Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate-to-Severe Plaque-Type Psoriasis (Core Study)

This study fully explored the extent of treatment benefit achieved with doses of apremilast
up to 30 mg by mouth (PO) twice daily (BID) with treatment duration for up to 6 months. In
addition, it was important to determine the minimally effective dose for apremilast and more
fully elucidate the dose response curve in this patient population. The results from this
study helped guide the selection of the dose in the phase 3 trials.

Participants meeting eligibility criteria at the Baseline Visit (Week 0) were centrally
randomized with the use of a permuted-block randomization list, with equal allocation to
each of the four treatment arms: 10 mg, 20 mg or 30 mg PO BID of apremilast or placebo. In
an effort to mitigate the dose-dependent adverse effects of apremilast (e.g., headache or
gastrointestinal disturbances), participants had their dose titrated over a 7-day period
(Days 1 through7). Participants received 10 mg PO BID of apremilast or identically-appearing
placebo during Days 1 to 2. Participants randomized to the 10 mg BID dose continued taking
this dose throughout the treatment phase of the study. Those participants randomized to the
20 mg BID dose were dose titrated to 20 mg PO BID of apremilast or identically-appearing
placebo during Days 3 to 4 of dosing. Participants randomized to the 20 mg BID dose
continued taking this dose throughout the treatment phase of the study. Those participants
randomized to the 30 mg BID dose were dose titrated to 30 mg PO BID of apremilast or
identically-appearing placebo during Days 5 to 7 and continued taking this dose throughout
the treatment phase of the study. At Week 16, all participants originally randomized to the
placebo arm were re-randomized to 20 mg BID or 30 mg BID of apremilast. All participants
(i.e., those that were continuing their Apremilast dosing regimen, as well as those that
were switched from placebo to apremilast) received drug at Week 16 in a treatment arm in a
blinded fashion. In addition, participants who transitioned from placebo to active
medication at Week 16 completed a dose titration schedule to help mitigate any potential GI
side effects that may have jeopardized the blinding of the treatment arms.

At Week 24 (end of core study and beginning of an extension study), participants were given
the option to enroll into an extension study (PSOR-005E NCT00953875) and continue on the
same apremilast dosage they had received at the end of the core study, during Weeks 24-52, a
total of 28 weeks. Participants who elected not to enter into the treatment extension study,
completed a 4-week observational follow-up phase of the core study. At Week 52 (end of
extension study and beginning of a long-term extension study), participants were given the
option to enroll into a long term extension study (PSOR-005LTE NCT01130116), for 4
additional years. Participants who were treated with apremilast 10 mg BID in the extension
study were randomly assigned and dose titrated to either apremilast 20 mg BID or 30 mg BID.
Participants who were dosed with 20mg or 30 mg BID in the extension study continued to
receive the same dose in the long-term extension study. The long-term extension study is
anticipated to complete in May 2016.

Inclusion Criteria:

- Understand and voluntarily sign an informed consent form

- ≥18 years of age at the time of signing the informed consent form

- Able to adhere to the study visit schedule and other protocol requirements.

- Diagnosis of chronic, stable plaque psoriasis at least 6 months prior to screening as
defined by:

1. PASI (Psoriasis Area and Severity Index) score ≥ 12

2. Body Surface Area (BSA) ≥ 10%

- Candidate for photo/systemic therapy

- In good health as judged by the investigator, based on medical history, physical
examination, 12-lead electrocardiogram (ECG), serum chemistry, hematology,
immunology, and urinalysis

- Meet all laboratory criteria as defined per protocol

- Females of childbearing potential (FCBP) must have a negative urine pregnancy test at
screening (Visit 1). In addition, sexually active FCBP must agree to use TWO of the
following adequate forms of contraception methods. A FCBP must agree to have
pregnancy tests every 4 weeks while on study medication

- Males (including those who have had a vasectomy) must agree to use barrier
contraception (latex condoms) when engaging in reproductive sexual activity with FCBP
while on study medication and for 84 days after taking the last dose of study
medication

Exclusion Criteria:

- History of clinically significant disease (as determined by the investigator)

- Pregnant or breastfeeding

- History of active mycobacterial infection within 3 years

- History of Human Immunodeficiency Virus (HIV) infection

- Congenital and acquired immunodeficiencies

- Hepatitis B surface antigen positive or Hepatitis B core antibody positive at
screening

- Antibodies to Hepatitis C at screening

- Malignancy or history of malignancy except for treated [i.e., cured] basal-cell skin
carcinomas

- Any condition, including the presence of laboratory abnormalities, that places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study

- Psoriasis flare within 4 weeks of screening

- Topical therapy within 2 weeks of randomization

- Systemic therapy for psoriasis within 4 weeks of randomization

- Use of phototherapy within 4 weeks of randomization [(i.e., Ultraviolet (UVB),
Psoralens and long-wave ultraviolet radiation (PUVA)]

- Adalimumab, etanercept, efalizumab or infliximab within 12 weeks of randomization

- Alefacept within 24 weeks of randomization

- Investigational drug within 4 weeks of randomization, or 5
pharmacokinetic/pharmacodynamic half lives, if known (whichever is longer)

- Prolonged sun exposure or use of tanning booths or other ultraviolet light sources