A Study to Evaluate the Impact of Apremilast (CC-10004) on MRI Outcomes in Subjects With Psoriatic Arthritis

Approximately 120 subjects will receive apremilast 30 mg BID, after a 5-day titration period,
with or without MTX. All subjects will be permitted to take NSAIDs and/or low-dose oral
glucocorticoids (prednisone ≤ 10 mg/day or equivalent) throughout the study. The NSAIDs and
low-dose oral glucocorticoids must be on a stable regimen for at least 4 weeks prior to
baseline. MTX (≤ 25 mg/week) will be permitted if treatment duration is ≥ 6 months and on a
stable regimen for at least 3 months prior to baseline. In addition, Nonsteroidal
anti-inflammatory drug (NSAIDs), and low-dose glucocorticoids must be continued from Day 1
through the Week 24 Visit. Change in doses, increase or decrease, and/or discontinuation will
not be allowed, except for safety reasons or for lack of availability. After the Week 24
Visit, the doses of MTX, NSAIDs, or glucocorticoids may be adjusted as clinically required.

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 CASPAR criteria for PsA 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 SPARCC or LEI sites)

10. Subjects taking csDMARDs, with the exception of MTX, cyclosporine, or 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 (ie, Visit 2, Day 1) 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 (ie, Visit 2, Day 1), 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 (ie, Visit 2, Day 1) 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 (ie,
Visit 2, Day 1) 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 (ie, Visit 2,
Day 1) 16. If taking NSAIDs or narcotic analgesics, must be on stable dose for at least 4
weeks prior to Baseline Visit (ie, Visit 2, Day 1) 17. A female of childbearing potential
(FCBP)† must have a negative pregnancy test at screening and baseline. While on 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.

† An FCBP is defined as a sexually mature female who 1) has not undergone a hysterectomy
(the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of
both ovaries) or 2) has not been postmenopausal for at least 24 consecutive months (that
is, has had menses at any time during the preceding 24 consecutive months).

§ The female subject's chosen form of contraception must be effective by the time the
female subject is screened into the study (for example, hormonal contraception should be
initiated at least 28 days before screening).

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

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 to any component of the IP

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. 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

12. 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;

13. Major surgery (including joint surgery) within 8 weeks prior to screening or planned
major surgery within 6 months following Baseline Visit

14. Rheumatic autoimmune disease other than PsA, including, but not limited to: systemic
lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis, or
fibromyalgia

15. Prior history of or current inflammatory joint disease other than PsA (eg, gout,
reactive arthritis, RA, ankylosing spondylitis, Lyme disease), which confounds the
ability to interpret data from the study

16. Prior treatment with any biologic DMARD

17. Prior treatment with more than 2 csDMARDs

18. Use of the following systemic therapy(ies) within 28 days of the Baseline Visit (ie,
Visit 2, Day 1): cyclosporine or other calcineurin inhibitors, glucocorticoids
exceeding 10 mg daily prednisone equivalent, as well as mycophenolate.

19. Use of MTX within 4 weeks of the Baseline Visit (ie, Visit 2, Day 1), unless subject
is on

20. Use of LEF within 12 weeks of the Baseline Visit (ie, Visit 2, Day 1), unless subject
has taken cholestyramine, 8 g three times daily 11 days after stopping LEF

21. Previous treatment with a JAK inhibitor

22. Prior treatment with apremilast, or participation in a clinical study involving
apremilast

23. Use of intra-articular (IA) glucocorticoid injection within 8 weeks before the
Baseline Visit (ie, Visit 2, Day 1).

24. Use of any investigational drug within 4 weeks of the Baseline Visit, or 5
pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer)