A Study of the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Moderate to Severe Plaque Psoriasis of the Scalp

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

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

Approximately 300 subjects with moderate to severe plaque psoriasis of the scalp will be randomized 2:1 to receive either apremilast 30 mg twice daily (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 receive treatment with one of the following:

  • 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 who had received placebo during the placebo-controlled phase will be switched to apremilast 30 mg BID (or continue with) apremilast. At Week 16, all subjects will maintain this dosing through Week 32.

• Observational Follow-up Phase

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

Inclusion Criteria:

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

• Males or females, ≥ 18 years of age at the time of signing the informed consent document
• Be willing and able to adhere to the study visit schedule and other protocol requirements.
• Have a diagnosis of moderate to severe plaque psoriasis of the scalp at screening and baseline
• Must be a candidate for phototherapy and/or systemic therapy for either body or scalp psoriasis lesions.
• Have moderate to severe plaque psoriasis at screening and baseline
• Must be in good health (except for psoriasis) as judged by the Investigator, based on medical history, physical examination, 12-lead electrocardiogram (ECG), clinical laboratories, and urinalysis
• Must meet laboratory criteria
• Females of childbearing potential (FCBP)* must have a negative pregnancy test at screening and baseline. While on investigational product (IP) 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:

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

• Other than psoriasis, history of any clinically significant uncontrolled disease.

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
• Hepatitis B surface antigen positive at screening
• Anti-hepatitis C antibody positive at screening
• Active tuberculosis (TB) or a history of incompletely treated TB
• Clinically significant abnormality on 12-lead electrocardiogram (ECG) at 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 signing the informed consent form.
• Bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of signing the informed consent form.
• Malignancy or history of malignancy, except for treated (i.e., cured) basal cell or squamous cell in situ skin carcinomas or treated (i.e., cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix with no evidence of recurrence within 5 years of signing the informed consent.
• Prior history of suicide attempt at any time in the subject's life time prior to signing the informed consent and randomization, or major psychiatric illness requiring hospitalization within the last 3 years prior to signing the informed consent.
• Psoriasis flare/rebound within 4 weeks of signing the informed consent form or between the screening and baseline visits.
• Topical therapy within 2 weeks prior to randomization; Conventional systemic therapy for psoriasis within 4 weeks prior to randomization; Intralesional corticosteroids on the scalp within 2 weeks prior to randomization; Phototherapy treatment of body or scalp psoriasi lesions within 4 weeks prior to randomization; Biologic therapy between 12 weeks to 24 weeks prior to randomization
• Use of any investigational drug beginning 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer)
• Prolonged sun exposure or use of tanning booths or other ultraviolet (UV) light sources
• Prior treatment with apremilast
• History of allergy or hypersensitivity to any components of the Investigational product.