Efficacy and Safety Study of Apremilast (CC-10004) in Pediatric Subjects From 6 Through 17 Years of Age With Moderate to Severe Plaque Psoriasis

A PHASE 3, MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO ASSESS THE EFFICACY AND SAFETY OF APREMILAST (CC-10004) IN PEDIATRIC SUBJECTS FROM 6 THROUGH 17 YEARS WITH MODERATE TO SEVERE PLAQUE PSORIASIS

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

At least 230 pediatric subjects (ages 6 through 17 years) will be randomized 2:1 to receive either apremilast or placebo for the first 16 weeks and then all subjects will receive apremilast during the 36 week Extension Phase for a total of 52 weeks. Randomization to apremilast arm or placebo arm will be stratified by age group (6 to 11 years or 12 to 17 years). Subjects will receive apremilast treatment of either 20 mg twice daily (BID) or 30 mg BID, depending on weight. This Phase 3 study is being conducted to evaluate the safety and efficacy of apremilast in the treatment of pediatric subjects.

Treatment will be assigned by weight with subjects 20 kg to < 50 kg receiving apremilast 20 mg BID or placebo BID and subjects ≥ 50 kg receiving apremilast 30 mg BID or placebo BID. Total study duration is up to 71 weeks. Subjects completing all 52 weeks of the treatment and extension phase will be able to enter the Long-term study. Subjects not entering the Long-term study will return for 3 observational follow-up visits, 4, 8 and 14 weeks after last dose of study drug.

Inclusion Criteria:

1. Males or female subjects 6 to 17 years of age, inclusive, at the time the informed consent form is signed by the legal guardian

2. Subjects must have a weight of ≥ 20 kg

3. Diagnosis of chronic plaque psoriasis for at least 6 months prior to Screening.

4. Has moderate to severe plaque psoriasis at Screening and Baseline as defined by:

   • PASI score ≥ 12; and
   • Body surface area (BSA) ≥ 10%; and
   • sPGA ≥ 3 (moderate to severe)

5. Disease inadequately controlled by or inappropriate for topical therapy for psoriasis

6. Candidate for systemic therapy or phototherapy

Exclusion Criteria:

1. Guttate, erythrodermic, or pustular psoriasis at Screening and Baseline

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

3. Prior history of suicide attempt at any time in the subject's lifetime prior to Screening or randomization in the study, or major psychiatric illness requiring hospitalization within 3 years prior to signing the assent and informed consent

4. Answer "Yes" to any question on the Columbia-Suicide Severity Rating Scale during Screening or at Baseline

5. Current or planned concurrent use of the following therapies that may have a possible effect on psoriasis

   a. Topical therapy within 2 weeks prior to randomization (including but not limited to topical corticosteroids, topical retinoid or vitamin D analog preparations, tacrolimus, pimecrolimus, or anthralin/dithranol)

   Exceptions*:

   i. Low potency or weak corticosteroids (please refer to the Investigators' Manual) will be allowed as background therapy for treatment of the face, axillae and groin in accordance with manufacturer's suggested usage ii. Unmedicated skin moisturizer (eg, Eucerin®) will also be permitted for body lesions

   *Subjects should not use these topical treatments within 24 hours prior to the clinic visit.

   b. Conventional systemic therapy for psoriasis within 4 weeks prior to randomization c. Phototherapy treatment (ie, ultraviolet B [UVB], PUVA) within 4 weeks prior to randomization d. Biologic therapy within 4 weeks prior to randomization or 5 PK/PD half-lives (whichever is longer).