Apremilast as a Direct Treatment for Mild-to-moderate Plaque Psoriasis Versus Placebo: an Analysis of Clinical Safety and Efficacy

A Phase 3, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Mild to Moderate Plaque Psoriasis

This is a Phase 3, multicenter, randomized, placebo-controlled, double-blind study designed to evaluate the efficacy and safety of apremilast (CC-10004) in subjects with mild to moderate plaque psoriasis.

Approximately 574 subjects with mild to moderate plaque psoriasis will be randomized 1:1 to receive either apremilast 30 mg BID or placebo for the first 16 weeks.

The study will consist of four phases:

• Screening Phase - up to 35 days

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

  - Subjects will be randomly assigned to either apremilast 30 mg tablets orally BID or placebo tablets (identical in appearance to apremilast 30 mg tablets) orally BID.

• Apremilast Extension Phase - Weeks 16 to 32

  - All subjects will be switched to (or continue with) apremilast 30 mg BID. All subjects will maintain this dosing through Week 32.

• Observational Follow-up Phase - 4 weeks - Four-week Post-Treatment Observational Follow-up Phase for all subjects who complete the study or discontinue the study early.

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

1. Subject must be male or female, ≥18 years of age at the time of signing the informed consent form (ICF).
2. Subject must have a diagnosis of chronic plaque psoriasis for at least 6 months prior to signing the ICF.
3. Subject must have a diagnosis of mild to moderate plaque psoriasis at both Screening and Baseline.
4. Subject must be inadequately controlled with or intolerant of at least one topical therapy at both Screening and Baseline.
5. Subject must be in good health (except for psoriasis) as judged by the investigator, based on medical history, physical examination, clinical laboratories, and urinalysis.
6. Subject must meet laboratory criteria.
7. Subject has not had prior exposure to biologics for the treatment of psoriatic arthritis or psoriasis, or any other condition that could impact the assessment of psoriasis.

Exclusion Criteria:

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

1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
2. Subjects has 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.

2. Subject has hepatitis B surface antigen positive at Screening. 3. Subject has active tuberculosis (TB) or a history of incompletely treated TB.

4. Subject has history of positive human immunodeficiency virus (HIV), or has congenital or acquired immunodeficiency (eg, common variable immunodeficiency disease).

5. Subject has hepatitis B surface antigen or anti-hepatitis C antibody positive at Screening.

6. Subject has prior history of suicide attempt at any time in the subject's life time or major psychiatric illness requiring hospitalization within the last 3 years prior to signing the informed consent. 7. Subject has current or planned concurrent use of therapies that may have a possible effect on psoriasis during the course of the treatment phase of the trial.

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

9. Subject had prior treatment with apremilast.