Ensayos clínicos

Inclusion Criteria:

• Males or female subjects 6 to 17 years of age, inclusive, at the time the informed consent form is signed by the legal guardian.
• Subjects must have a weight of ≥ 20 kg.
• Subjects must have an age and sex specific BMI value no lower in range than the 5th percentile on the Centers for Disease Control (CDC) growth chart for children and adolescents (CDC, 2000).
• Subject is able to swallow the study medication tablet.
• Able to sign an age-appropriate assent with a legal guardian(s) who understand(s) and voluntarily sign(s) an informed consent prior to any study-related assessments/procedures being conducted.
• Be willing and able to adhere to the study visit schedule and other protocol requirements.
• Diagnosis of chronic plaque psoriasis for at least 6 months prior to Screening.
• 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).
• Disease inadequately controlled by or inappropriate for topical therapy for psoriasis.
• Candidate for systemic therapy or phototherapy.
• At Screening, laboratory values must be within the following ranges:
  • White blood cell (WBC) count
  • Age (years) | Males (x 10^3 /μL) | Females (x 10^3 /μL)
    • 6-11 | 3.5 – 13.5 | 3.5 – 13.5
    • 12-18 | 3.5 – 13.5 | 3.5 – 13.5
  • Platelet count
  • Age (years) | Males (x 10^3 /μL) | Females (x 10^3 /μL)
    • 6-11 | 125 – 400 | 125 – 400
    • 12-18 | 125 – 400 | 125 – 400
  • Serum creatinine ≤ 1.2 x upper-limit of normal (ULN) for age and gender.
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 1.5 x ULN for age and gender. If initial test of ALT or AST is > 1.5 x ULN, one repeat test is allowed during Screening. Please see the reference ranges of the central laboratory.
  • Total bilirubin ≤ 2 mg/dL (≤ 34 μmol/L). If initial test result is > 2 mg/dL, one repeat test is allowed during the Screening period 
  • Hemoglobin (Hb)
  • Age (years) | Males (g/dL) | Females (g/dL)
    • 6-11 | 10.0 – 15.0 | 10.0 – 15.0
    • 12-18 | 11.0 – 16.5 | 10.5 – 15.5
• All females of childbearing potential (FCBP) must either practice abstinence* from heterosexual contact or use one of the approved contraceptive options as described below while on apremilast and during any dose interruption, and for at least 28 days after administration of the last dose of apremilast. For the purpose of this study, a female subject is considered of childbearing potential if she is ≥ 12 years old or has reached menarche, whichever occurred first.
• At the time of study entry, and at any time during the study when a female subject of childbearing potential’s contraceptive measures or ability to become pregnant changes, the Investigator will educate the subject regarding abstinence or contraception options and the correct and consistent use of effective contraceptive methods in order to successfully prevent pregnancy.
• Females of childbearing potential must have a negative pregnancy test at Screening and Baseline. All 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 (for example, birth control pills, intravaginal ring, transdermal patch, injection, implant); intrauterine device (IUD); tubal ligation; or partner’s vasectomy; OR
  • Option 2: Male or female latex condom or nonlatex condom NOT made out of natural (animal) membrane (for example,  polyurethane); PLUS one additional barrier method:
    • diaphragm with spermicide;
    • cervical cap with spermicide; or
    • contraceptive sponge with spermicide

  • NOTE: Option 2 may not be acceptable as a highly effective contraception option in all countries per local guidelines/regulations.

• * True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• + If a female subject is a FCBP when entering the study, the 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:

• Other than psoriasis, history of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major uncontrolled disease.
• Any condition, including the presence of laboratory abnormalities, or psychiatric illness, that would place the subject at unacceptable risk if he/she were to participate in the study.
• Any condition that confounds the ability to interpret data from the study.
• Evidence of skin conditions, other than psoriasis, that would interfere with clinical assessments.
• Pregnant or breastfeeding.
• Guttate, erythrodermic, or pustular psoriasis at Screening and Baseline.
• Psoriasis flare or rebound within 4 weeks prior to Screening.
• Positive Hepatitis B surface antigen, or anti-hepatitis C antibody, at Screening.
• History of positive human immunodeficiency virus infection (HIV), congenital and acquired immunodeficiencies (eg, common variable immunodeficiency, immunoglobulin A deficiency).
• Active tuberculosis (TB) or a history of incompletely treated TB.
• History of recurrent significant infections.
• Active infection or infection treated with antibiotic treatment within 2 weeks of first dose.
• Any history of or active malignancy.
• History of allergy/intolerance to any component of the investigational product; i.e., apremilast, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, hypromellose 15cP, titanium dioxide, polydextrose food chemical color, talc, maltodextrin, medium chain triglycerides, iron oxide red, iron oxide yellow, and iron oxide black.
• Deficiencies in lactose metabolism, ie, galactose-1-phosphate uridylyltransferase, UDPgalactose 4-epimerase, galactokinase or Fanconi Bickel syndrome, including congenital lactase deficiencies, and glucose-galactose malabsorption.
• 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.
• Answer “Yes” to any question on the Columbia-Suicide Severity Rating Scale during Screening or at Baseline.
• Current or planned concurrent use of the following therapies that may have a possible effect on psoriasis. 
  • 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*:
      • 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;
      • 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.
  • Conventional systemic therapy for psoriasis within 4 weeks prior to randomization (including but not limited to cyclosporine, corticosteroids, methotrexate, oral retinoids, mycophenolate, thioguanine, hydroxyurea,  sirolimus, sulfasalazine, azathioprine, and fumaric acid esters).
  • Phototherapy treatment (ie, ultraviolet B [UVB], PUVA) within 4 weeks prior to randomization.
  • Biologic therapy:
    • Etanercept (or biosimilar) treatment four weeks prior to randomization;
    • Adalimumab (or biosimilar) treatment ten weeks prior to randomization;
    • Other TNF or IL-17 blockers (such as infliximab, certolizumab pegol, secukinumab, ixekizumab, brodalumab, or their biosimilars) within 12 weeks prior to randomization;
    • Anti-IL-12 or anti-IL-23 treatment (such as ustekinumab, guselkumab, or tildrakizumab) within 24 weeks prior to randomization.
  • Use of any investigational drug within 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.
• Children in Care: a child who has been placed under the control or protection of an agency, organization, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation.
• Prior treatment with apremilast.