Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis (PsA)
Condition: Psoriatic Arthritis
MeSH terms: Arthritis; Arthritis, Psoriatic
Intervention: Apremilast 20mg; Apremilast 30mg; Placebo
Intervention description: Apremilast 20mg twice daily, orally; Apremilast 30mg twice daily, orally; Placebo
Intervention MeSH terms: Thalidomide; Apremilast
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 529.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: psoriasis; Arthritis; Psoriatic Arthritis; inflammation; skin condition; inflammatory cells; apremilast; CC-10004; phosphodiesterase type 4

Summary:

      The purpose of this study is to determine whether apremilast is safe and effective in the
      treatment of patients with psoriatic arthritis who have not been previously treated with
      DMARDs.

      Apremilast is proposed to improve signs and symptoms of psoriatic arthritis (tender and
      swollen joints, pain, physical function) in treated patients.
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects must satisfy the following criteria to be enrolled in the study:

          1. Male or female, aged ≥ 18 years at time of consent.

          2. Must understand and voluntarily sign an informed consent document prior to any study
             related assessments/procedures being conducted.

          3. Able to adhere to the study visit schedule and other protocol requirements.

          4. Have a documented diagnosis of Psoriatic Arthritis (PsA, by any criteria) of ≥ 3
             months duration.

          5. Meet the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria for PsA at
             time of screening.

          6. Have ≥ 3 swollen AND ≥ 3 tender joints.

          7. Have not been previously treated with disease-modifying antirheumatic drugs (DMARDS)
             (small molecules or biologics)

          8. Be receiving treatment on an outpatient basis.

          9. If taking oral corticosteroids, must be on a stable dose of prednisone ≤ 10 mg/day or
             equivalent for at least 1 month prior to screening.

         10. If taking nonsteroidal anti-inflammatory drugs (NSAIDs) or narcotic analgesics, must
             be on stable dose for at least 2 weeks prior to screening and until they have
             completed the Week 24 study visit.

         11. Low potency topical corticosteroids (Appendix M or locally available equivalent) will
             be allowed as background therapy for treatment of psoriasis on 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. A non-medicated skin emollient
             (eg, Eucerin cream) will also be permitted for body lesions only. Subjects must not
             use these treatments within 24 hours prior to the clinic visit.

         12. Meet the following laboratory criteria:

               -  White blood cell count ≥ 3000/mm3 (≥ 3.0 x 109/L) and < 14,000/mm3 (< 14 x 109/L)

               -  Platelet count ≥ 100,000/mm3 (≥ 100 x 109/L)

               -  Serum creatinine ≤ 1.5 mg/dL(≤ 132.6 μmol/L)

               -  Aspartate aminotransferase/Serum glutamic oxaloacetic transaminase (AST/SGOT) and
                  Alanine aminotransferase/Serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 2 x
                  upper limit of normal (ULN)

               -  Total bilirubin ≤ 2 mg/dL (≤ 34 μmol/L)

               -  Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L)

               -  Hemoglobin A1c ≤ 9.0%

         13. Male subjects (including those who have had a vasectomy) who engage in activity in
             which conception is possible must use barrier contraception (latex condom or any
             nonlatex condom NOT made out of natural [animal] membrane [eg, polyurethane]) while on
             IP and for at least 28 days after the last dose of IP.

         14. Females of childbearing potential (FCBP) must have a negative pregnancy test at
             Screening and Baseline. FCBP who engage in activity in which conception is possible
             must use 2 forms of contraception while on investigational product (IP) and for at
             least 28 days after the last dose of IP: one highly effective form (ie, hormonal,
             intrauterine device [IUD], tubal ligation, vasectomized partner) and one additional
             form (latex condom or any nonlatex condom NOT made out of natural [animal] membrane
             [eg, polyurethane], diaphragm, sponge). If one highly effective form of contraception
             cannot be used, then 2 forms of barrier contraception must be used, ie, latex condom
             or any nonlatex condom NOT made out of natural (animal) membrane (eg, polyurethane)
             with either of the following: sponge with spermicide or diaphragm with spermicide.

        Exclusion Criteria:

          1. History of clinically significant (as determined by the Investigator) cardiac,
             endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic,
             immunologic disease, or other major uncontrolled disease.

          2. 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.

          3. Clinically significant abnormality on 12-lead electrocardiography (ECG) at Screening.

          4. Pregnant or breast feeding.

          5. History of allergy to any component of the IP.

          6. Hepatitis B surface antigen positive at screening.

          7. Hepatitis C antibody positive at screening.

          8. AST/SGOT and/or ALT/SGPT > 1.5 x ULN and total bilirubin > ULN or albumin < lower
             limit of normal (LLN).

          9. History of positive Human Immunodeficiency Virus (HIV), or congenital or acquired
             immunodeficiency (eg, Common Variable Immunodeficiency Disease).

         10. Active tuberculosis or a history of incompletely treated tuberculosis.

         11. Clinically significant abnormality based upon chest radiograph with at least PA view
             (radiograph must be taken within 12 weeks prior to Screening or during the Screening
             visit). An additional lateral view is strongly recommended but not required.

         12. Active substance abuse or a history of substance abuse within 6 months prior to
             Screening.

         13. Bacterial infections requiring treatment with oral or injectable antibiotics, or
             significant viral or fungal infections, within 4 weeks of Screening. Any treatment for
             such infections must have been completed at least 4 weeks prior to Screening.

         14. Malignancy or history of malignancy (except for treated [ie, cured] basal cell or
             squamous cell in situ skin carcinomas and treated [ie, cured] cervical intraepithelial
             neoplasia [CIN] or carcinoma in situ of the cervix).

         15. Major surgery (including joint surgery) within 8 weeks prior to screening or planned
             major surgery within 6 months following randomization.

         16. Erythrodermic, guttate, or pustular psoriasis.

         17. Topical therapy for psoriasis, except as noted in the Inclusion Criteria, within 2
             weeks of randomization (including but not limited to topical corticosteroids, topical
             retinoids or vitamin D analog preparations, tacrolimus, pimecrolimus, or anthralin).

         18. Rheumatic autoimmune disease other than PsA, including systemic lupus erythematosis
             (SLE), mixed connective tissue disease (MCTD), scleroderma, or polymyositis.

         19. Functional Class IV as defined by the ACR Classification of Functional Status in
             Rheumatoid Arthritis (Appendix Q).

         20. Prior history of or current inflammatory joint disease other than PsA (eg, gout,
             reactive arthritis, RA, ankylosing spondylitis, Lyme disease).

         21. Prior use of disease modifying antirheumatic drugs (DMARDS; small molecules or
             biologics).

         22. Use of the following systemic therapy(ies) within 4 weeks of randomization, including
             but not limited to corticosteroids (except as noted in inclusion criteria), oral
             retinoids and fumaric acid esters.

         23. Use of phototherapy within 4 weeks of randomization (ie, UVB, PUVA).

         24. Previous treatment with any cell depleting therapies, including investigational agents
             (eg, rituximab, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, and anti-CD20).

         25. Treatment with intravenous gamma globulin, plasmapheresis, or Prosorba® column within
             6 months of baseline.

         26. Any previous treatment with alkylating agents such as cyclophosphamide or
             chlorambucil, or with total lymphoid irradiation.

         27. Prior treatment with apremilast.

         28. Use of any investigational drug within 4 weeks of randomization, or 5 pharmacokinetic/
             pharmacodynamic half lives, if known (whichever is longer).