A Study to Evaluate the Impact of Apremilast on Magnetic Resonance Imaging (MRI) Outcomes in Adults With Psoriatic Arthritis

A Phase 4, Multicenter, Single-Arm, Open-Label Study to Evaluate the Impact of Apremilast (CC-10004) on MRI Outcomes in Subjects With Active Psoriatic Arthritis

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.

This study consists of 3 phases:

• Screening Phase - up to 4 weeks

• Single-arm, Open-label Treatment Phase - Weeks 0 to 48

  • Participants will receive apremilast 30 mg BID (after a 5-day titration period) for the entire duration of this phase.
  • MRI of the most affected hand and whole body MRI (WB-MRI) will be performed at weeks 0, 24, and 48.
  • The hand with the greater inflammatory burden of swollen joints and/or dactylitis will be considered as the most affected hand. If both hands are equally affected, the dominant hand will be designated as the index hand.

• Observational Follow-up Phase - 4 Weeks

  • All participants who complete the study or discontinue early will participate in the 4-week Post-Treatment Observational Follow-up Phase.

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)