within 30 days or 5 half-lives
(whichever is longer) prior to baseline visit.

- Patients with severe, progressive, or uncontrolled medical or psychiatric disease.

- Concomitant therapy with medications that are strong cytochrome P450 inducers,
including rifampin, phenobarbital, carbamazepine, or phenytoin

- Any other dermatologic conditions that prohibit or confound the ability of the
investigator to interpret skin and/or nail exam findings.

- Patients who will be unable to avoid the use of systemic steroids, excluding
intranasal or inhaled steroids that will be permitted, for the duration of the trial

- Any known hypersensitivity to apremilast

- Any subject who, in the opinion of the investigator, will be uncooperative or unable
to comply with duty procedures