A Study of Safety, Tolerability and Pharmacokinetics of Apremilast (CC-10004) in Pediatric Subjects With Moderate to Severe Plaque Psoriasis
Condition: Psoriasis
MeSH terms: Psoriasis
Intervention: Apremilast
Intervention MeSH terms: Apremilast
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 6 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Psoriasis; Moderate to Severe Plaque Psoriasis; Plaque Psoriasis; CC-10004; Apremilast; Pharmacokinetics; Open-label; Safety; Pediatric

Summary:

      This is a Phase 2, multicenter, open-label study in subjects with moderate to severe plaque
      psoriasis aged 6 to 17 years, inclusive, intended to assess the safety, tolerability, and PK
      of apremilast with 2 weeks of oral apremilast treatment followed by a 48-week extension of
      apremilast treatment. Moderate to severe plaque psoriasis is defined as Psoriasis Area
      Severity Index (PASI) ≥ 12, Body Surface Area (BSA) ≥ 10%, and static Physician Global
      Assessment (sPGA) of ≥ 3. The total study duration for each subject will last for up to a
      total of 107 weeks which includes screening, treatment (including the PK portion of the study
      and the extension treatment period), two short-term follow-up periods and a long-term
      follow-up period.
    

Eligibility criteria:

        Inclusion Criteria:

        - Subjects must satisfy all of the following criteria to be enrolled in the study:

          1. Male or female subjects 6 to 17 years of age, inclusive, at the time the informed
             consent document is signed by the legal guardian

          2. Group 1 Only: ages 12 to 17 years, inclusive, and weighs ≥ 35 kg

          3. Group 2 Only: ages 6 to 11 years, inclusive, and weighs ≥ 15 kg

          4. Subject is able to swallow the apremilast tablet

          5. Able to sign an assent with a legal guardian who can understand and voluntarily sign
             an informed consent

          6. Able to adhere to the study visit schedule and other protocol requirements

          7. Must agree to withhold vaccinations during the first 2 weeks of dosing. Inactivated
             vaccines will be allowed during the extension treatment period

          8. Diagnosis of chronic plaque psoriasis for at least 6 months prior to Screening

          9. Have moderate to severe plaque psoriasis at Screening and Baseline as defined by:

               -  Psoriasis Area and Severity Index (PASI) score ≥ 12; and

               -  Body surface area (BSA) ≥ 10%; and

               -  Static Physician Global Assessment (sPGA) ≥ 3 (moderate to severe)

         10. Disease inadequately controlled by or inappropriate for topical therapy for psoriasis

         11. Candidate for systemic or phototherapy

         12. Have not been exposed to any or have been exposed to no more than one systemic agent
             for psoriasis

         13. At Screening, laboratory values must be within the following ranges:

               -  White blood cell (WBC) count Age (yrs) Males (x 103 /µL) Females (x 103 /µL) 6-11
                  3.5 - 13.65 3.5 - 13.65 12-18 3.5 - 13.15 3.5 - 13.15

               -  Platelet count Age (yrs) Males (x 103 /µL) Females (x 103 /µL) 6-11 117 - 394 117
                  - 394 12-18 126 - 400 126 - 400

               -  Hemoglobin (Hb) Age (yrs) Males (g/dL) Females (g/dL) 6-11 10.0 - 15.5 10.0 -
                  15.5 12-18 11.0 - 18.1 10.0 - 16.4

         14. Male subjects who engage in activity in which conception is possible must use barrier
             contraception (male latex condom or nonlatex condom NOT made out of natural [animal]
             membrane [for example, polyurethane]) while on apremilast and for at least 28 days
             after the last dose of apremilast

         15. 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 for at least 28 days after dministration of the last
             dose of apremilast. For the purposes 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 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 * Periodic abstinence (eg, calendar, ovulation, symptothermal,
             post-ovulation methods) and withdrawal are not acceptable methods of contraception.

        Exclusion Criteria:

          -  The presence of any of the following will exclude a subject from enrollment:

               1. History of or currently active inflammatory bowel disease

               2. Major concurrent medical conditions, pregnancy or lactation

               3. Any condition that confounds the ability to interpret data from the study

               4. Guttate, erythrodermic, or pustular psoriasis

               5. Psoriasis flare or rebound within 4 weeks prior to Screening

               6. Evidence of skin conditions that would interfere with clinical assessments

               7. History of human immunodeficiency virus infection, or positive result to
                  hepatitis B surface antigen or hepatitis C antibodies at Screening

               8. Clinically significant abnormality on 12-Lead ECG at Screening

               9. History of active mycobacterial infection with any species (including
                  Mycobacterium tuberculosis) within 3 years of the Screening Visit and without
                  documentation of successful treatment

              10. Congenital and acquired immunodeficiencies (eg, Common Variable
                  Immunodeficiency),immunoglobulin A deficiency

              11. History of recurrent significant infections

              12. Active infection or infection treated with antibiotic treatment within 2 weeks of
                  first dose

              13. Any history of or active malignancy

              14. History of allergy/intolerance to any component of the investigational product,
                  ie, apremilast, lactose monohydrate, microcrystalline cellulose, croscarmellose
                  sodium, magnesium stearate, hypromellose 15 cP, titanium dioxide, polydextrose
                  FCC, talc, maltodextrin, medium chain triglycerides, iron oxide red, iron oxide
                  yellow, and iron oxide black.

              15. Deficiencies in lactose metabolism, ie, galactose-1-phosphate
                  uridylyltransferase, UDPglactose 4-epimerase, galactokinase or Fanconi Bickel
                  syndrome, including congenital lactase deficiencies, and glucose-galactose
                  malabsorption.

              16. Any other significant medical condition, laboratory abnormality, or psychiatric
                  illness that would prevent the subject from participating in the study or which
                  places the subject at unacceptable risk if he/she were to participate in the
                  study

              17. Prior history of suicide attempt at any time in the subject's lifetime prior to
                  screening or enrollment in the study or major psychiatric illness requiring
                  hospitalization within 3 years

              18. Answering '"Yes'" to any question on the Columbia-Suicide Severity Rating Scale
                  during screening or at baseline

              19. Having received biologic therapy within 5 terminal half-lives, including but not
                  limited to the following time periods:

                    -  Four weeks prior to baseline for etanercept

                    -  Ten weeks prior to baseline for adalimumab

                    -  Twenty-four weeks prior to baseline for ustekinumab

              20. Topical therapy within 2 weeks of baseline (including but not limited to topical
                  corticosteroids, topical retinoid or vitamin D analog preparations, tacrolimus,
                  pimecrolimus, or anthralin/dithranol)

                    -  Exceptions: low-potency corticosteroids (please refer to the Investigators'
                       Manual) will be allowed as background therapy for treatment of the face,
                       axillae, and groin in accordance with the manufacturers' suggested usage
                       during the course of the study

                    -  Subjects with scalp psoriasis will be permitted to use coal tar shampoo
                       and/or salicylic acid scalp preparations on scalp lesions

                    -  An unmedicated skin moisturizer (eg, Eucerin®) will be also permitted for
                       body lesions only. Subjects should not use these topical treatments within
                       24 hours prior to the clinic visit

              21. Systemic therapy for psoriasis within 4 weeks prior to baseline (including but
                  not limited to cyclosporine, corticosteroids, methotrexate, oral retinoids,
                  mycophenolate, thioguanine, hydroxyurea, sirolimus, sulfasalazine, azathioprine,
                  and fumaric acid esters)

              22. Use of phototherapy (ie, UVB, PUVA)within 4 weeks prior to baseline

              23. Use of any investigational drug within 4 weeks prior to baseline, or 5
                  pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer)

              24. 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

              25. Prior treatment with apremilast