Phase 3b Safety and Efficacy Study of Apremilast to Treat Moderate to Severe Plaque-plaque Psoriasis

This is a phase 3b, multicenter, randomized, placebo-controlled, double-blind, double-dummy,
study of the efficacy and safety of apremilast, etanercept, and placebo, in subjects with
moderate to severe plaque psoriasis.

Approximately 240 subjects will be randomized 1:1:1 to the three treatment groups. All
subjects will receive both tablets and injections through Week 16.

The study will consist of four phases:

- Screening Phase - up to 35 days

- Double-blind Placebo-controlled Phase - Weeks 0-16

- Apremilast Extension Phase - Weeks 16-104

- Post-treatment Observational Follow-up Phase

During the double-blind, placebo-controlled phase, subjects will receive treatment with one
of the following:

- apremilast (APR) 30 mg tablets orally twice a day (BID) plus once weekly (QW)
evaluator/subject-blinded subcutaneous (SC) saline (placebo) injections (1 mL x 2
injections SC), or

- etanercept (ETN) 50 mg evaluator/subject-blinded subcutaneous (SC) once weekly (QW)
injections (2 x 25 mg) plus placebo tablets orally twice a day (BID), or

- placebo tablets and evaluator/subject-blinded subcutaneous (SC) saline (placebo)
injections.

All subjects will be asked to participate in a 4-week Post-treatment Observational Follow-up
Phase either upon completion of the study or upon discontinuation of investigational product
for those subjects who terminate the study early.

Inclusion Criteria:

- Males or females, ≥ 18 years of age

- Diagnosis of chronic, moderate to severe plaque psoriasis for at least 12 months
prior to Screening, and a candidate for phototherapy and/or systemic (including
etanercept) therapy

- Had an inadequate response, intolerance, or contraindication to at least 1
conventional systemic agent for the treatment of psoriasis.

- No prior exposure to biologics for treatment of psoriatic arthritis or psoriasis

Exclusion Criteria:

- Other than psoriasis, history of any clinically significant and uncontrolled systemic
diseases; 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.

- Pregnant or breast feeding.

- Have failed more than 3 systemic agents for treatment of psoriasis.

- History of allergy to any component of the investigational product (IP), including
human immunoglobulin (Ig) proteins or allergy to etanercept.

- Hepatitis B surface antigen or anti-hepatitis C antibody positive at Screening.

- Latent, active tuberculosis (TB) or inadequately treated TB; nontuberculous
mycobacterial infection or opportunistic infection (eg, cytomegalovirus, Pneumocystis
carinii, aspergillosis, Clostridium difficile).

- Have a history of, or ongoing, chronic or recurrent infectious disease

- Have received, or are expected to receive, any live virus or bacterial vaccination
within 3 months before first administration of IP, or through Week 20 during the
study.

- Had a Bacillus Calmette-Guérin (BCG) vaccination within 1 year prior to screening.

- History of positive human immunodeficiency virus (HIV), or have congenital or
acquired immunodeficiency (eg, common variable immunodeficiency disease).

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

- Malignancy or history of malignancy, except for treated [ie, cured] basal cell or
squamous cell in situ skin carcinomas and cervical intraepithelial neoplasia [CIN] or
carcinoma in situ of the cervix with no evidence of recurrence within the previous 5
years.

- Psoriasis flare or rebound within 4 weeks prior to Screening.

- Topical therapy within 2 weeks of randomization or systemic therapy for psoriasis
within 4 weeks prior to randomization

- Use of phototherapy within 4 weeks prior to randomization or prolonged sun exposure
or use of tanning booths or other ultraviolet (UV) light sources.

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

- Prior treatment with apremilast or etanercept.