A Study to Evaluate the Impact of Apremilast on Magnetic Resonance Imaging (MRI) Outcomes in Adults With Psoriatic Arthritis
Condition: Psoriatic Arthritis
MeSH terms: Arthritis; Arthritis, Psoriatic
Intervention: Apremilast
Intervention description: Tablets for oral administration
Intervention MeSH terms: Apremilast
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 123.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Psoriatic Arthritis; CC-10004; MRI; apremilast

Summary:

      This study is designed to assess the efficacy of apremilast, either in monotherapy or with
      stable methotrexate, on imaging outcomes in adults with active psoriatic arthritis with less
      than 5 years of disease duration (since diagnosis), and who are naïve to biologic therapies.
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects must satisfy the following criteria to be enrolled in the study:

          1. Males or females, aged ≥ 18 years at time of consent

          2. For all regions, the local Regulatory Label for treatment with apremilast must be
             followed.

          3. Must understand and voluntarily sign an informed consent document prior to any study
             related assessments/procedures being conducted

          4. Able to adhere to the study visit schedule and other protocol requirements

          5. Have a documented diagnosis of PsA of ≥ 3 months AND ≤ 5 years in duration, meeting
             the Classification Criteria for Psoriatic Arthritis (CASPAR) at the time of Screening
             Visit

          6. Have ≥ 3 swollen AND ≥ 3 tender joints, with hand involvement (defined as ≥ 1 swollen
             joint or dactylitis [each clinically active joint of a dactylitic digit is counted as
             one joint]).

          7. Have at least 1 active enthesitis site (one of the Spondyloarthritis Research
             Consortium of Canada [SPARCC] or Leeds Enthesitis Index [LEI] sites)

          8. Must not have been treated previously with a tumor necrosis factor (TNF) blocker or
             other biologic drug for PsA treatment

          9. Must not have been treated with more than 2 conventional synthetic disease-modifying
             antirheumatic drugs (csDMARDs)

         10. Subjects taking csDMARDs, with the exception of methotrexate (MTX), cyclosporine, or
             leflunomide (LEF), do not require a washout period. However, they must discontinue the
             csDMARD treatment at least one day prior to their Baseline Visit (ie, Visit 2, Day 1)

         11. Subjects who have been previously treated with MTX for < 6 months and who are not on
             stable doses for at least 3 months will require a 28-day washout prior to the Baseline
             Visit to participate in the study

         12. Subjects who have been previously treated with LEF will require a 12-week washout
             prior to the Baseline Visit, or treatment with cholestyramine, per LEF prescribing
             label (ie, 8 g cholestyramine 3 times daily for 11 days)

         13. Subjects who have been previously treated with cyclosporine will require a 28-day
             washout prior to the Baseline Visit to participate in the study

         14. If taking MTX (≤ 25 mg/week), continuity of treatment will be allowed if duration of
             treatment is ≥ 6 months and on a stable dose for at least 3 months prior to the
             Baseline Visit

         15. If taking oral glucocorticoids, must be on a stable dose of prednisone ≤ 10 mg/day or
             equivalent for at least 4 weeks prior to the Baseline Visit

         16. If taking nonsteroidal anti-inflammatory drugs (NSAIDs) or narcotic analgesics, must
             be on stable dose for at least 4 weeks prior to Baseline Visit

         17. A female of childbearing potential (FCBP) must have a negative pregnancy test at
             screening and baseline. While on investigational product (IP) and for at least 28 days
             after taking the last dose of IP, a FCBP who engages 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
             (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device;
             tubal ligation; or partner's vasectomy; OR Option 2: Male or female condom (latex
             condom or non-latex 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.

         18. Must be in general good health (except for PsA) as judged by the investigator, based
             on medical history, physical examination, and clinical laboratories. (Note: The
             definition of good health means a subject does not have uncontrolled significant
             comorbid conditions).

        Exclusion Criteria:

        The presence of any of the following will exclude a subject from enrollment:

          1. Contraindication to MRI examination including, but not limited to, intracranial metal
             clips, heart pacemakers, insulin pumps, implanted hearing aids, neurostimulators,
             metal hip replacements, profound claustrophobia or inability to lie in the MRI machine
             in an appropriate position to obtain quality images, history of hypersensitivity to
             gadolinium contrast agent

          2. Severe renal impairment (creatinine clearance of less than 30 mL per minute estimated
             by the Cockroft-Gault equation), which would prevent the use of gadolinium enhancement

          3. History of clinically significant (as determined by the investigator) cardiac,
             endocrine, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic,
             immunologic disease, or other major uncontrolled disease

          4. Any condition, including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study

          5. Prior history of suicide attempt at any time in the subject's lifetime prior to
             signing the informed consent, or major psychiatric illness requiring hospitalization
             within the last 3 years prior to signing the informed consent.

          6. Pregnant or breast feeding

          7. Active substance abuse or a history of substance abuse within 6 months prior to
             screening

          8. History of allergy or hypersensitivity to any component of the IP

          9. History of rare hereditary problems of galactose intolerance, lapp lactase deficiency
             or glucose-galactose malabsorption

         10. History of positive human immunodeficiency virus (HIV), or congenital or acquired
             immunodeficiency (eg, Common Variable Immunodeficiency Disease)

         11. Active tuberculosis or a history of incompletely treated tuberculosis

         12. 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 and the infection cured, at least 4 weeks
             prior to screening and no new or recurrent infections prior to the Baseline Visit

         13. Malignancy or history of malignancy or myeloproliferative or lymphoproliferative
             disease within the past 3 years, except for treated (ie, cured) basal cell or squamous
             cell in situ skin carcinomas;

         14. Major surgery (including joint surgery) within 8 weeks prior to screening or planned
             major surgery within 6 months following Baseline Visit

         15. Rheumatic autoimmune disease other than PsA, including, but not limited to: systemic
             lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis, or
             fibromyalgia

         16. Prior history of or current inflammatory joint disease other than PsA (eg, gout,
             reactive arthritis, rheumatoid arthritis, ankylosing spondylitis, Lyme disease), which
             confounds the ability to interpret data from the study

         17. Prior treatment with any biologic DMARD

         18. Prior treatment with more than 2 csDMARDs

         19. Use of the following systemic therapy(ies) within 28 days of the Baseline Visit:
             cyclosporine or other calcineurin inhibitors, glucocorticoids exceeding 10 mg daily
             prednisone equivalent, as well as mycophenolate.

         20. Use of MTX within 4 weeks of the Baseline Visit, unless subject is on stable doses for
             at least 3 months and total treatment duration with MTX is ≥ 6 months

         21. Use of LEF within 12 weeks of the Baseline Visit, unless subject has taken
             cholestyramine, 8 g three times daily 11 days after stopping LEF

         22. Previous treatment with a Janus kinase (JAK) inhibitor (including tyrosine kinase 2
             [TYK2] inhibitor)

         23. Prior treatment with apremilast, or participation in a clinical study involving
             apremilast

         24. Use of intra-articular (IA) glucocorticoid injection within 8 weeks before the
             Baseline Visit.

         25. Use of any investigational drug within 4 weeks of the Baseline Visit, or 5
             pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer)