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

A Phase 2B, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate-to-Severe Plaque-Type Psoriasis (Core Study)

The purpose of this study was to test if the drug apremilast was safe, if it helped improve psoriasis, and how well the participants tolerated it.

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