A Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Early, Oligoarticular Psoriatic Arthritis Despite Initial Stable Treatment With Either NSAIDS and/or ≤ 1 Conventional Synthetic DMARD
Phase: PHASE4
Conditions: Arthritis, Psoriatic
Sponsor: Amgen

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TITLE PAGE 
A PHASE 4, MULTICENTER, RANDOMIZED, 
DOUBLE-BLIND, PLACEBO-CONTROLLED, 
PARALLEL-GROUP STUDY TO EVALUATE THE 
EFFICACY AND SAFETY OF APREMILAST (CC-10004) 
IN SUBJECTS WITH EARLY, OLIGOARTICULAR 
PSORIATIC ARTHRITIS DESPITE INITIAL STABLE 
TREATMENT WITH EITHER NSAIDS AND/OR  1 
CONVENTIONAL SYNTHETIC DMARD 
 
PROTOCOL NUMBER: 
 
CC-10004-PSA-013 
DATE FINAL: 
 
09 JUL 2018  
AMENDMENT 1 DATE FINAL: 
 
05 FEB 2019 
AMENDMENT 2 DATE FINAL: 
 
17 MAY 2019 
AMENDMENT 3 DATE FINAL 
 
04 MAY 2020 
AMENDMENT 4 DATE FINAL 
 
03 FEB 2021 
AMENDMENT 5 DATE FINAL 
 
12 JUL 2021 
EudraCT NUMBER: 
 
2018-002735-26 
IND NUMBER: 
 
101761 
NCT NUMBER 
 
NCT03747939 
SPONSOR NAME/ ADDRESS: 
 
Amgen Inc, 
Amgen Center Dr, Thousand Oaks, 
CA 91320 
USA  
 
Confidentiality Notice 
This document contains confidential information of Amgen. This document must not 
be disclosed to anyone other than the site study staff and members of the institutional 
review board/independent ethics committee/institutional scientific review board or 
equivalent. The information in this document cannot be used for any purpose other 
than the evaluation or conduct of the clinical investigation without the prior written 
consent of Amgen. If you have questions regarding how this document may be used 
or shared, call the Amgen Medical Information number: 1- 800-77-AMGEN 

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MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION  
Contact Information 
Global 
 
Name: 
, MD 
Title: 
Medical Director Global Development 
Amgen Inc. 
Address:  
Amgen Inc, 
Amgen Center Dr, Thousand Oaks, CA 91320 
USA 
Phone: 
E-mail: 
Note: Only call Amgen Medical Information, if you are not able to reach the Clinical 
Research Physician(s) or Medical Monitor or designee for emergency calls.  
 
Amgen Medical Information:  1- 800-77-AMGEN (1 800-772-6436)  
 
 
 
SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
 
 
 
 
Signature of Site Principal Investigator 
 
dd mmm yyyy 
 
 
Printed Name of Site Principal Investigator 
Institution Name:____________________________________ 

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By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Amgen representatives, the Declaration of Helsinki, International Council for 
Harmonisation (ICH), Good Clinical Practices Guidelines, and local regulations 
governing the conduct of clinical studies. 
 
 

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PROTOCOL SUMMARY 
Study Title 
A phase 4, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to 
evaluate the efficacy and safety of apremilast (CC-10004) in subjects with early, oligoarticular 
psoriatic arthritis despite initial stable treatment with either non-steroidal anti-inflammatory 
drugs (NSAIDs) and/or 1 conventional synthetic disease-modifying antirheumatic 
drugs (DMARD). 
Indication 
Psoriatic arthritis (PsA) is a heterogeneous inflammatory rheumatologic disorder characterized 
by inflammatory arthritis affecting 6 to 39 of patients suffering from psoriasis. PsA is 
classified as a seronegative spondyloarthropathy (SpA) because it shares certain features with 
other conditions included in that group. Indeed, spinal involvement has been reported in up to 
50 of patients with PsA. In addition, PsA is associated with enthesitis and dactylitis, which are 
common to SpA. Finally, the majority of patients with PsA are negative for rheumatoid factor 
(RF) (Gladman, 2005; Kruithof, 2005; Roberts, 1976). 
Asymmetrical oligoarthritis sometimes involving distal interphalangeal (DIP) joints, is a frequent 
form of PsA (Ritchlin, 2017). Despite this, very little is known with respect to the burden of 
disease and the appropriate management of patients with asymmetrical oligoarthritis. Indeed, 
there is a paucity of data on the treatment of patients with oligoarthritis since published clinical 
trials focus on polyarticular forms of the disease. Likewise, treatment recommendations tend to 
also focus on polyarticular forms (Gossec, 2016). Knowledge regarding the efficacy of drugs in 
oligoarticular forms would be of great value to clinicians. 
Standard classification criteria of ‘oligoarticular PsA’ for use in clinical studies remain to be 
established. In recent studies, patients with  4 active joint counts (tender and/or swollen) at 
baseline were classified as oligoarticular (Coates, 2013; Helliwell, 2007; Jones, 1994; Kane, 
2003). Using this definition, the proportion of subjects with oligoarthritis appears to range from 
14 to 63, the higher values being observed in patients with shorter disease duration. It is 
believed that the evolution of the disease, from oligoarthritis to polyarthritis, accounts for the 
lower proportion of patients with oligoarthritis in populations with longer disease duration. 
Indeed, results from the long-term follow-up of PsA cohorts, including subjects with short 
articular symptoms duration ( 24 months), showed that about two third of subjects presenting 
with an oligoarthritic disease at baseline evolved into the polyarticular sub-type over time 
(Jones, 1994). In addition, treatments with conventional synthetic DMARDs (csDMARDs) were 
associated with the reclassification of subjects, from polyarthritic at the initial clinical 
presentation into oligoarthritic at follow-up (Kane, 2003). Such oligoarticular patients may be 
associated with residual joints that are less responsive to treatment when compared to patients 
with recent onset of oligoarthritis. Taken together, these observations suggest that patients with 
oligoarticular form of PsA but with long standing disease duration and previous response to 
anti-rheumatic treatments may be less sensitive to further improvement after additional therapies 
than earlier populations who are mainly csDMARDs-naive. Therefore, the current study will 
enroll subjects with short disease duration and limited exposure to prior NSAIDs and/or 
csDMARDs. 

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Apremilast (CC-10004) is an oral phosphodiesterase enzyme (PDE) inhibitor. It is highly 
selective for PDE4, which is the dominant PDE in inflammatory cells. Through inhibiting PDE4, 
apremilast elevates intracellular cyclic adenosine monophosphate (cAMP) levels, leading to a 
partial inhibition of the production of many pro-inflammatory mediators, as well as an increase 
in some anti-inflammatory mediators. A recent study in subjects with PsA indicated that 
apremilast was associated with reductions in TNF-, IL-17, IL-23, IL-6, IL-8, MIP-1, and 
MCP-1, as well as increases in anti-inflammatory mediators, including IL-10 and the IL-1 
receptor antagonist. It is believed, therefore, that apremilast exerts its therapeutic benefits 
through the modulation of multiple inflammatory pathways (Schafer, 2015).   
Following a comprehensive clinical development program, apremilast has been approved for the 
treatment of PsA and Psoriasis. It is under clinical investigation for the treatment of Behçet’s 
Syndrome and inflammatory bowel disease.  
Apremilast has been shown to be safe and efficacious in reducing signs and symptoms of PsA, as 
well as improving physical function (Cutolo, 2016; Edwards, 2016; Kavanaugh, 2014; Nash, 
2018). Like most agents, the clinical development program of apremilast was restricted to 
subjects with  3 swollen and  3 tender joints at baseline. This allowed for a limited proportion 
of subjects with asymmetric oligoarthritis at study entry. Consequently, the safety and efficacy of 
apremilast in patients with oligoarthritis remains to be further investigated.  
The current study is designed to evaluate the benefit:risk profile of apremilast in subjects with an 
early diagnosis of PsA ( 5 years since signs and symptoms began), presenting with 
oligoarthritis, despite initial stable treatments with either NSAIDs and/or  1  csDMARD 
(methotrexate [MTX] or sulfasalazine [SSZ]). 
Objectives 
Primary Objective 
 To evaluate the efficacy of apremilast 30 mg BID  NSAIDs and/or csDMARDs vs. 
Placebo  NSAIDs and/or csDMARDs in subjects with early oligoarticular PsA, 
assessed by modified MDA (MDA-Joints). 
Secondary Objectives  
 To evaluate the impact of treatment with apremilast 30 mg BID  NSAIDs and/or 
csDMARDs vs. Placebo  NSAIDs and/or csDMARDs on disease activity in subjects 
with early oligoarticular PsA, 
 To evaluate the impact of apremilast 30 mg BID  NSAIDs and/or csDMARDs vs. 
Placebo  NSAIDs and/or csDMARDs on patient reported outcomes (PROs) in 
subjects with early oligoarticular PsA, 
 To evaluate the safety and tolerability of apremilast 30 mg BID  NSAIDs and/or 
csDMARDs vs. Placebo  NSAIDs and/or csDMARDs in subjects with early 
oligoarticular PsA. 

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Exploratory Objectives 
Study Design 
This is a Phase 4, multicenter, randomized, double-blind, placebo-controlled, parallel-group 
study to evaluate the efficacy, safety and tolerability of apremilast (CC-10004) in subjects with 
early ( 5 years since signs and symptoms began) oligoarticular PsA (according to 
Classification Criteria for Psoriatic Arthritis [CASPAR] criteria), despite treatment with 
either NSAIDs and/or  2 csDMARD. Approximately 285 subjects will be randomized (2:1) to 
apremilast 30 mg BID or placebo. Treatment assignment will be stratified via an Interactive Web 
Response System (IWRS) based on concomitant use of glucocorticosteroids at baseline (yes/no) 
and prior/concomitant use of a csDMARD, either MTX or SSZ, (ie, csDMARD-naïve; 
csDMARD use prior to baseline [treatment not continued]; or csDMARD use prior to and 
concomitant at baseline). The number of subjects who are csDMARD-naïve is targeted to 
comprise up to 50  of the subjects enrolled in the study. Given that this is a phase 4 study, all 
subjects are required to meet the existing apremilast regulatory labeling conditions specific to the 
countries where enrollment will take place (eg, Food and Drug Administration [FDA], European 
Medicines Agency [EMA], Health Canada). There is no planned protocol extension following 
the end of the study.  
Subjects will be enrolled in this study if they received  2 prior csDMARD for the treatment of 
PsA. All subjects will be permitted to take NSAIDs and/or low-dose oral glucocorticosteroids 
(prednisone  10 mg/day or equivalent) throughout the study. The NSAIDs and low-dose oral 
glucocorticosteroids must be administered as a stable regimen for at least 2 weeks and 4 weeks 
prior to the Baseline Visit, respectively. A maximum of 1 concomitant use of csDMARD will be 
permitted if the subject is on a stable regimen for at least 3 months prior to the Baseline Visit. 
Stable doses of glucocorticosteroids, NSAIDs, and a csDMARD must be continued from the 
Baseline Visit through the Week 24 Visit. During this phase of the study, any change in dose, 
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 glucocorticosteroids, NSAIDs, or 
csDMARDs may be adjusted as clinically required.  
Subjects with prior exposure to biologic DMARD (bDMARD) and/or JAK-inhibitors will not be 
allowed in the study.  
This is a 56-week study. Subjects will have up to 4 weeks in the Screening Phase, followed by 
24 weeks in the Double-blind, Placebo-controlled Treatment Phase, which provides an 

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opportunity for “early escape” at Week 16. At the Week 24 Visit, subjects will be offered to 
enter the Active-treatment Extension Phase. All subjects enrolled in the Extension Phase will 
receive treatment with apremilast (30 mg BID) until the end of the study (ie, up to the Week 48 
Visit) or until early discontinuation.  
Beginning at the Week 28 Visit, all subjects in the Extension Phase will be dispensed open-label 
apremilast (30 mg BID) in high-density polyethylene (HDPE) bottles. The original treatment 
assignments (apremilast 30 mg BID or placebo) will remain blinded until the end of the study 
(Section 3.1). Subjects may also discontinue at any time during the study. 
The study will consist of 4 phases: 
 Screening Phase – up to 4 weeks 
 Randomized, Double-blind, Placebo-controlled Treatment Phase – Weeks 0 to 24. 
Henceforth, this will be referred to as the Placebo-controlled Phase.  
– Subjects will be randomly assigned in a 2:1 ratio to either apremilast 30 mg BID 
or placebo.  Subjects randomized to apremilast will be dose-titrated in a blinded 
fashion.  
– Dose titration is described in Study Treatments, Section 7.2 and Section 7.3. 
– Early Escape: Subjects with no improvement in SJC (sentinel joints) at Week 16 
are eligible for early escape, at the discretion of the Investigator and will receive 
apremilast 30 mg BID. The joints monitored for early escape must be the 
“sentinel joints” (ie, the joints affected at baseline).   
– Placebo-treated subjects who escape early will be transitioned to apremilast 30 
mg BID in a blinded fashion via an Interactive Web Response System (IWRS), 
while apremilast-treated subjects will remain on their original treatment 
assignment. Placebo-treated subjects will be dose-titrated in a blinded fashion. 
– All subjects who complete this 24-week treatment phase will have the option to 
enter the Active-treatment Extension Phase.  
 Active-treatment Extension Phase – Week 24 to Week 48. Henceforth, this will be 
referred to as the Extension Phase.  
– All subjects will receive apremilast 30 mg BID until the completion of the study 
(ie, up to the Week 48 Visit). The remaining placebo-treated subjects will be 
dose-titrated in a blinded fashion. 
– Beginning at the Week 28 Visit, all subjects in the Extension Phase will be 
dispensed open-label apremilast (30 mg BID) as described in Study Treatments 
and Section 7.3. 
 Post-treatment Observational Follow-up Phase – up to 4 weeks. Henceforth this will 
be referred to as the Observational Follow-up Phase. 
– All subjects who complete the Placebo-controlled Phase, the Extension Phase or 
prematurely discontinued from the study will participate in the 4-week 
Observational Follow-up Phase.  

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– The Observational Follow-up Visit should be performed 4 weeks after the last 
dose of investigational product (IP) ( 7 days). 
The study will be conducted in compliance with the International Council for Harmonisation 
(ICH) Good Clinical Practice (GCP). 
Study Population 
The study population will consist of male or female subjects,  18 years of age at the time of 
signing the informed consent form (ICF), with early ( 5 years since signs and symptoms 
began) oligoarthritis ( 1 swollen joint [SJ] but  4 SJs, and  1 tender joint [TJ] but  4 TJs at 
the Screening Visit and confirmed prior to randomization at the Baseline Visit), despite prior 
treatment with either NSAIDs (stable  2 weeks prior to the Baseline Visit) and/or  2 
csDMARD (stable regimen for  3 months prior to the Baseline Visit) for the treatment of PsA. 
See Inclusion Criteria, Section 4.2 and Permitted Concomitant Medications, Section 8.1 for 
details describing allowed PsA medications and dosing regimens. At Screening, subjects must 
have a documented diagnosis of PsA, based on the CASPAR, with a disease duration since 
diagnosis  3 months and  5 years. Subjects with prior exposure to biologic DMARD 
(bDMARD) and/or JAK-inhibitors will not be allowed in the study. 
No adjustment to NSAIDs or csDMARD dosing regimens will be allowed until Week 24. 
Between Week 24 and Week 48, dosing of concomitant medications may be adjusted as 
clinically required. The complete list of Inclusion and Exclusion criteria can be found in 
Section 4.2 and Section 4.3, respectively. Additional allowed PsA medications (including 
glucocorticosteroids, MTX and SSZ) and dosing regimens are described in Section 8.1. 
Length of Study  
Subjects will spend up to a total of 56 weeks in this study, up to 28 days (approximately, 
4 weeks) in the Screening Phase, 24 weeks in the Placebo-controlled Phase, 24 weeks in the 
Extension Phase, and 4 weeks in the Observational Follow-up Phase.  
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up, or the date of receipt of the last data point from the last subject that is 
required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, 
whichever is the later date. 
Study Treatments 
Eligible subjects will enter the Placebo-controlled Phase at the Baseline Visit. Subjects will be 
assigned randomly to apremilast 30 mg twice daily (BID) or placebo BID. Subjects are to take 
investigational product (IP), as designated in the treatment card, twice daily (morning and 
evening, approximately 12 hours apart, with or without food). 
With the aim to mitigate potential dose-related side effects associated with apremilast, such as 
headache and gastrointestinal (GI) disturbances, apremilast-treated subjects will be dose-titrated 
from 10 mg BID to 20 mg BID to 30 mg BID over the first 5 days of treatment (Table 14). 
Subjects assigned to placebo will receive 10-, 20-, and 30-mg placebo tablets in blister cards 
(treatment cards) which are identical in appearance to the corresponding strength apremilast 
tablets. Apremilast will be provided in blister cards as either 10 mg, 20 mg or 30 mg tablets. The 

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5-day titration period will also be initiated for the placebo arm after the following visits: the 
Baseline, Week 16 (early escape), and Week 24. The original treatment assignments (apremilast 
30 mg BID or placebo) will remain blinded throughout the study. 
At the Week 16 Visit, subjects with no improvement in SJC (sentinel joints) at Week 16 are 
eligible for early escape, at the discretion of the Investigator and will receive early escape 
treatment with apremilast 30 mg BID. The joints monitored for early escape must correspond to 
those affected at the Baseline Visit (sentinel joints). Refer to Section 4.2; Inclusion 6. Subjects 
will receive the following treatment: 
o Subjects who were randomized to apremilast (30 mg BID) at the Baseline Visit will 
continue to take apremilast 30 mg BID. 
o Subjects who were randomized to placebo at the Baseline Visit will be switched to 
receive apremilast (30 mg BID) and will be dose-titrated as described above.   
After the Week 24 Visit, subjects will be offered to enter the Active treatment Extension Phase. 
All subjects enrolled in the Extension Phase will receive treatment with apremilast (30 mg BID) 
until the end of the study (ie, up to the Week 48 Visit) or until early discontinuation. Placebo 
subjects will be dose titrated. All subjects will receive treatment cards of identical appearance to 
maintain the blinding of the original treatment assignments (apremilast 30 mg BID or placebo). 
Beginning at the Week 28 Visit, after placebo-treated subjects have completed the blinded 
titration period, all subjects in the Extension Phase will be dispensed open-label apremilast (BID) 
in high-density polyethylene (HDPE) bottles. Subjects must be clearly instructed to follow 
dosing instructions. The original treatment assignments (apremilast 30 mg BID or placebo) will 
remain blinded until the end of the study (Section 3.1). Subjects may also discontinue at any time 
during the study. 
Overview of Key Efficacy Assessments 
The following will be used for assessing efficacy: 
 Modified Minimal Disease Activity (MDA-Joints) 
➢ Based on achieving 1 swollen joint count (SJC) and  1 tender joint count (TJC; 
66/68 SJ/TJ counts), plus 3 out of 5 of the following cut-off values: Body Surface 
Area (BSA)  3, Patient pain assessment (Visual analog scale [VAS])  15, 
Patient global assessment of disease activity (VAS)  20, HAQ  0.5, Tender 
entheseal points  1 (Based on the Leeds Enthesitis Index - LEI).  
 Swollen and Tender Joint Counts 
 Evaluator’s (Physician’s) Global Assessments of Disease Activity on VAS scale 
 Patient’s (Subject’s) Global Assessments of Disease Activity on VAS  
 Patient’s (Subject’s) Pain Assessment on VAS  
 Health Assessment Questionnaire – Disability Index (HAQ-DI)  
 The Leeds Enthesitis Index (LEI) 
 

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 Number of digits affected by dactylitis 
 Clinical Disease Activity in Psoriatic Arthritis (cDAPSA) remission score 
(cDAPSA4) or low disease activity score (4cDAPSA13). cDAPSA calculation 
based on SJC, TJC (66/68 SJ/TJ counts), Patient pain assessment (VAS) and Patient 
global assessment of disease activity (VAS).  
 Measure of Very Low Disease Activity (VLDA) defined as achieving 1 SJC and 1 
TJC (66/68 SJ/TJ counts), plus all 5 of the following cut-off values: BSA  3, 
Patient pain assessment (VAS)  15, Patient global assessment of disease activity 
(VAS)  20, HAQ  0.5, Tender entheseal points  1 (based on the Leeds Enthesitis 
index - LEI) 
 Psoriatic Arthritis Disease Activity Score (PASDAS) to assess good or moderate 
response.  
 Plaque psoriasis assessment by Body Surface Area (BSA) 
Overview of Patients’ Reported Outcomes  
The following will be used for assessing health-related quality of life: 
 Psoriatic Arthritis Impact of Disease 12 questions (PsAID-12) questionnaire 
 
The following will be used for assessing safety: 
 Adverse events 
 Physical examination, vital signs, weight 
 Clinical laboratory evaluations 

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Statistical Methods  
Assuming a 15 dropout rate during the Randomized, Placebo-controlled, Double-blind 
Treatment Phase, a sample size of approximately
 for the active and placebo groups, 
respectively, will have 80 power to detect a true 15 difference (30 versus 15) in the 
proportions of subjects achieving the modified MDA between the treatment groups, using a chi-
square test with a two-sided significance level of 0.05. The primary efficacy endpoint, proportion 
of subjects who achieve the modified MDA at Week 16, between the treatment groups will be 
compared using a Cochran-Mantel-Haenszel (CMH) test, controlling for concomitant use of 
glucocorticosteroids at baseline (yes/no) and use of a csDMARD (csDMARD-naïve; csDMARD 
use prior to baseline; or csDMARD use prior to and concomitant at baseline). 

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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
PROTOCOL SUMMARY ...............................................................................................................4 
1. 
INTRODUCTION ......................................................................................................19 
1.1. 
Disease Background ...................................................................................................19 
1.1.1. 
Psoriatic Arthritis ........................................................................................................19 
1.2. 
Compound Background ..............................................................................................20 
1.2.1. 
Key Findings from Clinical Studies ...........................................................................21 
1.2.1.1. 
Efficacy .......................................................................................................................22 
1.2.1.2. 
Safety ..........................................................................................................................31 
1.3. 
Rationale .....................................................................................................................36 
1.3.1. 
Study Rationale and Purpose ......................................................................................36 
1.3.1.1. 
Unmet Medical Need ..................................................................................................36 
1.3.1.2. 
Rationale for the Study Design ...................................................................................36 
1.3.1.3. 
Rationale for Dose, Schedule, and Regimen Selection ..............................................36 
1.3.1.4. 
Rationale for Choice of Comparator Compounds ......................................................37 
2. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................38 
3. 
OVERALL STUDY DESIGN ....................................................................................44 
3.1. 
Study Design ...............................................................................................................44 
3.2. 
Study Duration for Subjects ........................................................................................47 
3.3. 
End of Trial .................................................................................................................47 
4. 
STUDY POPULATION .............................................................................................48 
4.1. 
Number of Subjects ....................................................................................................48 
4.2. 
Inclusion Criteria ........................................................................................................48 
4.3. 
Exclusion Criteria .......................................................................................................49 
5. 
TABLE OF EVENTS .................................................................................................51 
6. 
PROCEDURES ..........................................................................................................56 
6.1. 
Screening Period .........................................................................................................56 
6.2. 
Treatment Period ........................................................................................................58 
6.2.1. 
End of Treatment ........................................................................................................58 
6.3. 
Observational Follow-up ............................................................................................59 
6.3.1. 
Safety Follow-up ........................................................................................................59 

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6.4. 
Efficacy Assessments .................................................................................................60 
6.4.1. 
Modified Minimal Disease Activity–Joints (MDA-Joints) and its 
Components ................................................................................................................60 
6.4.1.1. 
Joint Assessment .........................................................................................................60 
6.4.1.2. 
Patient’s Global Assessments of Disease Activity .....................................................60 
6.4.1.3. 
Patient’s Pain Visual Analogue Scale .........................................................................60 
6.4.1.4. 
HAQ-DI ......................................................................................................................61 
6.4.1.5. 
Enthesitis: Leeds Enthesitis Index ..............................................................................61 
6.4.1.6. 
BSA.............................................................................................................................61 
6.4.1.7. 
Physician’s Global Assessments of Disease Activity .................................................61 
6.4.2. 
Enthesitis: 
 .........................................................................................61 
6.4.3. 
Dactylitis .....................................................................................................................62 
6.4.4. 
Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) ............................62 
6.4.5. 
Psoriatic Arthritis Disease Activity Score (PASDAS) ...............................................62 
6.4.6. 
High sensitivity C-reactive Protein .............................................................................62 
6.5. 
Safety Assessments .....................................................................................................63 
6.5.1. 
Serum and Urine Pregnancy Tests for Females of Childbearing Potential ................63 
6.5.2. 
Vital Signs, Height and Weight ..................................................................................63 
6.5.3. 
Complete/Limited Physical Examination ...................................................................63 
6.5.4. 
Psychiatric Evaluation ................................................................................................64 
6.5.5. 
Diarrhea, Nausea and Vomiting .................................................................................64 
6.5.6. 
Tuberculosis ................................................................................................................65 
6.5.7. 
Clinical Laboratory Evaluations .................................................................................65 
6.5.8. 
Adverse Events ...........................................................................................................65 
6.6. 
Patient Reported Outcomes or Quality of Life or Health Economics ........................65 
6.6.1. 
The PsA Impact of Disease 12-Item (PsAID-12) Questionnaire ................................66 

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7. 
DESCRIPTION OF STUDY TREATMENTS ..........................................................68 
7.1. 
Description of Investigational Product(s) ...................................................................68 
7.2. 
Treatment Administration and Schedule ....................................................................68 
7.3. 
Method of Treatment Assignment ..............................................................................70 
7.4. 
Packaging and Labeling ..............................................................................................70 
7.5. 
Investigational Product Accountability and Disposal .................................................71 
7.6. 
Study Medication Dispensing and Counting ..............................................................71 
7.7. 
Investigational Product Compliance ...........................................................................71 
7.8. 
Overdose .....................................................................................................................72 
8. 
CONCOMITANT MEDICATIONS AND PROCEDURES ......................................73 
8.1. 
Permitted Concomitant Medications and Procedures .................................................73 
8.2. 
Concomitant Medications Not Recommended ...........................................................74 
8.3. 
Prohibited Concomitant Medications and Procedures ................................................74 
8.4. 
Required Concomitant Medications and Procedures ..................................................75 
9. 
STATISTICAL CONSIDERATIONS .......................................................................76 
9.1. 
Overview .....................................................................................................................76 
9.2. 
Study Population Definitions ......................................................................................76 
9.3. 
Sample Size and Power Considerations .....................................................................76 
9.4. 
Background and Demographic Characteristics ..........................................................76 
9.5. 
Subject Disposition .....................................................................................................77 
9.6. 
Efficacy Analysis ........................................................................................................77 
9.6.1. 
Efficacy Evaluation for the Placebo-Controlled, Double-Blind Treatment 
Phase ...........................................................................................................................77 
9.6.2. 
Multiplicity .................................................................................................................77 
9.6.3. 
Primary Efficacy Endpoint .........................................................................................77 
9.6.4. 
Secondary Endpoints ..................................................................................................78 
9.6.5. 
Active-Treatment Phase. .............................................................................................78 
9.7. 
Safety Analysis ...........................................................................................................78 
9.8. 
Interim Analysis ..........................................................................................................78 
9.9. 
Other Topics ...............................................................................................................79 
9.9.1. 
Investigational Product Compliance (Tablets) ...........................................................79 

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9.9.2. 
Concomitant Therapy .................................................................................................79 
10. 
ADVERSE EVENTS..................................................................................................80 
10.1. 
Monitoring, Recording and Reporting of Adverse Events .........................................80 
10.1.1. 
Monitoring, Recording and Reporting AEs of Diarrhea ............................................80 
10.2. 
Evaluation of Adverse Events ....................................................................................80 
10.2.1. 
Seriousness .................................................................................................................81 
10.2.2. 
Severity/Intensity ........................................................................................................82 
10.2.3. 
Causality .....................................................................................................................83 
10.2.4. 
Duration ......................................................................................................................83 
10.2.5. 
Action Taken ..............................................................................................................83 
10.2.6. 
Outcome ......................................................................................................................83 
10.3. 
Abnormal Laboratory Values .....................................................................................83 
10.4. 
Pregnancy ...................................................................................................................84 
10.4.1. 
Collection of Pregnancy and Infant Health Information ............................................84 
10.4.2. 
Male Subjects With Partners Who Become Pregnant ................................................85 
10.4.3. 
Collection of Lactation Information ...........................................................................85 
10.5. 
Reporting of Serious Adverse Events .........................................................................85 
10.5.1. 
Safety Queries .............................................................................................................86 
10.6. 
Expedited Reporting of Adverse Events .....................................................................86 
11. 
DISCONTINUATIONS .............................................................................................88 
11.1. 
Treatment Discontinuation .........................................................................................88 
11.2. 
Study Discontinuation ................................................................................................88 
12. 
EMERGENCY PROCEDURES ................................................................................89 
12.1. 
Emergency Contact .....................................................................................................89 
12.2. 
Emergency Identification of Investigational Products ...............................................89 
13. 
REGULATORY CONSIDERATIONS......................................................................90 
13.1. 
Good Clinical Practice ................................................................................................90 
13.2. 
Investigator Responsibilities .......................................................................................90 
13.3. 
Subject Information and Informed Consent ...............................................................91 
13.4. 
Confidentiality ............................................................................................................91 
13.5. 
Protocol Amendments ................................................................................................91 
13.6. 
Institutional Review Board/Independent Ethics Committee Review and 
Approval .....................................................................................................................91 

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13.7. 
Ongoing Information for Institutional Review Board/ Ethics Committee .................92 
13.8. 
Termination of the Study ............................................................................................92 
14. 
DATA HANDLING AND RECORDKEEPING .......................................................93 
14.1. 
Data/Documents .........................................................................................................93 
14.2. 
Data Management .......................................................................................................93 
14.3. 
Record Retention ........................................................................................................93 
15. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................95 
15.1. 
Study Monitoring and Source Data Verification ........................................................95 
15.2. 
Audits and Inspections ................................................................................................95 
15.3. 
Product Complaint ......................................................................................................95 
15.3.1. 
How to Report a Product Complaint to Amgen: ........................................................96 
16. 
PUBLICATIONS .......................................................................................................97 
17. 
REFERENCES ...........................................................................................................98 
18. 
APPENDICES ..........................................................................................................102 
Appendix A: Table of Abbreviations ........................................................................................102 
Appendix B: The CASPAR Criteria .........................................................................................106 
Appendix C: Modified Minimal Disease Activity (MDA-Joints) Assessment .........................107 
Appendix D: Joint Assessment - 68 and 66 Joint Counts .........................................................108 
Appendix E: Visual Analog Scale .............................................................................................110 
Appendix F: Disability Index of the Health Assessment Questionnaire (HAQ-DI) .................111 
Appendix G: Leeds Enthesitis Index (LEI) ...............................................................................113 
Appendix H: Body Surface Area (BSA) ...................................................................................114 
Appendix K: C-Disease Activity index for Psoriatic Arthritis (cDAPSA) ...............................117 
Appendix L: Psoriatic Arthritis Disease Activity Score (PASDAS) ........................................118 
Appendix N: The PsA Impact of Disease 12-Item (PsAID-12) Questionnaire ........................120 

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Appendix T: Blister Card Configurations .................................................................................135 
Appendix W: Sample Serious Adverse Event Report Form .....................................................139 
Appendix X: Pregnancy Notification Form ..............................................................................142 
Appendix Y: Lactation Notification Form ................................................................................143 
 

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LIST OF TABLES 
Table 1: 
Apremilast Phase 3 and 3b Studies .............................................................................21 
Table 2: 
Primary (ACR20) and Major Secondary Endpoints of Studies 
CC-10004-PSA-002 (Palace 1), CC-10004-PSA-003 (Palace 2), and 
CC-10004-PSA-004 (Palace 3) (Full Analysis Set) ...................................................23 
Table 3: 
Primary and Major Secondary Endpoints of Study CC-10004-PSA-005 (Full 
Analysis Set) ...............................................................................................................26 
Table 4: 
Summary of Secondary Efficacy Endpoints Related to Enthesitis and 
Dactylitis at Weeks 16 (FAS; LOCF), Study CC 10004 PSA-005 ............................27 
Table 5: 
ACR 20/50/70 Responses at Weeks 16 and 24 During the Placebo-
Controlled Period (FAS; NRI), CC-10004-PSA-006 .................................................29 
Table 6: 
HAQ-DI Score (0 to 3) Change From Baseline at Weeks 16 and 24 (FAS; 
MMRM) ......................................................................................................................29 
Table 7: 
Gladman Enthesitis Index Change From Baseline at Weeks 16 and 24 
During the Placebo-Controlled Period in Subjects With Pre-existing 
Enthesopathy (FAS; MMRM) ....................................................................................30 
Table 8: 
Treatment-Emergent Adverse Events Reported in  2 of Subjects in Any 
Treatment Group, First 16 Weeks of Exposure (Studies CC-10004-PSA-002, 
CC-10004-PSA-003, CC-10004-PSA-004, and CC-10004-PSA-005; 
Subjects as Treated) ....................................................................................................32 
Table 9: 
Treatment-Emergent Serious Adverse Events Reported in  1 Subject in Any 
Treatment Group, First 16 Weeks of Exposure (Studies CC-10004-PSA-002, 
CC-10004-PSA-003, CC-10004-PSA-004, and CC-10004-PSA-005; 
Subjects as Treated) ....................................................................................................33 
Table 10: Frequency of Common AEs Over 208 Weeks of Exposure .......................................35 
Table 11: Study Objectives .........................................................................................................38 
Table 12: Study Endpoints ..........................................................................................................39 
Table 13: Table of Events ...........................................................................................................51 
Table 14: Treatment of Schema for Dose Titration at Baseline .................................................69 
Table 15: Treatment Schema for Dose Titration at Week 16 (Early Escape) or Week 24 .........69 
 
LIST OF FIGURES 
Figure 1: 
Overall Study Design ..................................................................................................46 
 

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1. 
INTRODUCTION 
1.1. 
Disease Background 
1.1.1. 
Psoriatic Arthritis 
Psoriatic arthritis (PsA) is a heterogeneous inflammatory rheumatologic disorder characterized 
by inflammatory arthritis affecting 6 to 39 of patients suffering from psoriasis. PsA is 
classified as a seronegative spondyloarthropathy (SpA) because it shares certain features with 
other conditions included in that group. Indeed, spinal involvement has been reported in up to 
50 of patients with PsA. In addition, PsA is associated with enthesitis and dactylitis, which are 
features common to SpA. Finally, the majority of patients with PsA are negative for rheumatoid 
factor (RF) (Gladman, 2005; Kruithof, 2005; Roberts, 1976). Moll and Wright described five 
subgroups of PsA (Moll, 1973). These include distal interphalangeal (DIP) joint only, 
asymmetrical oligoarthritis, polyarthritis, spondylitis and arthritis mutilans. Among these five 
subtypes, asymmetrical oligoarthritis sometimes involving distal interphalangeal (DIP) joints, is 
a frequent form of PsA (Ritchlin, 2017). Very little is known with respect to the burden of 
disease, the performance of different measurement tools and the appropriate management of 
patients with oligoarthritis. Indeed, there is a paucity data on the treatment of patients with 
oligoarthritis, one reason being that published clinical trials focus on polyarticular forms of the 
disease. In addition, treatment recommendations tend to focus on polyarticular forms (Gossec, 
2016). Knowledge regarding the efficacy of drugs in oligoarticular forms would be of great value 
to clinicians. 
Standard classification criteria for use in clinical studies remain to be established. In recent 
studies, patients with  4 active joint counts (tender and/or swollen) at baseline were classified as 
oligoarthritic (Coates, 2013; Helliwell, 2007; Jones, 1994; Kane, 2003). Use of this definition in 
different studies, indicated that the proportion of subjects with oligoarthritis ranges from 14 to 
63, the higher values being observed in patients with shorter disease duration. It is believed 
that the evolution of the disease, from oligoarthritis to polyarthritis, accounts for the lower 
proportion of patients with oligoarthritis in populations with longer disease duration. Indeed, 
results from the long-term follow-up of PsA cohorts, including subjects with short articular 
symptoms duration ( 24 months), showed that about two-thirds of subjects presenting with an 
oligoarthritic disease at baseline evolved into the polyarticular sub-type over time (Jones, 1994). 
In addition, treatments with conventional synthetic DMARDs (csDMARDs) were associated 
with the reclassification of subjects, from polyarthritic at the initial clinical presentation into 
oligoarthritic at follow-up (Kane, 2003). Such oligoarticular patients may be associated with 
residual joints that are less responsive to treatment when compared to patients with recent onset 
of oligoarthritis. Taken together, these observations suggest that patients with oligoarticular form 
of PsA but with long standing disease duration and previous response to anti-rheumatic 
treatments may be less sensitive to further improvement after additional therapies than earlier 
populations who are mainly csDMARDs-naive. As a result, the current study will enroll subjects 
with short disease duration and limited exposure to prior nonsteroidal anti-inflammatory drugs 
(NSAIDs) and/or csDMARDs. 
Results from the GRACE cohort (GRAPPA Composite Exercise) highlight the burden of disease 
of patients with oligoarthritis. The GRACE cohort enrolled 503 PsA patients, out of which 266 

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(53) were classified with oligoarthritis. This subpopulation of patients reported other aspects of 
the disease, such as enthesitis (34 of the patients) and dactylitis (12 of patients). Limited skin 
involvement was observed in these patients, as shown by a median Psoriasis Area and Severity 
Index (PASI) score of 1.2 points. Noteworthy, when comparing subjects with mono/oligoarthritis 
to polyarthritis, subjects with mono/oligoarthritis were associated with lower levels of 
inflammation and lower proportions of subjects with erosive disease at follow-up (Lindqvist, 
2008). 
The results from the Tight Control of Psoriatic Arthritis (TICOPA) trial in patients with early 
and treatment-naive PsA allowed for the comparison of outcomes measures between subjects 
with oligoarthritis and polyarthritis. Patients with oligoarthritis were more likely to achieve 
minimal disease activity (MDA) as defined by Coates, et al (Coates, 2010) than those with 
polyarticular disease. Conversely, a significantly greater proportion of subjects with polyarthritis 
achieved 20 improvement in the American College of Rheumatology ACR criteria (ACR 20) 
when compared with those with oligoarthritis (Coates, 2016). Further analyses of the TICOPA 
trial has shown that both Psoriatic Arthritis Disease Activity Score (PASDAS) and Composite 
Psoriatic Disease Activity Index have limited ability to distinguish effects of therapy in the 
subgroup of study patients with oligoarthritis (Coates, 2017). The value of the Clinical Disease 
Activity in Psoriatic Arthritis score (cDAPSA) [without measuring C-reactive protein], alone or 
in comparison to the MDA, has not been extensively studied in this subset of PsA patients. 
The limited performance of ACR20 response criteria reported in the TICOPA trial are inherent to 
the baseline level of disease activity associated with patients with oligoarthritis. This is partially 
explained by the limited discriminative ability of the ACR20 response criteria to report 20 
changes in populations with limited number of joint counts at baseline. For example, for a 
subject with 1 SJ and 1 TJ at baseline, a 20 improvement would correspond to a 0.2 reduction 
in 1 swollen joint (SJ) and 1 tender joint (TJ). This is not assessable by clinical palpation, 
making this endpoint less desirable for the studied population. As a result, the primary endpoint 
of the current study will be based on a modification of the MDA.  
1.2. 
Compound Background  
Apremilast (CC-10004) is an oral phosphodiesterase enzyme (PDE) inhibitor. It is highly 
selective for PDE4, which is the dominant PDE in inflammatory cells. Through inhibiting PDE4, 
apremilast elevates intracellular cyclic adenosine monophosphate (cAMP) levels, leading to a 
partial inhibition of the production of many pro-inflammatory mediators, as well as an increase 
in some anti-inflammatory mediators. Indeed, a recent study in subjects with PsA indicated that 
apremilast was associated with reductions in TNF-, IL-17, IL-23, IL-6, IL-8, MIP-1, and 
MCP-1, as well as increases in anti-inflammatory mediators, including IL-10 and the IL-1 
receptor antagonist. It is believed, therefore, that apremilast exerts its therapeutic benefits 
through the modulation of multiple inflammatory pathways (Schafer, 2015).  
Following a comprehensive clinical development program, apremilast has been approved for the 
treatment of PsA and Psoriasis. It is under clinical investigation for the treatment of Behçet’s 
Syndrome and inflammatory bowel disease.  

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Please refer to the Investigator’s Brochure for detailed information concerning the available 
pharmacology, toxicology, drug metabolism, clinical studies, and adverse event profile of the 
investigational product (IP). 
1.2.1. 
Key Findings from Clinical Studies 
The safety and efficacy of apremilast for the treatment of PsA were demonstrated in a 
comprehensive clinical development program. Subjects enrolled in Phases 3 and 3b studies 
included DMARD-naive, DMARDs-experienced, biologic-naive, and biologic-experienced 
subjects (Table 1). The results from these studies indicated that apremilast is safe and effective, 
both as monotherapy and in combination with csDMARDs.  
Table 1: 
Apremilast Phase 3 and 3b Studies 
Study 
Population 
Treatment Arms 
Subjects 
Randomized Who 
Received 1 Dose 
of Study 
Medication 
PALACE 1/ 
CC-10004-PSA
-002 
csDMARD- and/or 
biologic-experienced` 
Apremilast 20 mg/30 mg 
BID  concomitant 
csDMARDs vs. PBO  
concomitant csDMARDs 
504 
PALACE 2/ 
CC-10004-PSA
-003 
csDMARD- and/or 
biologic-experienced 
Apremilast 20 mg/30 mg 
BID  concomitant 
csDMARDs vs. PBO  
concomitant csDMARDs 
484 
PALACE 3/ 
CC-10004-PSA
-004 
csDMARD- and/or 
biologic-experienced 
with  1 psoriatic skin 
lesion  2 cm 
Apremilast 20 mg/30 mg 
BID  concomitant 
csDMARDs vs. PBO  
concomitant csDMARDs 
505 
PALACE 4/ 
CC-10004-PSA
-005 
csDMARD-naive and 
biologic-naive 
Apremilast monotherapy vs. 
PBO 
527 
ACTIVE/ 
CC-10004-PSA
-006 
Maximum 1 prior 
csDMARD, biologic-
naive 
Apremilast monotherapy vs. 
PBO 
219 

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1.2.1.1. 
Efficacy 
1.2.1.1.1. Efficacy Data From Phase 3 Studies CC-10004-PSA-002 (Palace 1), 
CC-10004-PSA-003 (Palace 2), and CC-10004-PSA-004 (Palace 3) Through 
Week 24 in Subjects With Prior csDMARDs and/or Biologic DMARDs 
Apremilast was first evaluated in 3 multicenter, randomized, double-blinded, placebo-controlled, 
Phase 3 pivotal studies (Studies CC-10004-PSA-002 [Palace 1], CC-10004-PSA-003 [Palace 2], 
and CC-10004-PSA-004 [Palace 3]; (Kavanaugh, 2014; Cutolo, 2016; Edwards, 2016). The 
studies were similarly designed. Adult patients with active PsA ( 3 swollen and  3 tender 
joints) despite prior csDMARD and/or biologic tumor necrosis factor (TNF) therapy were 
enrolled in the studies (TNF blockers efficacy failures were limited to  10 of subjects). 
Subjects were excluded if they had previously failed  3 agents for PsA or  1 TNF inhibitor. 
Stable concomitant methotrexate (MTX) ( 25 mg/week), sulfasalazine (SSZ [ 2 g/day]), 
leflunomide (LEF [ 20 mg/day]), low-dose oral corticosteroids (equivalent to  10 mg of 
prednisone a day), and/or nonsteroidal anti-inflammatory drugs (NSAIDs) were allowed during 
the trials.  
In the 3 pivotal studies, 1493 patients were randomized equally to placebo (N  496), apremilast 
(APR) 20 twice daily (BID (N  500), or APR 30 BID (N  497). Placebo patients whose tender 
and swollen joints counts had not improved by 20 were re-randomized 1:1 in a blinded 
fashion to either apremilast 20 mg or 30 mg twice daily at Week 16, while apremilast patients 
remained on their initial treatment.  
All 3 studies achieved their primary endpoint (Table 2); a statistically significantly higher 
percentage of subjects in the APR 30 BID treatment group achieved the primary endpoint of 
ACR 20 at Week 16 compared with placebo. Apremilast was also associated with statistically 
significant improvements in physical function and improvements in skin manifestations at Week 
16 and 24 among subjects with body surface area (BSA) for psoriasis  3  at baseline. 
Detailed information can be found in the Investigator’s Brochure (IB). 
 

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Table 2: 
Primary (ACR20) and Major Secondary Endpoints of Studies 
CC-10004-PSA-002 (Palace 1), CC-10004-PSA-003 (Palace 2), and 
CC-10004-PSA-004 (Palace 3) (Full Analysis Set) 
 
Study 
CC-10004-PSA-002 
Study CC-10004-PSA-
003 
Study CC-10004-PSA-
004 
 
Placebo 
N  168 
APR 30 
BID 
N  168 
Placebo 
N  159 
APR 30 
BID 
N  162 
Placebo 
N  169 
APR 30 
BID 
N  167 
ACR 20 – 
NRI 
 
 
 
 
 
 
Week 16, n 
() 
32 (19.0) 
64 (38.1) 
*** 
30 (18.9) 
52 (32.1) 
** 
31 (18.3) 
68 (40.7) 
*** 
Week 24, n 
() 
22 (13.1) 
59 (35.1) 
*** 
25 (15.7) 
40 (24.7)* 
26 (15.4) 
52 (31.3) 
*** 
ACR 50 – 
NRI 
 
 
 
 
 
 
Week 16, n 
() 
10 (6.0) 
27 
(16.1)** 
8 (5.0) 
17 (10.5) 
14 (8.3) 
25 (15.0) 
Week 24, n 
() 
7 (4.2) 
32 
(19.0)*** 
14 (8.8) 
19 (11.7) 
13 (7.7) 
27 (16.2)* 
ACR 70 – 
NRI 
 
 
 
 
 
 
Week 16, n 
() 
2 (1.2) 
7 (4.2) 
1 (0.6) 
2 (1.2) 
4 (2.4) 
6 (3.6) 
Week 24, n 
() 
1 (0.6) 
17 
(10.1)*** 
5 (3.1) 
4 (2.5) 
6 (3.6) 
9 (5.4) 
HAQ – 
LOCFa 
 
 
 
 
 
 
Week 16  
mean change 
from Baseline 
(SE)b 
-0.086 
(0.0360) 
-0.244 
(0.0364) 
** 
-0.053 
(0.0358) 
-0.193 
(0.0354) ** 
-0.065 
(0.0335) 
-0.192 
(0.0339) ** 
Week 24  
mean change 
from Baseline 
(SE)b 
-0.076 
(0.0369) 
-0.258 
(0.0371) 
*** 
-0.085 
(0.0377) 
-0.206 
(0.0372)* 
-0.053 
(0.0350) 
-0.192 
(0.0353) ** 

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Table 2: 
Primary (ACR20) and Major Secondary Endpoints of Studies 
CC-10004-PSA-002 (Palace 1), CC-10004-PSA-003 (Palace 2), and 
CC-10004-PSA-004 (Palace 3) (Full Analysis Set) (Continued) 
 
Study 
CC-10004-PSA-002 
Study CC-10004-PSA-
003 
Study CC-10004-PSA-
004 
BSA  3 at 
Baseline 
Placebo 
N  68 
APR 30 
BID 
N  82 
Placebo 
N  74 
APR 30 
BID 
N  77 
Placebo 
N  89 
APR 30 
BID 
N  90 
PASI 50 – 
LOCF 
 
 
 
 
 
 
Week 16, n 
() 
11 (16.2) 
36 
(43.9)*** 
10 (13.5) 
33 (42.9) 
*** 
22 (24.7) 
38 (42.2)* 
Week 24, n 
() 
12 (17.6) 
41 
(50.0)*** 
11 (14.9) 
35 (45.5) 
*** 
22 (24.7) 
39 (43.3)** 
PASI 75 - 
LOCF 
 
 
 
 
 
 
Week 16, n 
() 
3 (4.4) 
18 
(22.0)** 
2 (2.7) 
17 
(22.1)*** 
7 (7.9) 
20 (22.2)** 
Week 24, n 
() 
3 (4.4) 
17 
(20.7)** 
3 (4.1) 
21 
(27.3)*** 
10 (11.2) 
23 (25.6)** 
ACR 20/50/70  American College of Rheumatology 20/50/70 response; APR  apremilast; BID  twice 
daily; BSA  body surface area; HAQ-DI  Health Assessment Questionnaire Disability Index; PASI 50/75  
50/75 or greater improvement in the Psoriasis Area and Severity Index; LOCF  last observation carried 
forward; NRI  nonresponder imputation; PASI 50/75  50/75 or greater improvement in the Psoriasis Area and 
Severity Index; SE  standard error. 
a Subjects with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included. 
b Least-squares mean (SE) and p-value based on an analysis of covariance model for the change from baseline at the 
respective time point, with treatment group and baseline DMARD use as factors, and (for Study PSA-004 only) 
involvement of  3 BSA with psoriasis at baseline as factors, and the baseline value as a covariate. 
Note: ***p  0.001 for apremilast versus placebo. **p  0.01 for apremilast versus placebo. *p  0.05 for apremilast 
versus placebo. 
HAQ-DI score: 0  best, 3  worst; measures the subject’s ability to perform the following: dress/groom, arise, eat, 
walk, reach, grip, maintain hygiene, and maintain daily activity. 
For subjects who discontinued from the study prior to Week 16, the last available postbaseline value observed prior 
to discontinuation was carried forward to Weeks 16 and 24. For subjects who entered early escape (EE) at Week 16 
or who did not enter EE but discontinued from the study between Weeks 16 and 24, the last available postbaseline 
value observed prior to EE or discontinuation, respectively, was carried forward to Week 24. Missing values for 
subjects who did not discontinue or enter EE were imputed using the latest available postbaseline value prior to the 
visit in question. Subjects who did not have sufficient data (observed or imputed) for a determination of response 
status at the respective visits were counted as non-responders. 
 

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1.2.1.1.2. Efficacy Data From Phase 3 Study CC-10004-PSA-005 (Palace 4) Through 
Week 24 in Subjects Naive to csDMARDs and Biologic DMARDs 
The efficacy of apremilast in subjects naive to csDMARDs therapy was investigated in a 
multicenter, randomized, double-blinded, placebo-controlled Phase 3 study (CC-10004-PSA-005 
[Palace 4]; Wells, 2018). Subjects enrolled had a diagnosis of PsA for  3 months and active 
disease (defined by  3 swollen and  3 tender joints). Previous treatment with csDMARDs or 
biologics was not allowed. Subjects could receive stable doses of prednisone (equivalent to 
 10 mg/day) and/or NSAIDs. The use of other csDMARDs, including MTX, SSZ, LEF, or 
biologics was prohibited during the trial. Subjects were randomized 1:1:1 to placebo, 
APR 20 BID, or APR 30 BID treatment groups.  
In total, 527 subjects were randomized to the placebo (n  176), APR 20 BID (n  175), or 
APR 30 BID (n  176) group. Subjects whose tender and swollen joint counts had not improved 
by 20 at Week 16 were required to enter the early escape (EE) to blinded active treatment. 
Placebo subjects who met the EE criteria were re-randomized 1:1 in a blinded fashion to 
APR 20 BID or APR 30 BID. Apremilast subjects remained on their initial treatment.  
A statistically significantly higher percentage of subjects in the APR 30 BID treatment group 
achieved the primary endpoint of ACR 20 at Week 16 compared with placebo (Table 3). 
Apremilast was also associated with statistically significant improvements in physical function 
and improvements in skin manifestations at Week 16 and 24 among subjects with BSA for 
psoriasis  3 at baseline.  
Detailed information can be found in the IB. 
 

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Table 3: 
Primary and Major Secondary Endpoints of Study CC-10004-PSA-005 (Full 
Analysis Set) 
 
Study CC-10004-PSA-005 
 
Placebo 
N  176 
APR 30 BID 
N  176 
ACR 20 – NRI 
 
 
Week 16, n () 
28 (15.9) 
54 (30.7)** 
Week 24, n () 
23 (13.1) 
43 (24.4)** 
ACR 50 – NRI 
 
 
Week 16, n () 
8 (4.5) 
20 (11.4)* 
Week 24, n () 
11 (6.3) 
22 (12.5)* 
ACR 70 – NRI 
 
 
Week 16, n () 
2 (1.1) 
7 (4.0) 
Week 24, n () 
7 (4.0) 
8 (4.5) 
HAQ - LOCFa 
 
 
Week 16  
mean change from Baseline (SE)b 
0.012 (0.0350) 
-0.205 (0.0350)*** 
Week 24  
mean change from Baseline (SE)b 
0.012 (0.0370) 
-0.207 (0.0369)*** 
BSA  3 at Baseline 
Placebo 
N  93 
APR 30 BID 
N  103 
PASI 50 – LOCF 
 
 
Week 16, n () 
18 (19.4) 
51 (46.8)*** 
Week 24, n () 
23 (24.7) 
53 (48.6)*** 
PASI 75 – LOCF 
 
 
Week 16, n () 
10 (10.8) 
29 (26.6)** 
Week 24, n () 
11 (11.8) 
28 (25.7)* 
ACR 20/50/70  American College of Rheumatology 20/50/70 response; APR  apremilast; BID  twice daily; BSA  
body surface area; HAQ-DI  Health Assessment Questionnaire Disability Index; PASI 50/75  50/75 or greater 
improvement in the Psoriasis Area and Severity Index; LOCF  last observation carried forward; NRI  nonresponder 
imputation; SE  standard error.  
a Subjects with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included. 
b Least-squares mean (SE) and p-value based on an analysis of covariance model for the change from baseline at the respective 
time point, with treatment group and baseline DMARD use as factors, and (for Study PSA-004 only) involvement of  3 
BSA with psoriasis at baseline as factors, and the baseline value as a covariate. 

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Note: ***p  0.001 for apremilast versus placebo. **p  0.01 for apremilast versus placebo. *p  0.05 for apremilast versus 
placebo. 
HAQ-DI score: 0  best, 3  worst; measures the subject’s ability to perform the following: dress/groom, arise, eat, walk, reach, 
grip, maintain hygiene, and maintain daily activity. 
For subjects who discontinued from the study prior to Week 16, the last available postbaseline value observed prior to 
discontinuation was carried forward to Weeks 16 and 24. For subjects who entered early escape (EE) at Week 16 or who did not 
enter EE but discontinued from the study between Weeks 16 and 24, the last available postbaseline value observed prior to EE or 
discontinuation, respectively, was carried forward to Week 24. Missing values for subjects who did not discontinue or enter EE 
were imputed using the latest available postbaseline value prior to the visit in question. Subjects who did not have sufficient data 
(observed or imputed) for a determination of response status at the respective visits were counted as non-responders. 
Health Assessment Questionnaire–Disability Index (HAQ-DI) score:  0  best, 3  worst; 
measures the subject’s ability to perform the following: dress/groom, arise, eat, walk, reach, grip, 
maintain hygiene, and maintain daily activity. 
For subjects who discontinued from the study prior to Week 16, the last available postbaseline 
value observed prior to discontinuation was carried forward to Weeks 16 and 24. For subjects 
who entered EE at Week 16 or who did not enter EE but discontinued from the study between 
Weeks 16 and 24, the last available postbaseline value observed prior to EE or discontinuation, 
respectively, was carried forward to Week 24. Missing values for subjects who did not 
discontinue or enter EE were imputed using the latest available postbaseline value prior to the 
visit in question. Subjects who did not have sufficient data (observed or imputed) for a 
determination of response status at the respective visits were counted as non-responders. 
Improvements in enthesitis and dactylitis among subjects with baseline enthesitis and/or 
dactylitis at baseline are shown in Table 4. 
Table 4: 
Summary of Secondary Efficacy Endpoints Related to Enthesitis and 
Dactylitis at Weeks 16 (FAS; LOCF), Study CC 10004 PSA-005 
Secondary Endpoints 
Placebo 
N  176 
APR 30 BID 
N  176 
MASES change from baseline, LS mean (SE)  
-0.5 (0.24) 
-1.5 (0.25)** 
MASES  0, n () 
22 (19.1) 
41 (36.9)** 
Dactylitis change from baseline, LS mean (SE)  
-1.0 (0.25) 
-1.7 (0.26)* 
Dactylitis count  0, n () 
30 (33.3) 
34 (40.5) 
APR  apremilast; BID  twice daily; FAS  Full Analysis Set; LOCF  last observation carried forward; LS  least 
squares; MASES  Maastricht Ankylosing Spondylitis Enthesitis Score; SE  standard error.  
MASES evaluated only subjects with pre-existing enthesopathy (N  115 and 111 for placebo and APR 30 BID, 
respectively). 
Dactylitis score evaluated only in subjects in pre-existing dactylitis (N  90 and 84 for placebo and APR 30 BID, 
respectively). 
Note:. **p  0.01 for apremilast versus placebo. *p  0.05 for apremilast versus placebo.   
 

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1.2.1.1.3. Efficacy Data From Phase 3 CC-10004-PSA-006 (ACTIVE) Through Week 24 in 
Subjects With an Inadequate Response to 1 csDMARDs and Who Received 
Apremilast Monotherapy 
The rapid onset of efficacy of apremilast monotherapy in biologic-naive patients who had 
received 1 csDMARDs was demonstrated in the ACTIVE study (CC-10004-PSA-006; Nash, 
2018), a Phase 3b multicenter, parallel-group study with 1 active treatment; overall treatment 
duration was 2 years. The study randomized 219 patients (APR 30 mg, n110; PBO, n109). At 
Week 16 (time of the primary endpoint), all subjects whose improvement was 10 in both 
tender and swollen joint counts were eligible to enroll into an EE to active treatment with 
apremilast 30 mg BID. After 24 weeks of treatment, all subjects entered the active-treatment 
phase, in which they received apremilast 30 mg BID.  
A separation in the proportion of ACR20 responders to APR vs PBO was noted at Week 2 
(16.4 vs 6.4; P  0.0252), the first post-baseline visit. Early onset of response to APR was 
observed across clinical assessments, with improvements in DAS-28 (CRP), SJC, HAQ-DI, 
enthesitis, and morning stiffness severity. Dactylitis and skin responses were not assessed in 
CC-10004-PSA-006. 
A statistically significantly greater proportion of subjects in the APR 30 BID treatment group 
achieved the primary endpoint of ACR 20 response at Week 16 compared to placebo. A 
nominally significantly greater proportion of subjects in the APR 30 BID treatment group 
achieved an ACR 50 or ACR 70 response at Week 16 than in the placebo group (Table 5). 
Significant reductions in PsA disease activity/manifestations vs placebo were also demonstrated 
by changes in DAS-28 (CRP) (P  0.0001), SJC (P  0.0001), and HAQ-DI (Table 6). 
Detailed information can be found in the IB. 

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Table 5: 
ACR 20/50/70 Responses at Weeks 16 and 24 During the Placebo-Controlled 
Period (FAS; NRI), CC-10004-PSA-006  
 
Study CC-10004-PSA-006 
 
Placebo 
N  109 
APR 30 BID 
N  110 
ACR 20 
 
 
Week 16, n () 
22 (20.2) 
42 (38.2)** 
Week 24, n () 
27 (24.8) 
48 (43.6)** 
ACR 50 
 
 
Week 16, n () 
5 (4.6) 
20 (18.2)** 
Week 24, n () 
12 (11.0) 
22 (20.0) 
ACR 70 
 
 
Week 16, n () 
0 (0.0) 
7 (6.4)* 
Week 24, n () 
5 (4.6) 
8 (7.3) 
ACR 20/50/70  American College of Rheumatology 20/50/70; APR  apremilast; BID  twice daily; 
FAS  Full Analysis Set; NRI  nonresponder imputation. 
Note: **p  0.01 for apremilast versus placebo..*p  0.05 for apremilast versus placebo.   
 
Table 6: 
HAQ-DI Score (0 to 3) Change From Baseline at Weeks 16 and 24 (FAS; 
MMRM) 
Visit 
Treatment Group 
na 
Change From Baseline 
LS Mean (SE)b 
Week 16 
 
 
Placebo 
109 
-0.055 (0.0513) 
APR 30 BID 
109 
-0.205 (0.0523)* 
Week 24 
 
 
Placebo 
109 
-0.169 (0.0581) 
APR 30 BID 
109 
-0.273 (0.0572) 
APR  apremilast; BID  twice daily; DMARD  disease-modifying antirheumatic drug; EE  early escape; FAS  full analysis 
set; HAQ-DI  Health Assessment Questionnaire – Disability Index; LS  least-squares; MMRM  mixed-effects model of 
repeated measures; SE  standard error. 
a Subjects with a baseline value and at least 1 postbaseline value (after exclusion of data for EE subjects) during the 
Placebo-controlled Phase are included in the MMRM analysis. n with non-missing values were 103 and 91 for Placebo and 
APR 30 BID at Week 16, and 63 and 76 at Week 24, respectively. 
b The LS mean (SE) and 2-sided p-value are based on an MMRM analysis for the change from baseline, with treatment group, 
time, treatment-by-time interaction, and previous DMARD use and baseline oral corticosteroids (prednisone or equivalent) use 
as factors and the baseline value as a covariate. An unstructured covariance matrix that is homogeneous across treatment 
groups was used. The p-values in italics are  0.05 and are considered nominally significant, as hierarchical testing was stopped 
after the first secondary endpoint. 

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Among patients with enthesitis at Baseline, significant improvements from Baseline in Gladman 
Enthesitis Index (GEI) score were observed with APR 30 mg (-1.1) vs placebo (-0.4) at Week 2 
(P.0354), as well as at Weeks 16 and 24 (Table 7). 
In addition, numerically greater proportions of subjects treated with APR 30 mg (48.2) 
compared to placebo (33.3) achieved GEI scores of 0 at Week 24. 
 
Table 7: 
Gladman Enthesitis Index Change From Baseline at Weeks 16 and 24 During 
the Placebo-Controlled Period in Subjects With Pre-existing Enthesopathy 
(FAS; MMRM) 
Visit 
 
Treatment Group 
na 
Change From Baseline 
Week 16 
LS Mean (SE)b 
Week 24 
LS Mean (SE)b 
Placebo 
51 
-0.4 (0.26) 
-0.5 (0.27) 
APR 30 BID 
56 
-1.5 (0.26)** 
-1.5 (0.26)** 
APR  apremilast; BID  twice daily; DMARD  disease-modifying antirheumatic drug; EE  early escape; FAS  
Full Analysis Set; GEI  Gladman Enthesitis Index; LS  least squares; MMRM  mixed-effects model for repeated 
measures; SE  standard error.  
a Subjects with a baseline value and at least 1 postbaseline value at or prior to the respective visits are included. n 
with non-missing values were 48 and 49 for Placebo and APR 30 BID at Week 16, and 29 and 41 at Week 24, 
respectively. 
b The LS mean and 2-sided p-value is based on an MMRM analysis for the change from baseline, with treatment 
group, time, treatment-by-time interaction, and previous DMARD use and baseline oral corticosteroids 
(prednisone or equivalent) use as factors and the baseline value as a covariate. An unstructured covariance matrix 
that is homogeneous across treatment groups was used. The p-values in italics are  0.05 and are considered 
nominally significant, as hierarchical testing was stopped after the first secondary endpoint  
Note: **p  0.01 for apremilast versus placebo. For subjects who EE at Week 16, data obtained after EE are 
excluded from the MMRM analysis. The GEI is a count from 0 to 6. A higher count represents greater enthesitis 
burden, and a negative change from baseline indicates improvement. Pre-existing enthesopathy was defined as 
subjects who had a baseline GEI score of greater than 0. Joints temporarily or permanently unassessable at baseline 
were excluded from joint count. For other unassessed joints at baseline, the joint assessment at the Screening visit, if 
assessed, was used as the baseline assessment; otherwise, the joint was excluded from joint count. The last observed 
joint assessment (at baseline or postbaseline) is used for joints unassessed at the time point. 
1.2.1.1.4. Long term Efficacy Data From Phase 3 Study CC-10004-PSA-002 (Palace 1)  
The 5-year efficacy of apremilast in subjects with active PsA despite prior csDMARD and/or 
biologic anti-TNF therapy was assessed using data from the Phase 3 Study CC-10004-PSA-002 
(Palace 1) (TNF blockers efficacy failures were limited to  10 of subjects). Data were based 
on observed analyses from subjects who received apremilast 30 mg BID and who were still 
attending study visits.  
ACR20/50/70 responses were achieved by 71.7, 48.6, and 28.4 of subjects, respectively, 
attending the Week 260 Visit (Kavanaugh, 2018). Psoriasis Area and Severity Index (PASI) 50 
and 75 were achieved by 69.4 and 46.9 of subjects, respectively. At Week 260, 61.5 of the 
subjects achieved HAQ-DI improvements 0.3, which corresponds to the minimal clinically 
important difference (MCID) (Mease, 2004). 

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Apremilast was also associated with sustained responses and improvements in enthesitis and 
dactylitis among subjects still attending study visits. At 5 years, 54.5 of subjects achieved a 
Maastricht Ankylosing Spondylitis Enthesitis Score of 0 and 80 achieved a dactylitis count 
of 0. 
1.2.1.1.5. Long-term Efficacy Data From Phase 3 Study CC-10004-PSA-005 (Palace 4) in 
csDMARD-naive patients 
The long-term efficacy profile of APR monotherapy in DMARD-naïve subjects was reported for 
 208 weeks. ACR20/50/70 responses were achieved by 68.2, 43.4, and 23.1 of subjects, 
respectively, attending the Week 208 Visit (Wells, 2017). PASI 50 and 75 were achieved by 
67.6 and 40.5. At Week 208, half of the subjects achieved HAQ-DI improvements greater 
than 0.3, which corresponded to the MCID (Mease, 2004). 
Apremilast monotherapy was also associated with sustained responses and improvements in 
enthesitis and dactylitis among subjects still attending study visits.  
1.2.1.1.6. Long-term Efficacy Data From Phase 3 Study CC-10004-PSA-006 (ACTIVE)  
In biologic-naive PsA patients who may have had exposure to 1 prior csDMARD, sustained 
improvements were observed with the continued exposure to apremilast in monotherapy among 
subjects still attending study visits through Week 52: ACR20/50/70 responses were achieved by 
67.1, 36.7, and 21.3.0 respectively; also, 45.6 achieved HAQ-DI improvements  0.35, 
which corresponded to the MCID. It is noteworthy that 62.8 of subjects who were initially 
randomized to receive APR 30 mg with baseline enthesitis (GEI0) achieved a GEI of 0 at 
Week 52 (Nash, 2018). 
1.2.1.2. 
Safety 
1.2.1.2.1. Pooled Safety 16 Week Data From Phase 3 Studies CC-10004-PSA-002 
(Palace 1), CC-10004-PSA-003 (Palace 2), CC-10004-PSA-004 (Palace 3), and 
CC-10004-PSA-005 (Palace 4) 
The safety data from the Palace 1, 2, 3, and 4 studies were pooled and summarized for the first 
16 weeks of exposure to placebo or apremilast (Celgene, 2017; Wells, 2013). The analyses 
conducted on the apremilast population included subjects started on apremilast at baseline and 
subjects switched from placebo to apremilast at Weeks 16 or 24. Analysis included all data 
during the time subjects were exposed to apremilast, regardless of the time apremilast exposure 
started. 
Approximately half of the subjects (50.7) experienced 1 treatment-emergent adverse event 
(TEAE) during the first 16 weeks of exposure to apremilast. The incidence of TEAE was higher 
among subjects who received apremilast than placebo (42.9) (Table 8). The most frequently 
reported TEAEs were diarrhea, nausea, headache, and upper respiratory tract infection. The 
subject incidence of diarrhea, nausea, and headache was higher in the APR 30 BID group than in 
the APR 20 BID group, suggesting a dose effect.  
 

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Table 8: 
Treatment-Emergent Adverse Events Reported in  2 of Subjects in Any 
Treatment Group, First 16 Weeks of Exposure (Studies CC-10004-PSA-002, 
CC-10004-PSA-003, CC-10004-PSA-004, and CC-10004-PSA-005; Subjects 
as Treated) 
Preferred Terma 
Weeks 0 to 16 
First 16 Weeks of Apremilast Treatmentb 
Placebo 
Subjects 
n () 
(N  671) 
APR 20 BID 
n () 
(N  972) 
APR 30 BID 
n () 
(N  973) 
APR Total 
n () 
(N  1945) 
Any TEAE 
288 (42.9) 
470 (48.4) 
516 (53.0) 
986 (50.7) 
Diarrhea  
17 (2.5) 
86 (8.8) 
128 (13.2) 
214 (11.0) 
Nausea 
26 (3.9) 
71 (7.3) 
114 (11.7) 
185 (9.5) 
Headache 
24 (3.6) 
53 (5.5) 
77 (7.9) 
130 (6.7) 
Upper Respiratory Tract 
Infection  
16 (2.4) 
42 (4.3) 
37 (3.8) 
79 (4.1) 
Vomiting 
5 (0.7) 
17 (1.7) 
29 (3.0) 
46 (2.4) 
Nasopharyngitis 
12 (1.8) 
28 (2.9) 
17 (1.7) 
45 (2.3) 
Hypertension 
15 (2.2) 
17 (1.7) 
25 (2.6) 
42 (2.2) 
Dyspepsia 
8 (1.2) 
21 (2.2) 
19 (2.0) 
40 (2.1) 
Abdominal Pain Upper 
1 (0.1) 
19 (2.0) 
18 (1.8) 
37 (1.9) 
AE  adverse event; APR  apremilast; BID  twice daily; MedDRA  Medical Dictionary for Regulatory 
Activities; TEAE  treatment-emergent adverse event. 
a Preferred terms are coded using MedDRA Version 14 and are presented in descending order of subject incidence 
in the APR Total group. A subject with multiple occurrences of an AE is counted only once in the AE category. 
b The first 16 weeks of exposure are included regardless of when apremilast exposure started. 
 
Treatment-emergent AEs were predominantly mild or moderate in severity. The most frequently 
reported TEAEs (ie, diarrhea, nausea, upper respiratory tract infection, and headache) were 
primarily mild in severity. Severe diarrhea was reported by 1 (0.1) subject in the placebo 
group, 4 (0.4) in the APR 20 BID group, and 3 (0.3) in the APR 30 BID group. Severe 
nausea was reported by 0 subjects in the placebo group, 2 (0.2) in the APR 20 BID group, and 
3 (0.3) in the APR 30 BID group. Severe headache was reported by 1 (0.1) subject in the 
placebo group, 2 (0.2) in the APR 20 BID group, and 1 (0.1) in the APR 30 BID group. No 
events of severe upper respiratory tract infection were reported in any treatment group. 
Treatment with apremilast was associated with an increase in adverse reactions of depression. 
During the 0-to-16-week placebo-controlled period of Palace 1, 2, and 3, 1.0 (10/998) of 
patients treated with apremilast reported depression or depressed mood and 0.8 (4/495) treated 
with placebo. 

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Body weight was measured routinely in Studies CC-10004-PSA-002, CC-10004-PSA-003, 
CC-10004-PSA-004, and CC-10004-PSA-005. At the end of the placebo-controlled period, 
median (mean) weight change from baseline was 0.00 (0.13) kg in the placebo group, -0.50 
(-1.05) kg in the APR 20 BID group, and -0.60 (-0.97) kg in the APR 30 BID group. Weight loss 
 5 was observed in 2.1 of subjects in the placebo group, 4.7 in the APR 20 BID group, 
and 4.9 in the APR 30 BID group.  
Serious TEAEs were reported for 22 (3.3) subjects who received placebo and 44 (2.3) who 
received apremilast during the first 16 weeks of exposure (Table 9). The incidence of serious 
adverse events (SAEs) was comparable across treatment groups, ie, 3.3 of subjects in the 
placebo group, 2.4 in APR 20 BID group, and 2.2 in the APR 30 BID group. 
 
Table 9: 
Treatment-Emergent Serious Adverse Events Reported in  1 Subject in Any 
Treatment Group, First 16 Weeks of Exposure (Studies CC-10004-PSA-002, 
CC-10004-PSA-003, CC-10004-PSA-004, and CC-10004-PSA-005; Subjects 
as Treated) 
Preferred Terma 
Weeks 0 to 
16 
First 16 Weeks of Apremilast Treatmentb 
Placebo 
n () 
(N  671) 
APR 20 
BID 
n () 
(N  972) 
APR 30 
BID 
n () 
(N  973) 
APR Total 
n () 
(N  1945) 
Any SAE 
22 (3.3) 
23 (2.4) 
21 (2.2) 
44 (2.3) 
Atrial Fibrillation 
0 
0 
2 (0.2) 
2 (0.1) 
Acute Myocardial Infarction 
1 (0.1) 
2 (0.2) 
0 
2 (0.1) 
Deep Vein Thrombosis 
0 
0 
2 (0.2) 
2 (0.1) 
Myocardial Ischemia 
0 
2 (0.2) 
0 
2 (0.1) 
Psoriatic Arthropathy 
3 (0.4) 
1 (0.1) 
1 (0.1) 
2 (0.1) 
Hypertensive Crisis 
2 (0.3) 
0 
1 (0.1) 
1 (0.1) 
Pancreatitis Acute 
2 (0.3) 
0 
0 
0 
AE  adverse event; APR  apremilast; BID  twice daily; MedDRA  Medical Dictionary for Regulatory 
Activities; SAE  serious adverse event. 
a Preferred terms are coded using MedDRA Version 14 and are presented in descending order of subject incidence 
in the APR Total group and then alphabetically. A subject with multiple occurrences of an AE is counted only 
once in the AE category. 
b The first 16 weeks of exposure are included regardless of when apremilast exposure started. 
During the first 16 weeks, 1 death was reported in Study PSA-002 (Palace 1). The event occurred 
in a subject randomized to the APR 20 BID treatment group, who died due to multi-organ failure 
on Day 73 of the study. The subject was diagnosed with anemia due to vitamin B12 deficiency 
before the first dose of apremilast and was receiving concomitant MTX for the treatment of PsA. 

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The death certificate indicated that the direct cause of death was “multiple organ failure,” 
specifying that severe B12 deficiency anemia led to the event of multiple organ failure. 
TEAEs leading to drug withdrawal were reported in 3.6 of subjects in the placebo group, 4.5 
in the APR 20 BID group, and 5.2 in the APR 30 BID group. The most frequently reported 
TEAEs leading to withdrawal of apremilast were diarrhea, nausea, and headache. Among 
subjects who were taking placebo, the most frequently reported TEAEs that led to drug 
withdrawal were diarrhea and nausea. There was no evidence of an increased incidence of 
TEAEs leading to drug withdrawal with continued apremilast treatment when the incidence rate 
was adjusted for exposure. 
1.2.1.2.2. Long term Safety Data From CC-10004-PSA-006 (ACTIVE), CC-10004-PSA-
002 (Palace 1), CC-10004-PSA-003 (Palace 2) and CC-10004-PSA-004 (Palace 3)  
The long-term safety of apremilast monotherapy in patients who had received  1 csDMARD 
was assessed in the ACTIVE study over a period of 52 weeks (Nash, 2018). The overall 
incidence of AEs in the placebo-controlled period was generally similar for APR monotherapy 
and placebo. The most commonly reported AEs ( 5 of patients) with APR vs placebo were 
nasopharyngitis (8.3 vs 6.4, respectively), nausea (8.3 vs 1.8), headache (7.3 vs 3.7), 
hypertension (6.4 vs 6.4), and diarrhea (patient- or investigator-reported) (14.7 vs 11.0); 
using a protocol-defined characterization of diarrhea ( 2 watery/liquid stools/day), overall 
incidence was lower for APR and placebo (11.0 and 8.3). Serious AEs were lower with APR 
than placebo (2.8 vs 4.6). No opportunistic infections, reactivations of tuberculosis (TB), or 
cases of marked depression were seen. In general, no increase was seen in AE incidence/severity 
with longer-term exposure to APR up to 52 weeks. Apremilast was generally well tolerated.  
The long-term safety of apremilast, with or without concomitant csDMARDs, over 4 years was 
assessed in a pooled analysis of the Palace 1, 2, and 3 studies (Mease, 2017). Results from this 
analysis suggested a favorable and consistent safety profile over time. Importantly, the frequency 
of gastrointestinal AEs decreased with longer exposure to apremilast, and the frequency of other 
common AEs either decreased or remained stable with prolonged exposure (Table 10). The rates 
of infections did not increase over time, nor did the data indicate a need for specific laboratory 
monitoring. 
Treatment with apremilast was associated with an increase in adverse reactions of depression; 
0.3 (4/1441) of patients treated with apremilast discontinued treatment due to depression or 
depressed mood vs 0 placebo-treated patients (0/495). Depression was reported as serious in 
0.2 (3/1441) of patients exposed to apremilast vs 0 placebo-treated patients (0/495). Two 
patients who received placebo committed suicide vs 0 apremilast-treated patients. Importantly, 
the rates of depression remained low over time.  
 

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Table 10: 
Frequency of Common AEs Over 208 Weeks of Exposure 
APR-Exposure 
Period* 
Weeks  
0 to  52 
Weeks  
 52 to  104 
Weeks  
 104 to  156 
Weeks  
 156 to  208 
Subjects, n () 
APR30 
N721 
APR30 
n520 
APR30 
n443 
APR30 
n401 
 1 AE 
524 (72.7) 
316 (60.8) 
284 (64.1) 
234 (58.4) 
 1 SAE 
47(6.5) 
35 (6.7) 
40 (9.0) 
28 (7.0) 
AE leading to 
drug withdrawal 
56 (7.8) 
13 (2.5) 
7 (1.6) 
7 (1.7) 
Death 
0 (0.0) 
1
§ (0.2) 
0 (0.0) 
2
‡,║ (0.5) 
AEs in 5 of subjects, n () 
Diarrhea 
112 (15.5) 
20 (3.8) 
12 (2.7) 
4 (1.0) 
Nausea 
108 (15.0) 
11 (2.1) 
10 (2.3) 
3 (0.7) 
Headache 
75 (10.4) 
17 (3.3) 
12 (2.7) 
7 (1.7) 
Upper 
respiratory tract 
infection 
60 (8.3) 
27 (5.2) 
24 (5.4) 
21 (5.2) 
Nasopharyngitis 
41 (5.7) 
31 (6.0) 
20 (4.5) 
26 (6.5) 
APR30  apremilast 30 mg BID; AE  adverse event; n/m  number of subjects with 1 occurrence of the abnormality at any 
time point/number of subjects with 1 post-baseline value; ULN  upper limit of normal. 
Note: *Includes all subjects who received APR during the time interval relative to the start of APR treatment. §Motor vehicle 
accident on Day 489. ‡Cerebrovascular accident on Day 1,330 in a 69-year-old man, considered unrelated to study drug; subject 
had history of myocardial infarction, atrial fibrillation, and cerebrovascular accident. ║Stroke on Day 1,224 in a 58-year-old 
woman, considered unrelated to study drug; subject had a history of chronic ischemic heart disease, hypertension, alcoholism, 
and atrial fibrillation.  
 
Most AEs were mild or moderate in severity. Rates were very low for major cardiac events, 
malignant neoplasms, and serious opportunistic infections. It is noteworthy that systemic 
opportunistic infections did not occur with long-term exposure to apremilast. Marked laboratory 
abnormalities were infrequent, and most returned to baseline values with continued treatment. 
In a pooled analysis of Palace 1, 2, 3, and 4 (Celgene, 2017) for subjects receiving long-term 
treatment with APR 30 BID, the median (mean) weight change from baseline was -1.00 (-1.25) 
kg and -1.30 (-1.68) kg, respectively, at Week 52, and -1.00 (-1.70 kg) and -2.00 (-2.14) kg at 
Week 78. At the end of treatment, weight loss  53 was observed in 14.8 of subjects 
receiving apremilast 20 mg BID and 16.5 receiving apremilast 30 mg BID. Overall, no overt 
clinical consequences were seen with the weight loss observed with apremilast. 
The 5-year safety of apremilast was evaluated in a long-term analysis of the Palace 1 study 
(Kavanaugh, 2018). No new safety concerns were identified. For subjects entering the fifth year 
of apremilast 30 mg BID exposure, AEs occurring in 5 were upper respiratory tract infection, 

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nasopharyngitis, and urinary tract infection; most AEs were mild or moderate in severity. 
Apremilast 30 mg BID continued to demonstrate a favorable safety profile and was generally 
well tolerated. 
Please refer to the IB for detailed information concerning the available pharmacology, 
toxicology, drug metabolism, clinical studies, and adverse event profile of the investigational 
product (IP). 
1.3. 
Rationale 
1.3.1. 
Study Rationale and Purpose 
1.3.1.1. 
Unmet Medical Need  
Apremilast has been shown to be safe and efficacious in reducing signs and symptoms of PsA, as 
well as improving physical function (Cutolo, 2016; Edwards, 2016; Kavanaugh, 2014; 
Nash, 2018). Like most agents, the clinical development program of apremilast was restricted to 
subjects with 3 swollen and tender joints at baseline. This allowed for a limited proportion of 
subjects with asymmetric oligoarthritis at study entry. Consequently, the safety and efficacy of 
apremilast in patients with oligoarthritis remains to be further investigated.  
The current study is designed to evaluate the benefit: risk profile of apremilast in subjects with 
an early diagnosis of PsA ( 5 years since signs and symptoms began), presenting with 
oligoarthritis despite concurrent stable treatments with either NSAIDs and/or  1 csDMARD. 
1.3.1.2. 
Rationale for the Study Design 
Analyses in PsA subjects with oligoarthritis (defined by different combinations of limited 
numbers of swollen and tender joints) in five Phase 3 PsA studies (PSA-002, PSA-003, 
PSA-004, PSA-005 and PSA-006) indicated that in patients with oligoarticular PsA, apremilast 
30 mg BID was associated with a numerically greater proportion of subjects achieving the 
modified MDA (MDA-joint) at week 16 compared with placebo. In addition, results from the 
apremilast development program demonstrated that responses to apremilast improve over a 
period of up to 24 weeks when compared to placebo. Therefore, the 24-week, double-blind, 
placebo-controlled treatment period with frequent visits and assessments will provide adequate 
time to reasonably assess the onset of action of, and durability of, response to apremilast in 
achieving the modified MDA (MDA-Joints). The joints monitored for early escape must 
correspond to those affected at the Baseline Visit (sentinel joints). 
The Active-treatment Extension Phase (24 weeks) will allow for the investigation of the 
long-term efficacy, safety and tolerability of apremilast  concomitant therapies for the treatment 
of patients with oligoarthritis. In addition, this period will allow for the investigation of the 
impact of apremilast  concomitant therapies after a course of placebo  NSAIDs and/or 
 1 csDMARDs.  
1.3.1.3. 
Rationale for Dose, Schedule, and Regimen Selection  
The dosing regimen and dose of apremilast is based on the approved dosing regimen and dose of 
apremilast for the treatment of PsA.  

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After a dose titration over a 5-day period, an oral dose of apremilast 30 mg BID will be given to 
all subjects randomized or enrolled to receive apremilast. 
1.3.1.4. 
Rationale for Choice of Comparator Compounds  
The comparator of this study is Placebo. This will allow for the assessment of the risk / benefit of 
apremilast.  
To allow for the treatment of oligoarticular PsA, apremilast  NSAIDs and/or  1csDMARDs 
will be compared to placebo  NSAIDs and/or  1 csDMARDs. Stable low doses of 
glucocorticoids (prednisone  10 mg/day or equivalent) will be allowed. Indeed, it is understood 
that several patients with oligoarthritis are managed with NSAIDs and/or csDMARDs. 

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2. 
STUDY OBJECTIVES AND ENDPOINTS 
Table 11: 
Study Objectives 
Primary Objective 
 The primary objective of the study is to evaluate the efficacy of apremilast 
30 mg BID  NSAIDs and/or csDMARDs vs. Placebo  NSAIDs and/or 
csDMARDs in subjects with early oligoarticular psoriatic arthritis (PsA), 
assessed by modified MDA (MDA-Joints). 
Secondary Objective(s) 
 To evaluate the impact of treatment with apremilast 30 mg BID  NSAIDs 
and/or csDMARDs vs. Placebo  NSAIDs and/or csDMARDs on disease 
activity in subjects with early oligoarticular PsA. 
 To evaluate the impact of apremilast 30 mg BID  NSAIDs and/or 
csDMARDs vs. Placebo  NSAIDs and/or csDMARDs on patient-reported 
outcomes (PROs) in subjects with early oligoarticular PsA. 
 To evaluate the safety and tolerability of apremilast 30 mg BID  NSAIDs 
and/or csDMARDs vs. Placebo  NSAIDs and/or csDMARDs in subjects 
with early oligoarticular PsA.  
Exploratory Objective(s) 
The exploratory objectives are: 
 csDMARDs  Conventional synthetic disease-modifying antirheumatic drugs; cDAPSA  Clinical 
disease activity in psoriatic arthritis (without measuring C-reactive protein); 
NSAIDs 
 Nonsteroidal anti-inflammatory drugs; MDA  Minimal disease activity; HAQ-DI  Health Assessment Questionnaire 
Disability Index; PGA  Physician’s Global Assessment of Disease activity; PRO  Patient-reported outcome; 
PsAID  Psoriatic Arthritis Impact of Disease (questionnaire). 
 

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Table 12: 
Study Endpoints 
Endpoint 
Name 
Description 
Timeframe 
Efficacy Endpoints at Week 16: Double-Blind Placebo-Controlled Treatment Phase 
Primary 
MDA-Joints 
Proportion of subjects who achieve a clinical state of minimal disease activity 
defined MDA-Joints. Subjects must achieve  1 SJC and TJC, plus 3 out of 5 
of the remaining cut-off values (BSA  3; Patient pain (VAS)  15; Patient 
global disease activity (VAS)  20; HAQ0.5; Tender entheseal points  1 
(based on Leeds Enthesitis Index - LEI).  
Week 16 
Secondary  
 
cDAPSA remission or low 
disease activity 
Proportion of subjects who achieve remission (defined by clinical disease 
activity in psoriatic arthritis [DAPSA]  4 score) or low disease activity 
(defined by cDAPSA  4 but  13 score). 
Week 16 
Swollen Joint Count (SJC)  1  Proportion of subjects with SJC  1.  
Week 16 
Tender Joint Count (TJC)  1  
Proportion of subjects with TJC  1.  
Week 16 
Patient's global assessment of 
disease activity  
Proportion of subjects whose global assessment of disease activity score  20 
in the visual analogue scale (VAS).  
Week 16 
Patient's assessment of pain 
Proportion of subjects whose assessment of pain score  15 in VAS. 
Week 16 
PsAID-12 
Change from Baseline in the Psoriatic Arthritis Impact of Disease 12-item for 
clinical trials (PsAID-12) questionnaire.  
Week 16 
PASDAS good and moderate 
response 
Proportion of patients achieving a good or moderate response in PASDAS 
score.  
Week 16 
 
 

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Table 12: 
Study Endpoints (Continued) 
Endpoint 
Name 
Description 
Timeframe 
Exploratory Efficacy Endpoints: Evaluated for the Duration of the Study: 
(Double-Blind Placebo-Controlled Treatment Phase and/or the Active-treatment Phase) 
Exploratory 

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Table 12: 
Study Endpoints (Continued) 
Endpoint 
Name 
Description 
Timeframe 
Exploratory Efficacy Endpoints: Evaluated for the Duration of the Study: 
(Double-Blind Placebo-Controlled Treatment Phase and/or the Active-treatment Phase) 
Exploratory 
(Continued) 

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Table 12: 
Study Endpoints (Continued) 
Endpoint 
Name 
Description 
Timeframe 
Exploratory Efficacy Endpoints: Evaluated for the Duration of the Study: 
(Double-Blind Placebo-Controlled Treatment Phase and/or the Active-treatment Phase) 
Exploratory 
(Continued) 
 

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Table 12: 
Study Endpoints (Continued) 
Endpoint 
Name 
Description 
Timeframe 
Exploratory 
(Continued) 
Safety 
Endpoints 
Safety Endpoints: Evaluated throughout the duration of the study: 
Adverse events 
Type, frequency, severity, and relationship of adverse events (AEs) to investigational 
product (IP). 
Throughout the duration of 
the study 
Discontinuation due to 
AEs 
Number of subjects who discontinue IP due to any AE. 
Throughout the duration of 
the study 
Clinically significant 
changes in physical 
examination, vital 
signs, and/or laboratory 
findings 
Frequency of clinically significant changes in physical examination, vital signs, 
and/or laboratory findings. 
Throughout the duration of 
the study 
 

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3. 
OVERALL STUDY DESIGN  
3.1. 
Study Design 
The study will be conducted in compliance with the International Council for Harmonisation 
(ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good 
Clinical Practice (GCP) and applicable regulatory requirements. 
This is a Phase 4, multicenter, randomized, double-blind, placebo-controlled, parallel-group 
study to evaluate the efficacy, safety and tolerability of apremilast (CC-10004) in subjects with 
early ( 5 years since signs and symptoms began) oligoarticular PsA (according to 
Classification Criteria for Psoriatic Arthritis [CASPAR] criteria) despite treatment with 
either NSAIDs and/or  2 csDMARD.  Subjects must also meet the following criteria:  1 SJ but 
 4 SJ, and  1 TJ but  4 TJ at the Screening Visit and confirmed prior to randomization at the 
Baseline Visit. 
Given that this is a phase 4 study, all subjects are required to meet the existing apremilast 
regulatory labeling conditions specific to the countries where enrollment will take place (eg, 
Food and Drug Administration [FDA], European Medicines Agency [EMA], Health Canada]. 
There is no planned protocol extension following the end of the study.  
Approximately 285 subjects will be randomized in a 2:1 ratio to either apremilast 30 mg BID or 
identically appearing placebo, with approximately 
 subjects assigned to the active treatment 
group and approximately 
 subjects assigned to receive placebo. Treatment assignment will be 
stratified via an Interactive Web Response System (IWRS) based on concomitant use of 
glucocorticosteroids at baseline (yes/no) and prior/concomitant use of a csDMARD, either MTX 
or SSZ (ie, csDMARD-naïve; csDMARD use prior to baseline [treatment not continued]; or 
csDMARD use prior to and concomitant at baseline). The number of subjects who are 
csDMARD-naïve is targeted to comprise up to 50  of the subjects enrolled in the study. 
This is a 56-week study. Subjects will have up to 4 weeks in the Screening Phase, followed by 
24 weeks in the Double-blind, Placebo-controlled Treatment Phase, which provides an 
opportunity for “early escape” at Week 16, allowing subjects to receive treatment with 
apremilast 30 mg BID beginning at Week 16. At the Week 24 Visit, all subjects will be offered 
entry into the Active-treatment Extension Phase. Subjects enrolled in the Extension Phase will 
receive treatment with apremilast (30 mg BID) until the end of the study (ie, up to the Week 48 
Visit) or until early discontinuation.  
Beginning at the Week 28 Visit, all subjects in the Extension Phase will be dispensed open-label 
apremilast (30 mg BID) in high-density polyethylene (HDPE) bottles (Section 7.3). Subjects, 
Investigators and persons responsible for the ongoing conduct of the study will continue to be 
blinded to the original treatment assignment. Subjects must be clearly instructed to follow dosing 
instructions. Subjects may discontinue at any time during the study.  
After all subjects complete the Week 24 Visit (or discontinue prematurely from the study), 
selected members of the Amgen study team who do not have direct interaction with subjects will 
be unblinded for the analysis of the Week 24 data. These persons may include but are not limited 

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to the following: Therapeutic Area Head, Study Lead, Medical Director and the Statistician. The 
results from these analyses may be published prior to the end of the study. 
Subjects, Investigators and persons responsible for the ongoing conduct of the study will 
continue to be blinded to the original treatment assignment until the end of the study. These 
persons are those individuals that have direct interaction with subjects and/or subject 
assessments, and may include but are not limited to the following: Clinical Trial Manager, Data 
Manager, Clinical Research Associates (Amgen and External Partners) and Site Monitors.  
This is a 56-week study which will consist of 4 phases:  
 Screening Phase – up to 4 weeks 
 Randomized, Double-blind, Placebo-controlled Treatment Phase – Weeks 0 to 24. 
Henceforth, this will be referred to as the Placebo-controlled Phase.  
o Subjects will be randomly assigned in a 2:1 ratio to either apremilast 30 mg BID 
or placebo.  Subjects randomized to apremilast will be dose-titrated in a blinded 
fashion.  
o Dose titration is described in Study Treatments, Section 7.2. and Section 7.3. 
o Subjects with no improvement in SJC (sentinel joints) at Week 16 are eligible for 
early escape, at the discretion of the Investigator and will receive apremilast 
30 mg BID. The joints monitored for early escape must be the “sentinel joints” 
(ie, the joints affected at baseline). 
o Placebo-treated subjects who escape early will be transitioned to apremilast 
30 mg BID in a blinded fashion via an Interactive Web Response System (IWRS), 
while apremilast-treated subjects will remain on the original treatment assigned at 
baseline. Placebo-treated subjects will be dose-titrated in a blinded fashion. 
o All subjects who complete this 24-week treatment phase will have the option to 
enter the Active-treatment Extension Phase.  
 Active-treatment Extension Phase – Week 24 to Week 48. Henceforth, this will be 
referred to as the Extension Phase.  
o All subjects will receive apremilast 30 mg BID until the completion of the study 
(ie, up to the Week 48 Visit). All remaining placebo-treated subjects will be 
dose-titrated in a blinded fashion. 
o Beginning at the Week 28 Visit, all subjects in the Extension Phase will be 
dispensed open-label apremilast (30 mg BID) as described in Study Treatments 
and Section 7.3. 
 Post-treatment Observational Follow-up Phase – up to 4 weeks. Henceforth this will be 
referred to as the Observational Follow-up Phase.  
o All subjects who complete the Placebo-controlled Phase or the Extension Phase or 
discontinue early will participate in the 4-week Observational Follow-up Phase.  
o The Observational Follow-up visit should be performed 4 weeks after the last 
dose of IP ( 7 days). 

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Figure 1: Overall Study Design 
 
 
* – Subjects with no improvement in SJC (sentinel joints) at Week 16 are eligible for early escape, at the discretion of the Investigator. 
 
Abbreviations: BID  twice daily; csDMARD  conventional synthetic disease-modifying antirheumatic drug; MDA  Minimal Disease Activity; NSAIDs  
non-steroidal anti-inflammatory drug. 

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3.2. 
Study Duration for Subjects  
Subjects who complete the study will spend up to a total of 56 weeks in this study: 
 Up to 4 weeks in the Screening Phase 
 Weeks 0 to 24 (ie, 24 weeks) in the Placebo-controlled Phase 
 Weeks 24 to 48 (ie, 24 weeks) in the Extension Phase  
 Weeks 48 to 52 (ie, 4 weeks) in the Observational Follow-up Phase 
3.3. 
End of Trial  
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up, or the date of receipt of the last data point from the last subject that is 
required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, 
whichever is the later date. 
Study completion is defined as the date of the last visit of the last subject in this clinical study. 
Study completion for an individual subject is defined as reaching 48 weeks of treatment and 
completion of the Observational Follow-up Visit (Week 52), 4 weeks after the last dose of IP 
( 7 days). A subject not meeting this definition is considered an early discontinuation subject 
(Section 6.2.1). For the purpose of analysis, study completion for an individual subject is defined 
as reaching the Week 48 Visit.  

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4. 
STUDY POPULATION 
4.1. 
Number of Subjects  
Approximately 285 subjects will be enrolled worldwide.  
4.2. 
Inclusion Criteria 
Subjects must satisfy the following criteria to be enrolled in the study: 
1. Subject is a male or female,  18 years at time of consent. 
2. Subjects must understand and voluntarily sign an informed consent document prior to any 
study related assessments/procedures being conducted. 
3. Subject is willing and able to adhere to the study visit schedule and other protocol 
requirements. 
4. Subject must have signs and symptoms of PsA  5 years duration at the time of the 
Screening Visit. 
5. Subject meets the CASPAR (Appendix B) criteria for PsA at the Screening Visit. 
6. Subject must have a total number of swollen joints greater than 1 and equal or less than 4 
( 1 but  4 swollen joints) at the Screening Visit and confirmed prior to randomization at 
the Baseline Visit. 
7. Subject must have a total number of tender joints greater than 1 and equal or less than 4 ( 1 
but  4 tender joints) at Screening and confirmed prior to randomization at the Baseline Visit. 
8. Subjects taking oral glucocorticosteroids must be on a stable dose of prednisone  10 mg/day 
or equivalent for at least 4 weeks prior to the Baseline Visit (Section 8.1). 
9. For all regions, the local Regulatory Label for treatment with apremilast must be followed. 
For example, subjects in the EU must have had inadequate response or intolerance to a prior 
csDMARD.  
10. Subjects taking 1 protocol-allowed csDMARD (methotrexate [MTX] or sulfasalazine [SSZ]) 
to treat PsA may enter the study provided that the treatment is taken at a stable dose for at 
least 3 months prior to the Baseline Visit. See Permitted Medications (Section 8.1) for details 
describing dose criteria.  
11. Subjects exposed to MTX or SSZ and stopped treatment due to intolerance or due to safety 
reasons may enter the study provided that treatment was stopped within at least 4 days of the 
Baseline Visit. 
12. Subjects taking NSAIDs may enter the study provided that the dose is stable for at least 
2 weeks prior to the Baseline Visit. Subjects may discontinue NSAIDs at any time up to and 
including the Baseline Visit, prior to study randomization. 
13. Females of childbearing potential (FCBP)† must have a negative pregnancy test at Screening 
and the Baseline Visit. While on investigational product and for at least 28 days after taking 
the last dose of investigational product, FCBP who engage in activity in which conception is 
possible must use one of the approved contraceptive§ options described below: 

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Option 1: Any one of the following highly 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 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. 
NOTE: Option 2 may not be acceptable as a highly effective contraception option in all countries 
per local guidelines/regulations. 
 
† A female of childbearing potential 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). 
14. Must be in general good health (except for psoriatic arthritis) 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). 
 
4.3. 
Exclusion Criteria 
The presence of any of the following will exclude a subject from enrollment: 
1. Prior use of  2 csDMARD to treat PsA. 
2. Prior exposure to a JAK-inhibitor, including tyk2 inhibitors and/or a biologic DMARD. 
3. Use of intra-articular (IA) or intra-muscular (IM) glucocorticoid injection within 8 weeks 
before the Baseline Visit. 
4. Use of leflunomide within 12 weeks of randomization. Subjects who stopped leflunomide 
and completed 11 days of treatment with cholestyramine (8 g, 3 x daily) prior to the 
Baseline Visit may enter the study. 
5. Prior use of cyclosporine.  
6. Prior treatment with apremilast, or participation in a clinical study, involving apremilast. 
7. Use of any investigational drug within 4 weeks of the Baseline Visit, or 5 
pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer). 
8. History of clinically significant or uncontrolled disease (as determined by the 
Investigator), which places the subject at unacceptable risk if he/she were to participate in 
the study. 

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9. Any condition, including the presence of laboratory abnormalities, which places the 
subject at unacceptable risk if he/she were to participate in the study. Subjects with a 
creatinine clearance level less than 30 mL/min (estimated by the Cockcroft–Gault 
equation) will be considered to have severe renal impairment and will be excluded from 
the study. 
10. 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. 
11. Pregnant or breast feeding. 
12. Active substance abuse or a history of substance abuse within 6 months prior to 
Screening. 
13. History of allergy or hypersensitivity to any component of the investigational product. 
14. History of positive human immunodeficiency virus (HIV), or congenital or acquired 
immunodeficiency (eg, Common Variable Immunodeficiency Disease). 
15. Active tuberculosis or a history of incompletely treated tuberculosis. 
16. Bacterial infections requiring treatment with oral or injectable antibiotics, or significant 
viral or fungal infections, within 1 week of Screening. Any treatment for such infections 
must have been completed and the infection cured, at least 1 week prior to Screening and 
no new or recurrent infections prior to the Baseline Visit. 
17. 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.  
18. Major surgery (including joint surgery) within 8 weeks prior to the Screening Visit or 
planned major surgery within 6 months following the Baseline Visit. 
19. Rheumatic autoimmune disease other than PsA, including, but not limited to: systemic 
lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, 
polymyositis, or fibromyalgia. 
20. Prior history of or current inflammatory joint disease other than PsA (eg, gout, reactive 
arthritis, rheumatoid arthritis [RA], ankylosing spondylitis, Lyme disease), which 
confounds the ability to interpret data from the study. 
21. Erythrodermic, guttate, or generalized pustular psoriasis at randomization. 
 

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5. 
TABLE OF EVENTS 
Table 13: 
Table of Events 
 
Screening 
Placebo-controlled Phase 
 
Extension Phase 
 
Early 
Termination 
Visit 
Observational 
Follow-up- 
Phase 
Visit Number 
1 
Screening 
2 
Baseline 
3 
4 
5 
6 
7 
8 
9 
Early 
Termination 
10 
Week (Visit Window) 
-28 Days 
Week 0  
4 
(3 days) 
12 
( 3 days) 
16a 
(3 days) 
24b 
(3 days) 
28c 
(3 days) 
40 
( 1 week) 
48 
(1 week)) 
ETd 
Obs. Follow-up 
Visite 
4 wks after the 
last dose of IP 
( 7 days) 
Informed consent 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Demographics 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Medical History/PsA 
History 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Smoking and alcohol intake 
history 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Inclusion/Exclusion Criteria 
X 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Prior/Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Prior/Concomitant 
Procedures 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety and Laboratory 
Assessments  
 
 
 
 
 
 
 
 
 
 
 
Vital Signs f 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Height 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
 
Weight g 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
Diarrhea assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
- 

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Table 13: 
Table of Events (Continued) 
 
Screening 
Placebo-controlled Phase 
Extension Phase 
Early 
Termination 
Visit 
Observational 
Follow-up- 
Phase 
Visit Number 
1 
Screening 
2 
Baseline 
3 
4 
5 
6 
7 
8 
9 
Early 
Termination 
10 
Week (Visit Window) 
-28 Days 
Week 0  
4 
(3 days) 
12 
( 3 days) 
16a 
(3 days) 
24b 
(3 days) 
28c 
(3 days) 
40 
( 1 week) 
48 
(1 week)) 
ETd 
Obs. Follow-up 
Visite 
4 wks after the 
last dose of IP 
( 7 days) 
Complete Physical 
Examination 
X 
- 
- 
- 
- 
X 
- 
- 
X 
X 
- 
Limited Physical 
Examination 
- 
X 
X 
X 
X 
- 
X 
X 
- 
- 
- 
Laboratory Evaluations 
(including high sensitivity 
C-reactive protein and 
urinalysis)  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
- 
Rheumatoid Factor 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Pregnancy Test for Females 
of Child Bearing Potential 
(FCBP) and Contraception 
Education h 
X 
X 
- 
- 
- 
- 
- 
- 
X 
X 
- 
Adverse Events i 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Efficacy 
Assessment 
 
 
 
 
 
 
 
 
 
 
 
Tender Joint Count (0-68) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
- 
Swollen Joint Count (0-66) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
- 
Physician’s Global 
Assessment of  
Disease Activity (VAS) 
- 
X 
X 
X 
X 
X 
X 
X 
X 
X 
- 
Patient’s Global Assessment 
 of Disease Activity (VAS) 
- 
X 
X 
X 
X 
X 
X 
X 
X 
X 
- 

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Table 13: 
Table of Events (Continued) 
 
Screening 
Placebo-controlled Phase 
Extension Phase 
Early 
Termination 
Visit 
Observational 
Follow-up- 
Phase 
Visit Number 
1 
Screening 
2 
Baseline 
3 
4 
5 
6 
7 
8 
9 
Early 
Termination 
10 
Week (Visit Window) 
-28 Days 
Week 0  
4 
(3 days) 
12 
( 3 days) 
16a 
(3 days) 
24b 
(3 days) 
28c 
(3 days) 
40 
( 1 week) 
48 
(1 week)) 
ETd 
Obs. Follow-up 
Visite 
4 wks after the 
last dose of IP 
( 7 days) 
Patient’s Assessment of Pain 
(VAS) 
- 
X 
X 
X 
X 
X 
X 
X 
X 
X 
- 
Dactylitis 
 j 
X 
Enthesitis assessment-
 LEI 
- 
X 
X 
X 
X 
X 
X 
X 
X 
X 
- 
HAQ-DI 
- 
X 
X 
X 
X 
X 
X 
X 
X 
X 
- 
BSA 
- 
X 
X 
X 
X 
X 
X 
X 
X 
X 
- 
PROs/QOLs 
 
 
 
 
 
 
 
 
 
 
 
PsAID-12 
X 

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Table 13: 
Table of Events (Continued) 
 
Screening 
Placebo-controlled Phase 
Extension Phase 
Early 
Termination 
Visit 
Observational 
Follow-up- 
Phase 
Visit Number 
1 
Screening 
2 
Baseline 
3 
4 
5 
6 
7 
8 
9 
Early 
Termination 
10 
Week (Visit Window) 
-28 Days 
Week 0  
4 
(3 days) 
12 
( 3 days) 
16a 
(3 days) 
24b 
(3 days) 
28c 
(3 days) 
40 
( 1 week) 
48 
(1 week)) 
ETd 
Obs. Follow-up 
Visite 
4 wks after the 
last dose of IP 
( 7 days) 
Health Economics Assessment 
 
 
 
 
 
 
 
 
 
 
 
Dosing 
 
 
 
 
 
 
 
 
 
 
 
Dispense Study Drug 
- 
X 
X 
X 
X 
X 
X 
X 
- 
- 
- 
Return/Count Study Drug 
- 
- 
X 
X 
X 
X 
X 
X 
X 
X 
- 
BID  twice daily; BSA  Body Surface Area;
 FCBP  Females of Child Bearing Potential; HAQ-DI  Health Assessment 
Questionnaire – Disability Index; IP  Investigational Product;
LEI  Leeds Enthesitis Index;
Obs. 
Follow-up Visit  Observational Follow-up Visit; PROs  Patient Reported Outcomes; PsAID  PsA Impact of Disease;
 
 QOL  Quality of Life;
VAS  Visual 
Analog Scale;
 
a At the Week 16 Visit, subjects with no improvement in SJC (sentinel joints) at Week 16 are eligible for early escape, at the discretion of the Investigator and will receive 
treatment with apremilast 30 mg BID. The joints monitored for early escape must correspond to those affected at the Baseline Visit (sentinel joints).  
b All subjects who complete the Week 24 Visit will enter Extension Phase and receive apremilast 30 mg BID. The original treatment assignments (apremilast 30 mg BID or 
placebo) will remain blinded until the end of the study. 
c Beginning at the Week 28 Visit, all subjects in the Extension Phase will be dispensed open-label apremilast (30 mg BID) in high-density polyethylene (HDPE) bottles. Subjects 
must be clearly instructed to follow dosing instructions.  
d Subjects who discontinue the study prior to the Week 48 Visit, will have an Early Termination (ET). 
 
 
e The Observational Follow-up Visit will be conducted 4 weeks after the last dose of IP (± 7 days). 
f If an on site study visit is replaced with a telemedicine assessment, vital signs will not be measured. 
g If an on site study visit is replaced with a telemedicine assessment, the subject’s weight will not be measured. 
h Females of childbearing potential (FCBP) will have a serum pregnancy test done at the Screening Visit and at the Week 48 Visit (or Early Termination Visit). The urine 
pregnancy test collected at the Baseline Visit must be assessed prior to study randomization. The Investigator must educate all FCBP about the options for and correct use of 
contraceptive methods at the Screening and Baseline Visits and at any time when a subject’s contraceptive measures or ability to become pregnant change. An unscheduled 
pregnancy test should be administered if the subject has missed a menstrual period or at the discretion of the Investigator per country specific guidelines. 

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i Details pertaining to the monitoring and collection of adverse events are included in Section 10. Information about specific safety assessments are provided in Section 6.5. 
j For the dactylitis assessment at Screening, only a binary evaluation is needed (yes/no). 
 

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6. 
PROCEDURES 
The following procedures will be conducted as outlined in Table 13, the Table of Events. 
6.1. 
Screening Period 
Following the signing of the informed consent form (ICF), screening evaluations will be 
performed for all subjects to determine study eligibility. These evaluations must be completed 
within 28 days of first dosing unless noted otherwise below.  
Waivers to the protocol will not be granted during the conduct of this trial, under any 
circumstances. 
Safety laboratory analyses and all assessments will be performed centrally. Screening laboratory 
values must demonstrate subject eligibility, but may be repeated within the screening window, if 
necessary. 
The following evaluations will be performed at the frequency specified in Table 13, Table of 
Events: 
 Demographics include year of birth, sex, race, and ethnicity-if allowed by local 
regulations, will be collected. 
 Smoking and alcohol intake history 
 Complete medical history including all relevant medical conditions diagnosed, and 
occurring prior to the Screening Visit, should also be recorded. 
 PsA history will be collected. 
 Prior and concomitant medication evaluation including all medications (prescription and 
nonprescription, including vitamins) taken by the subject up to  28 days prior to the 
Screening Visit should be recorded.  All medications taken by the subject at any time 
during the study must also be recorded. Other key medications and therapies, such as 
previous treatment for tuberculosis or relevant diseases, should also be recorded. 
 Prior and concomitant PsA-related medications: 
o All medications for PsA and oligoarthritis taken by the subject are to be recorded 
in the subject’s source document prior to study randomization. 
o Careful attention must be taken when randomizing a subject in IWRS regarding a 
subject’s use of glucocorticosteroids and DMARDs. This includes use prior to 
study randomization and at the time of study randomization at the Baseline Visit. 
o PsA medications and all other medications must also be recorded in the eCRF 
according to the CRF guidelines.  
o Contraindicated PsA medications: 
▪ For this protocol, contraindication to PsA medications will refer to those 
subjects who have a pre-existing medical condition where administration 
of the medication is not possible since the treatment could cause harm to 

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the subject, resulting in the subject NOT TAKING the medication. For 
subjects who meet this criterion, this information must be recorded in the 
source document along with the pre-existing medical condition that 
prevented the subject from receiving the treatment. The pre-existing 
medical condition must also be reported the eCRF. 
 Prior and concomitant procedures including all procedures occurring  28 days before the 
Screening Visit must be collected. 
 Vital signs 
 Height and weight 
 Chest X-ray is not required per protocol but may be done at the discretion of the 
Investigator or according to local regulations and guidelines. 
 Diarrhea assessment (Section 6.5.5)  
 Complete physical examination (recorded in the source document) 
 Laboratory evaluations will be performed by a central laboratory and are described in 
Section 6.5.7 and are listed below: 
o Hematology panel   
o Chemistry panel 
o Urinalysis 
▪ Microscopic urinalysis (epithelial cells, red blood cells [RBCs], white 
blood cells [WBCs], crystals, bacteria, and casts) will be performed only if 
the urinalysis is abnormal. 
o High sensitivity C-reactive Protein (hsCRP) 
o Rheumatoid factor 
 Adverse event evaluation (continuously) 
 SJC and TJC assessment 
 Pregnancy test is required for all female subjects of childbearing potential.  Serum beta 
human chorionic gonadotropin -hCG pregnancy test will be performed at the Screening 
Visit. Urine pregnancy test will be performed to assess subject eligibility within 72 hours 
prior to the first administration of IP (negative results required for dispensing IP). 
 Contraception education will be performed by the Investigator at screening for all FCBP 
about the options for and correct use of contraceptive methods at the Screening and 
Baseline Visits and at any time when a FCBP’s contraceptive measures or ability to 
become pregnant changes. 
o A pregnancy test should be performed if the FCBP subject has missed a menstrual 
period or the contraception method has changed 
o Counseling about pregnancy precautions and the potential risks of fetal exposure 
must be conducted.  

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6.2. 
Treatment Period  
The Treatment Period includes the Placebo-controlled Phase and the Extensions Phase. 
The subject will begin treatment upon confirmation of eligibility. The subject must start 
treatment within 28 days of signing the ICF.  The following evaluations will be performed at the 
frequency specified in Table 13. In addition, at the discretion of the investigator, an Unscheduled 
Visit may be performed to evaluate subject safety and efficacy as needed. 
 Concomitant medications evaluation 
 Concomitant procedures evaluation 
 Limited or complete physical examination (source documented only) as described in 
Table 13. During the Extension Phase, limited physical exam may be done at the 
discretion of the Investigator. 
 Vital signs 
 Diarrhea assessment (Section 6.5.5)  
 Weight (Section 6.5.2) 
 Hematology panel  
 Chemistry panel 
 hsCRP 
 Urinalysis 
 Microscopic urinalysis (epithelial cells, RBCs, WBCs, crystals, bacteria, and 
casts) will be performed only if the urinalysis is abnormal. 
 Adverse event evaluation (continuously) 
 Efficacy assessments (see Section 6.4) 
 Patient reported outcomes (PROs), Quality of Life (QOL) assessments and Health 
Economics (Section 6.6) 
 Urine pregnancy testing will be done for FCBP prior to dosing at the Baseline Visit. 
Serum beta human chorionic gonadotropin -hCG pregnancy test will be performed at 
the Week 48 Visit 
 IP dispensing and accountability 
6.2.1. 
End of Treatment 
An end of treatment (EOT) evaluation will be performed for subjects who are withdrawn from 
treatment for any reason, as soon as possible, after the decision to permanently discontinue 
treatment has been made.  

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The following evaluations will be performed as specified in Table 13, Table of Events: 
 Complete physical examination (source documented only) 
 Vital signs 
 Weight 
 Diarrhea assessment (Section 6.5.5) 
 Concomitant medications evaluation 
 Concomitant procedures evaluation 
 Subject reported outcomes or quality of life 
 Adverse event evaluation  
 Hematology panel 
 Chemistry panel 
 hsCRP 
 Urinalysis  
 Microscopic urinalysis (epithelial cells RBCs, WBCs, crystals, bacteria, and 
casts) will be performed only if the urinalysis is abnormal. 
 Serum beta human chorionic gonadotropin -hCG pregnancy test will be performed for 
FCBP. 
 Counseling about pregnancy precautions and the potential risks of fetal exposure must be 
conducted.  
 Efficacy Assessments (Section 6.4) 
 PROs (Quality of Life (QOL) assessments and Health Economics (Section 6.6) 
 Return/count of study drug  
6.3. 
Observational Follow-up 
6.3.1. 
Safety Follow-up 
All subjects will be followed for 28 days after the last dose of apremilast for AE reporting, as 
well as SAEs made known to the Investigator at any time following the protocol-required 
reporting period or after end of study , as described in Section 10. 
The following evaluations will be performed at the Observational Follow-up Visit, or if 
necessary via telephone contact, as specified in Table 13, Table of Events: 
 Concomitant medications evaluation 
 Concomitant procedures evaluation 

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 Adverse event (non-serious and serious) evaluation 
6.4. 
Efficacy Assessments 
The following assessments will be conducted as outlined in Table 13, Table of Events. Subject 
questionnaires and clinician assessments will be reported using electronic data capture. These 
data will be entered directly into the ERT tablet. 
6.4.1. 
Modified Minimal Disease Activity–Joints (MDA-Joints) and its Components  
For this study, the MDA-Joints (Appendix C) is used as the primary endpoint and is defined as 
Tender Joint Counts (TJC)  1 and Swollen Joint Counts (SJC)  1 plus 3 of any of the 5 criteria: 
1) patient’s global VAS on a 100-mm scale  20, 2) patient pain VAS on a 100-mm scale  15, 
3) physical function [HAQ-DI]  0.5, 4) enthesitis count  1 (based on the Leeds Enthesitis 
Index) and 5) psoriasis Body Surface Area (BSA)  3.  Joint assessment to be based on 66 
swollen joints and 68 tender joints (see Section 6.4.1.1). Assessment of the joint counts will be 
performed by the evaluator, however, calculation of the MDA-Joints will be done 
programmatically. 
6.4.1.1. 
Joint Assessment 
A modified joint count that includes the distal interphalangeal joints of the fingers and toes (the 
“68 tender and 66 swollen” joint scores; (Appendix D) will be performed at every visit. Joint 
tenderness and swelling will be noted as “present” or “absent,” with no quantitation of severity. 
In case of digit(s) with dactylitis, each joint of the affected digit must be evaluated for tenderness 
and swelling.  
Joints that are swollen or tender should be marked with a “tick”. In the event that a joint is 
injected with intra-articular or intra-muscular glucocorticoid (allowed only after Week 24 
assessments are completed, and up to the Week 48 Visit), this joint should be marked by an “X” 
and won’t be assessed if the study visit occurs within 4 weeks (28 days) of the intra-articular 
(IA) injection. In order to maintain consistency throughout the study, the same evaluator should 
perform the joint assessments for a given subject at a study site at each study visit. 
6.4.1.2. 
Patient’s Global Assessments of Disease Activity 
The Patient’s (Subject’s) Global Assessments of Disease Activity (Appendix E) is an assessment 
of how active a subject’s psoriatic arthritis was on average during the last week. The subject will 
be asked to place a vertical line on a visual analogue scale (VAS) on which the left-hand 
boundary represents the lowest level of disease activity and the right-hand boundary represents 
the highest. Distance from the mark to the left-hand boundary will be recorded in millimeters, 
except when calculating cDAPSA score, where the distance will be calculated in centimeters. 
6.4.1.3. 
Patient’s Pain Visual Analogue Scale  
The pain visual analogue scale (VAS) is the subject’s assessment of how much pain he/she had, 
on average, last week in his/her joints due to PsA.  The subject will be asked to place a vertical 
line on a VAS on which the left-hand boundary represents “no pain,” and the right-hand 
boundary represents “pain as severe as can be imagined” (Appendix E). The distance from the 

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mark to the left-hand boundary will be recorded in millimeters, except when calculating 
cDAPSA score, where the distance will be calculated in centimeters. 
6.4.1.4. 
HAQ-DI 
The HAQ-DI (Appendix F; Fries, 1980) is a 20-question, self-administered instrument that 
measures the subject’s functional ability on a 4-level difficulty scale (0 to 3, with 0 representing 
normal or no difficulty; and 3 representing an inability to perform). Eight categories of 
functioning are included: dressing, rising, eating, walking, hygiene, reach, grip, and usual 
activities (Bruce, 2003). This scale is sensitive to change and is a good predictor of future 
disability (Aletaha, 2006). 
6.4.1.5. 
Enthesitis: Leeds Enthesitis Index 
In the evaluation of MDA-Joints, enthesitis will be assessed by the Leeds Enthesitis Index (LEI) 
(Appendix G; Healy, 2008). 
For the LEI, pain will be assessed at the following entheses (tendon insertions): Lateral 
epicondyle humerus (left/right (L/R)); Medial condyle femur (L/R); Achilles tendon insertion 
into calcaneum (L/R). The LEI ranges from 0 to 6. 
6.4.1.6. 
BSA 
BSA (Appendix H) is a measurement of involved skin. The overall BSA affected by psoriasis is 
estimated based on the palm area of the subject’s hand (entire palmar surface or “handprint”), 
which equates to approximately 1 of total body surface area. All subjects will have their BSA 
assessed by the Evaluator.  
6.4.1.7. 
Physician’s Global Assessments of Disease Activity  
The Physician’s (Evaluator’s) Global Assessments of Disease Activity is an assessment of how 
active a subject’s psoriatic arthritis was on average during the last week. For the Physician’s 
(Evaluator’s) Global Assessments of Disease Activity, evaluator should mark a single vertical 
mark on a 100-mm VAS (see Appendix E), with zero representing the lowest level of disease 
activity or pain and 100 representing the highest. The distance from the mark to the left-hand 
boundary of the scale will be recorded in millimeters (Appendix E, Felson, 1995). 
6.4.2. 
Enthesitis: 
 
In addition to assessment by the Leeds Enthesitis Index (Section 6.4.1.5), enthesitis will also be 
assessed using the 
 

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6.4.3. 
Dactylitis 
Dactylitis assessment will be done at screening, only a binary evaluation is needed (yes/no). 
 
6.4.4. 
Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) 
The cDAPSA score (Appendix K) is based on the numerical summation of 4 disease activity 
variables: tender and swollen joints, patient global and pain assessments on a 10 cm Visual 
Analogue Scale (VAS) (Appendix E). Proposed cut-offs for cDAPSA are a score  4 for 
remission, a score  4 and  13 for low disease activity,  13 and  27 for moderate disease 
activity, and  27 for high disease activity. Evaluation of components of cDAPSA is described 
above. The calculation of the cDAPSA will be performed programmatically. 
6.4.5. 
Psoriatic Arthritis Disease Activity Score (PASDAS) 
The PASDAS (Helliwell, 2014; Appendix L) is a weighted index comprising assessments of 
joints, function, acute-phase response, quality of life (QOL), and patient and physician by VAS. 
The calculation of the PASDAS will be performed programmatically using the formula below: 
PASDAS  ((0.18 x Physician global VAS)  (0.159 x Patient global VAS) – (0.253 x 
SF36 – PCS)  (0.101 x LN (Swollen joint count  1))  (0.048 x LN (Tender joint count  
1))  (0.23 x LN (Leeds Enthesitis Count  1))  (0.377 x LN (Dactylitis count  1))  (0.102 
x LN (CRP  1)) 2)*1.5. 
Note: LN  natural logarithm, PCS  physical component summary scale of SF36, CRP  C-
reactive protein in mg/l, SF36  Medical Outcomes Study Short Form-36. All VAS scores 
are 0–100 mm. Swollen joint count is 66 joints, and tender joint count 68. The score range of 
the PASDAS is 0–10, with worse disease activity represented by higher scores. Definition of 
good or moderate response is detailed in Appendix L. 
6.4.6. 
High sensitivity C-reactive Protein 
High sensitivity C-reactive protein (hsCRP) and rheumatoid factor will be performed at a central 
laboratory along with the other clinical laboratory assessments described in Section 6.5.7. 

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6.5. 
Safety Assessments 
In addition to daily safety monitoring conducted by Investigators and individual study personnel, 
AEs, serious adverse events (SAEs), discontinuations and laboratory findings will be reviewed 
by the study team. The review follows the Council for International Organizations for Medical 
Sciences, Working Group VI (CIOMS VI) recommendations.  
The study will be conducted in compliance with the ICH of Technical Requirements for 
Registration of Pharmaceuticals for Human Use/GCP and applicable regulatory requirements. 
The following assessments will be conducted as outlined in Table 13, Table of Events. 
6.5.1. 
Serum and Urine Pregnancy Tests for Females of Childbearing Potential  
A serum pregnancy test with a sensitivity of  15 mIU/mL will be required for FCBP subjects at 
Screening and the Week 48 Visit (or at the Early Termination Visit for subjects who prematurely 
discontinue from the study). Urine pregnancy test will be performed on all FCBP subjects at the 
Baseline Visit, prior to randomization. A urine pregnancy test kit will be provided by the central 
laboratory. Pregnancy tests should be performed if the FCBP subject has missed a menstrual 
period or the contraception method has changed. 
In addition to the assessments specified in Table 13, the Investigator will follow country 
guidelines regarding the monitoring of pregnancy testing at any scheduled or unscheduled visit 
and will document the test result in the source document.  At the discretion of the Investigator, a 
serum pregnancy may be done. 
6.5.2. 
Vital Signs, Height and Weight  
Vital signs, including temperature, pulse, and seated blood pressure, will be taken during the 
visits indicated in Table 13, Table of Events. Height will be measured and recorded at Screening; 
weight will also be measured and recorded at every visit. 
In the event of unexplained and clinically significant weight loss, subjects should be evaluated and 
discontinuation of study treatment should be considered by the Investigator. 
6.5.3. 
Complete/Limited Physical Examination 
A complete physical examination includes evaluations of skin, nasal cavities, eyes, ears, lymph 
nodes, and respiratory, cardiovascular, gastrointestinal, neurological, and musculoskeletal 
(assessment of joints and spine) systems. A complete physical examination is done at Screening 
and other designated visits as indicated in Table 13, Table of Events. A limited physical 
examination includes evaluations of skin, lymph nodes, and respiratory, cardiovascular, and 

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musculoskeletal systems. A limited physical examination is done at the Baseline Visit and other 
designated visits as indicated in Table 13. 
6.5.4. 
Psychiatric Evaluation 
Treatment with apremilast is associated with an increase in adverse reactions of depression. 
Before using apremilast in subjects with a history of depression and/or suicidal thoughts or 
behavior, the Investigator should carefully weigh the risks and benefits of treatment with 
apremilast in such patients. Subjects should be advised of the need to be alert for the emergence 
or worsening of depression, suicidal thoughts or other mood changes, and if such changes occur 
to contact the Investigator.  
If a subject suffers from new or worsening psychiatric symptoms, or if suicidal ideation or 
suicidal attempt is identified, it is recommended to discontinue the subject participation to the 
study (see Section 11). 
6.5.5. 
Diarrhea, Nausea and Vomiting 
Apremilast has been associated with AE reports of diarrhea in clinical trials. Most diarrhea 
events were of mild or moderate severity and reported within the first 2 weeks of treatment, 
usually resolving within 4 weeks without medical intervention. 
Diarrhea is the passage of three or more loose or liquid stools per day, or more frequently than is 
normal for the individual (World Health Organization [WHO], 2013). Following the definition of 
diarrhea by the WHO and taking a more conservative approach, the AE of diarrhea in this 
protocol is defined as having two or more watery/liquid stools in a day.  
To better characterize diarrhea and to distinguish similar events coding to the Medical Dictionary 
of Regulatory Activities (MedDRA) preferred term of diarrhea, subjects reporting diarrhea or 
similar events (eg, frequent bowel movements, loose bowels, etc.) will be asked whether they 
have had two or more watery/liquid stools in a day. Subjects who respond “yes” to this question 
will be further asked how often, on average, have they experienced two or more watery/liquid 
stools in a day. Subjects who respond “no” to the question will not be asked any further 
questions. This data will be reported via electronic data capture in the ERT tablet. If an AE is 
identified by the Investigator, the AE and respective attributes will be reported in the clinical 
database. If the AE meets serious criteria, it must be reported to Amgen Global Patient Safety 
(see Section 10.5). 
There have been post-marketing reports of severe diarrhea, nausea, and vomiting associated with 
the use of apremilast. Most events occurred within the first few weeks of treatment.  In some 
cases, patients were hospitalized. 
Subjects 65 years of age or older and subjects taking medications that can lead to volume 
depletion or hypotension may be at a higher risk of complications. Subjects should be monitored 
for the occurrence of severe diarrhea, nausea and vomiting.  If a subject develops severe 
diarrhea, nausea and vomiting, discontinuation of study treatment may be necessary (see 
Section 11). 

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6.5.6. 
Tuberculosis 
After an extensive clinical development program, there is no current evidence that apremilast has 
the potential to activate latent TB. Therefore, no TB testing will be done in this protocol. 
Investigators can test for TB if clinically indicated, using the site’s local or country-specific 
guidelines. If the subject has active or latent TB, he/she should be treated according to local 
guidelines. Subjects who require TB treatment at any time during the study must be 
discontinued.  
6.5.7. 
Clinical Laboratory Evaluations 
Clinical laboratory evaluations will be performed by the central laboratory as indicated in 
Table 13, Table of Events. These include complete blood count (red blood cell [RBC] count, 
hemoglobin, hematocrit, white blood cell [WBC] count and differential, absolute WBC counts, 
platelet count) and serum chemistries (total protein, albumin, calcium, phosphorous, glucose, 
triglycerides, total cholesterol [TC], total bilirubin, alkaline phosphatase, aspartate 
aminotransferase [AST; serum glutamic-oxaloacetic transaminase, SGOT], alanine 
aminotransferase [ALT; serum glutamic pyruvic transaminase, SGPT], sodium, potassium, 
chloride, bicarbonate [carbon dioxide, CO2], blood urea nitrogen, creatinine, creatinine clearance 
[estimated by the Cockcroft–Gault equation], lactate dehydrogenase [LDH], and magnesium); 
rheumatoid factor; high-sensitivity C-reactive protein (hsCRP), 
urinalysis (specific gravity, pH, glucose, ketones, protein, blood, bilirubin, leukocyte esterase, 
nitrite, and urobilinogen. Microscopic urinalysis (epithelial cells, red blood cells [RBCs], white 
blood cells [WBCs], crystals, bacteria, and casts) will be performed only if the urinalysis is 
abnormal. 
6.5.8. 
Adverse Events 
All subjects will be monitored for adverse events (AEs) during the study. Assessments may 
include monitoring of any or all of the following parameters: the subject’s clinical symptoms, 
laboratory, pathological, radiological, or surgical findings; physical examination findings; or 
other appropriate tests and procedures. 
All AEs will be recorded by the Investigator from the time the subject signs informed consent to 
28 days after the last dose of IP. Adverse events and serious adverse events (SAEs) will be 
recorded on the AE page of the electronic case report form (eCRF), the paper SAE reporting 
form (SAEs) and in the subject’s source documents. All SAEs must be reported to Amgen 
Global Patient Safety immediately (ie, within 24 hours of the Investigator’s knowledge of the 
event) by recording on the CRF and completing the paper SAE Report Form which is sent 
directly to Amgen Global Patient Safety by facsimile or email. 
Details of AE reporting can be found in Section 10 of the protocol. It should be noted that 
worsening of a subject’s psoriatic arthritis should be considered as worsening of disease under 
study and should not be captured as an adverse event. 
 
6.6. 
Patient Reported Outcomes or Quality of Life or Health Economics 
Questionnaires will be performed and as indicated in Table 13, Table of Events. 

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6.6.1. 
The PsA Impact of Disease 12-Item (PsAID-12) Questionnaire 
The PsAID-12 Questionnaire (Appendix N; Gossec, 2014) is a 12-item, self-administered 
questionnaire that reflects the impact of PsA from the perspective of the patient. It is composed 
of 12 physical and psychological domains. Each domain is rated from 0 to 10 with a different 
weighting. The total score is divided by 20. The final score has a range from 0 (best status) to 10 
(worst status) with a cut-off  4.  

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7. 
DESCRIPTION OF STUDY TREATMENTS 
7.1. 
Description of Investigational Product(s) 
The chemical name of apremilast (CC-10004) is N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-
(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl] acetamide.   
Apremilast and placebo will be provided as identically appearing by the Sponsor and labeled 
appropriately as investigational product for this study. In addition, tablets (both apremilast and 
placebo) required for dose titration cards will also be provided. 
Please refer to the IB for more details on approved indications, known precautions, warnings, 
and adverse reactions of apremilast. 
The apremilast dosing schedule to be followed for this study is described in Section 7.2.  
Additional information may be included on the label as needed or applicable. Label(s) for IP will 
contain information as required per local health authority. 
7.2. 
Treatment Administration and Schedule 
Tablets will be taken by mouth twice daily, in the morning (AM) and in the evening (PM), 
approximately 12 hours apart, with no food restrictions. To mitigate potential gastrointestinal 
(GI) adverse events, dose titration shall be implemented over a 5-day period (see Table 14). 
At the Week 0 (ie, initial randomization), Week 16 (ie, for Early Escape subjects), and Week 24 
(ie, Active-treatment Phase) visits, subjects will be dispensed blister cards with 10, 20, and 
30 mg apremilast tablets or identically appearing placebo for the dose titration. Subjects will be 
dispensed blister cards containing 30 mg apremilast tablets or identically appearing placebo at 
designated visits (Table 13). Beginning at the Week 28 Visit, subjects will be dispensed open 
label bottles with 30 mg apremilast tablets. Pictures of the blister card configurations are shown 
in Appendix T. Dose modifications are not permissible in this study. Apremilast and placebo 
tablets (oral IP) are identical in appearance. 
 

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Table 14: 
Treatment of Schema for Dose Titration at Baseline 
Dose 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Group 
AM 
PM 
AM 
PM 
AM 
PM 
AM 
PM 
AM 
PM 
Placebo 
(dummy 
titration) 
10 mg 
placebo 
 20 mg 
placebo 
 30 mg 
placebo 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
placebo 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
placebo 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
placebo 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
placebo 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
placebo 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
placebo 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
placebo 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
placebo 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
placebo 
30 mg 
apremilast 
(titration) 
10 mg 
apremilast  
20 mg 
placebo 
 30 mg 
placebo 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
placebo 
10 mg 
apremilast  
20 mg placebo 
 30 mg 
placebo 
10 mg 
apremilast  
20 mg placebo 
 30 mg 
placebo 
10 mg 
apremilast 
 20 mg 
placebo 
 30 mg 
placebo 
10 mg placebo 
 20 mg 
apremilast  
30 mg placebo 
10 mg placebo 
 20 mg 
apremilast  
30 mg placebo 
10 mg placebo 
 20 mg 
apremilast  
30 mg placebo 
10 mg placebo 
 20 mg 
apremilast  
30 mg placebo 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
apremilast 
 
 
Table 15: 
Treatment Schema for Dose Titration at Week 16 (Early Escape) or Week 24 
Dose 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Group 
AM 
PM 
AM 
PM 
AM 
PM 
AM 
PM 
AM 
PM 
Placebo to 
30 mg 
apremilast 
(titration) 
10 mg 
apremilast  
20 mg 
placebo 
 30 mg 
placebo 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
placebo 
10 mg 
apremilast  
20 mg placebo 
 30 mg 
placebo 
10 mg 
apremilast  
20 mg placebo 
 30 mg 
placebo 
10 mg 
apremilast 
 20 mg 
placebo 
 30 mg 
placebo 
10 mg placebo 
 20 mg 
apremilast  
30 mg placebo 
10 mg placebo 
 20 mg 
apremilast  
30 mg placebo 
10 mg placebo 
 20 mg 
apremilast  
30 mg placebo 
10 mg placebo 
 20 mg 
apremilast  
30 mg placebo 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
apremilast 
30 mg 
apremilast 
(dummy 
titration)  
10 mg 
placebo 
 20 mg 
placebo 
 30 mg 
apremilast 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
apremilast 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
apremilast 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
apremilast 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
apremilast 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
apremilast 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
apremilast 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
apremilast 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
apremilast 
10 mg placebo 
 20 mg 
placebo 
 30 mg 
apremilast 
 
 

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7.3. 
Method of Treatment Assignment 
After the informed consent is signed, subjects will be assigned a subject identification number 
using a centralized interactive web response system (IWRS). At the Baseline Visit, a centralized 
schema will be applied to assign subjects who meet the inclusion and none of the exclusion 
criteria in a 2:1 ratio to receive either apremilast 30 mg tablets or placebo. The IWRS will 
stratify the randomized subjects by their use of glucocorticosteroids (yes/no) and use of a 
csDMARD: (csDMARD-naïve; csDMARD use prior to baseline; or csDMARD use prior to and 
concomitant at baseline). 
Subjects who are randomized to apremilast at baseline will be dose-titrated during their first 
week of active treatment (see Section 7.2), while subjects who are randomized to placebo will 
receive identically appearing placebo titration cards while continuing to receive their assigned 
dose of placebo BID.  
Subjects with no improvement in the swollen joint count at Week 16 are eligible for early 
escape. The joints monitored for early escape must correspond to those affected at baseline 
(sentinel joints). To maintain the study blind, placebo-treated subjects who escape early will be 
transitioned in a blinded fashion via an IWRS to apremilast 30 mg BID and apremilast-treated 
subjects will remain blinded on their original treatment assignment. Placebo subjects will be 
dose-titrated during their first week of active treatment (see Section 7.2), while subjects who 
were already on apremilast 30 mg BID will receive identically appearing placebo titration cards 
while continuing to receive their assigned dose of apremilast 30 mg BID.  
At the Week 24 Visit, subjects will be offered to enter a 24-week Active - treatment Extension 
Phase (Extension Phase). All subjects enrolled in the Extension Phase will receive treatment with 
apremilast (30 mg BID) until the completion of the study (ie, up to the Week 48 Visit) or until 
early discontinuation. Placebo subjects will be dose titrated (5-day titration period). All subjects 
will receive treatment cards of identical appearance to maintain the blinding of the original 
treatment assignments (apremilast 30 mg BID or placebo). 
Beginning at the Week 28 Visit, the next scheduled study visit following the placebo titration 
period, all subjects in the Extension Phase will be dispensed open-label apremilast (30 mg BID) 
in high-density polyethylene (HDPE) bottles. Subjects must be clearly instructed to follow 
dosing instructions. 
Designated study personnel at the investigational sites will be assigned password protected, 
coded identification numbers, which give them authorization to log into the IWRS to randomize 
subjects. The system will present a menu of questions by which the study personnel will identify 
the subject and confirm eligibility. When all questions have been answered, the IWRS will 
assign a randomization identification number. Confirmation of the randomization will be sent via 
fax to the investigational site, Amgen and/or its representative. 
During the study visits, the pharmacy or authorized study personnel at the investigational site 
will dispense coded IP kits in accordance with the randomization number assigned by the IWRS.  
7.4. 
Packaging and Labeling 
The label(s) for IP will include Sponsor name, address and telephone number, the protocol 
number, IP name, dosage form and strength (where applicable), amount of IP per container, lot 

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number, expiry date (where applicable), medication identification/kit number, dosing 
instructions, storage conditions, and required caution statements and/or regulatory statements as 
applicable. Additional information may be included on the label as applicable per local 
regulations. 
All IP, including placebo and apremilast tablets, will be supplied by Amgen Inc. to the principal 
Investigator as blister cards during the Placebo-controlled Phase. 
Starting at the Week 28 Visit, apremilast 30 mg tablets will be supplied in HDPE bottles with 
child-resistant caps. 
7.5. 
Investigational Product Accountability and Disposal  
The Investigator, or designee, is responsible for taking an inventory of each shipment of oral IP 
received, and comparing it with the accompanying IP shipping order/packing list.  
The Investigator(s) or designee(s) will verify the accuracy of the information on the form, sign 
and date it, retain a copy in the study file, and record the information in the IRT. 
Investigational product will be stored per the storage conditions identified on drug label. At the 
study site, all IP will be stored in a locked, safe area to prevent unauthorized access. 
Amgen (or designee) will review with the Investigator and relevant site personnel the process for 
investigational product return, disposal and/or destruction including responsibilities for the site 
versus Amgen (or designee). 
7.6. 
Study Medication Dispensing and Counting 
After the subject has satisfied all inclusion and exclusion criteria, study medication will be 
dispensed as specified in Table 13, Table of Events. The tear-off label from each blister card 
should be pasted into the drug accountability document in each subject’s record. Subjects must 
be instructed to return all previously issued empty blister card(s), empty study drug bottle(s) 
and/or unused study medication at the time that new medication is issued. A detailed record of 
tablets issued and returned at each visit must be maintained in the subject’s record. 
Amgen (or designee) will review with the Investigator and relevant site personnel the process for 
investigational product return, disposal, and/or destruction including responsibilities for the site 
versus Amgen (or designee). 
7.7. 
Investigational Product Compliance 
Study personnel will review the instructions printed on the package with the study subjects prior 
to dispensing the IP. Investigational Product will be dispensed as noted in Table 13, Table of 
Events. The subjects will be instructed to return the IP containers, including any unused 
medication, to the study site at each visit for tablet counts and reconciliation. Subjects will be 
asked whether they have taken their IP as instructed at each study visit. Any problems with IP 
compliance will be reviewed with the subject. If subject misses 4 or more consecutive days of 
dosing, Amgen must be contacted to decide whether dosing should resume or whether the 
subject should be terminated from the Treatment Phase of the study and enter the Observational 
Follow-up Phase. 

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Gross compliance problems (eg, missing 4 or more consecutive days of dosing or taking less 
than 75 of the doses between study visits) should be discussed with Amgen. Compliance is 
defined as taking between 75 and 120 of dispensed IP. 
7.8. 
Overdose 
Overdose, as defined for this protocol, applies to protocol-required dosing of the investigational 
product(s) (IPs) only. Therefore, for a drug to be subject to the overdose definition it must be 
both required and an investigational drug. In this study the only required and investigational 
drug is apremilast and the control arm drug (ie, placebo), hence overdose definition will apply to 
only apremilast (or matching placebo). Other required or optional non-study drugs intended for 
prophylaxis of certain side effects, etc, are excluded from this definition. 
Overdose for this protocol, on a per dose basis, is defined as ingestion of 4 or more 30 mg 
apremilast (or matching placebo) tablets in any 24-hour period, whether by accident or 
intentionally. On a schedule or frequency basis, an overdose is defined as dosing more than 
4 times during any 24-hour period.  
Adverse Events associated with an overdose must be collected on the Adverse Events page of the 
eCRF (see Section 10) for all overdosed subjects, but the overdose itself is not considered an AE. 
If the AE associated with the overdose meets seriousness criteria, it must also be reported to 
Amgen Global Patient Safety using the paper SAE report form (see Section 10.5). 

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8. 
CONCOMITANT MEDICATIONS AND PROCEDURES 
All medications (prescription and non-prescription), treatments and therapies taken by the 
subject from screening throughout their entire participation in the study, including those initiated 
prior to the start of the study, must be recorded on the subject’s source document and on the 
appropriate page of the eCRF. The dose, unit, frequency, route, indication, the date the 
medication was started and the date the medication was stopped (if not ongoing) must be 
recorded. Subjects may continue receiving standard of care therapy (eg, folic acid for those on 
MTX) if not explicitly prohibited as per protocol. Additional instructions can be found in the 
electronic Case Report Form (eCRF) Completion Guidelines.  
8.1. 
Permitted Concomitant Medications and Procedures 
The following concomitant medications and procedures are permitted during the study:  
 Oral glucocorticosteroids are to be taken on a stable dose up to the Week 24 Visit: 
o Prednisone  10 mg/day (or prednisolone equivalent) for at least 4 weeks prior to 
the Baseline Visit must be continued and maintained through the Week 24 Visit 
(change in dose and/or discontinuation are not allowed except for safety reasons 
or for lack of availability). 
 NSAIDs (and/or narcotic analgesics) are allowed during the study, provided that the 
NSAIDs are taken on a stable dose for at least 2 weeks prior to the Baseline Visit. 
o The stable dose of NSAIDs or narcotic analgesics must be continued and 
maintained from the Baseline Visit through the Week 24 Visit. Change in doses, 
increase or decrease, and/or discontinuation of NSAIDs or narcotic analgesics 
will not be allowed except for safety reasons or for lack of availability. After the 
Week 24 Visit, the dose of NSAIDs or narcotic analgesics may be adjusted as 
clinically required. 
o NSAIDs or narcotic analgesics that are administered on an as needed basis (PRN) 
should be recorded on the Prior/Concomitant Medications page of the eCRF.  
 csDMARDs –  
o Only 1 csDMARD (MTX or SSZ) for the treatment of PsA is permitted during the 
first 24 weeks of the study, provided that the treatment is taken on a stable dose 
 3 months prior to the Baseline Visit.  
o Subjects exposed to MTX or SSZ and stopped treatment due to intolerance or due 
to safety reasons may enter the study provided that treatment was stopped within 
at least 4 days of the Baseline Visit  
 The allowed dose for permitted csDMARDs are: MTX (oral or parenteral) 
 25 mg /week; SSZ (oral)  3 gm/daily 
 Low-dose aspirin (acetylsalicylic acid, up to 325 mg per day) for cardiovascular 
prophylaxis.  
 Loperamide and antidiarrheal drugs with antisecretory effect (eg, racecadotril). 

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 A nonmedicated skin emollient (eg, Eucerin cream) for body psoriasis lesions only.  
After the Week 24 Visit, changes in the following therapy will be permitted as clinically required 
for subjects with worsening arthritic symptoms of PsA: 
 Change of NSAID type and/or dose 
 Parenteral glucocorticoids are allowed, provided that the following criteria are met: 
o Administration of no more than 40 mg intra-articular (IA) or intra-muscular (IM) 
glucocorticosteroid (triamcinolone hexacetonide or equivalent) injection at a single 
visit.  
o Injected joints should not be counted during the visits that will take place within 4 
weeks of the intra-articular injection. Joints should be marked with an X. 
o Intra-articular injection should not be performed after week 44 visit (ie, 4 weeks 
prior to study end). 
 Oral glucocorticosteroids may be adjusted as clinically required 
o Short course ( 2 weeks) of oral corticosteroids, including a Medrol Dosepak, not to 
exceed one course in any 6-month interval  
 Non-biologic DMARDs: methotrexate ( 25 mg/week), sulfasalazine ( 3 gm/day), 
leflunomide ( 20 mg/day), hydroxychloroquine ( 400 mg/day), chloroquine 
( 600 mg/day). 
After Week 24, if subjects experience a decrease in PsA clinical disease activity, the Investigator 
may opt to taper the background treatment; however, only one agent may be reduced or tapered 
at any one time. After the first agent has been tapered (not required to be zero), the dose must be 
stable for at least 4 weeks prior to tapering the next agent. Subjects are recommended to have a 
reduction of background therapy in the following order (when applicable): First csDMARD, 
second glucocorticosteroids and third NSAIDs or other pain medication. If clinically indicated, 
the Investigator may opt to reduce the medications in a different order. Any further 
questions/concerns regarding dose reductions can be discussed with the Sponsor.  
In order to minimize the impact on ongoing efficacy assessments, the investigator should use the 
least intensive regimen to ameliorate the subject’s worsening PsA symptoms. 
8.2. 
Concomitant Medications Not Recommended 
It has been observed that coadministration with strong cytochrome P450 3A4 (CYP3A4) enzyme 
inducers, rifampicin, resulted in a reduction of systemic exposure of apremilast, which may 
result in a loss of efficacy of apremilast. Therefore, the use of strong CYP3A4 enzyme inducers 
(eg, rifampicin, phenobarbital, carbamazepine, phenytoin and St. John’s Wort) with study 
treatment is not recommended. 
8.3. 
Prohibited Concomitant Medications and Procedures 
The following concomitant medications and concomitant procedures are prohibited during the 
study as noted below: 

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 Use of 1 csDMARD prior to Week 24 
 Prior use of tofacitinib or any other JAK-inhibitor 
 Use of any biologic DMARD.   
 Use of leflunomide within 12 weeks of randomization. Subjects who stopped 
leflunomide and completed 11 days of treatment with cholestyramine (8 g TID) prior 
to the Baseline Visit may enter the study. Leflunomide may be initiated 
( 20 mg/day) after Week 24. 
 Prior use of cyclosporine  
 Use of DMARDs other than MTX or SSZ for the treatment of PsA, except for MTX 
( 25 mg/week), or SSZ ( 3 gm daily), prior to Week 24. 
 Use of intra-articular (IA) and intra-muscular (IM) glucocorticoid injection within 
8 weeks before the Baseline Visit. Use of IA and IM injections may be administered 
after Week 24 as discussed in Section 8.1. 
8.4. 
Required Concomitant Medications and Procedures 
There are no required concomitant medications or procedures. 
 

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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Overview  
The primary efficacy analysis of the proportion of subjects achieving the modified MDA 
(MDA-Joints) at Week 16 and the secondary analyses will be performed after all subjects 
complete the placebo-controlled period (Week 0 to 24) or terminate early prior to Week 24 visit. 
Additional analyses will be performed after the final database lock when all subjects complete 
the study or terminate early. This section outlines the statistical analysis strategy for the data 
collected in the study. A detailed Statistical Analysis Plan (SAP), including data handling and 
imputation rules, will be prepared and finalized before unblinding of the treatment assignment 
for the 24-week, placebo-controlled, double-blind treatment phase of the study or any analysis 
procedures are conducted, whichever is earlier.  
9.2. 
Study Population Definitions 
The Full Analysis Set (FAS) will consist of all subjects who are randomized. Efficacy analyses 
will be primarily based on the FAS and subjects will be included in the treatment group to which 
they are randomized. 
The Per Protocol (PP) population will consist of all subjects who receive at least one dose of 
study medication and have no major protocol violations during the 24-week placebo-controlled 
treatment period. The final determination of major protocol violations will be made prior to the 
unblinding of treatment assignment and will be documented. The PP analyses will be based on 
the PP population and subjects will be included in the treatment group for the treatment they 
actually receive. 
The Safety population will consist of all subjects who receive at least one dose of study 
medication. The safety analyses will be based on the safety population and subjects will be 
included in the treatment group for the treatment they actually receive. 
9.3. 
Sample Size and Power Considerations 
Sample size estimation was based on the results from integrated analyses of subpopulation data 
from five Phase 3 studies (PSA-002, PSA-003, PSA-004, PSA-005, and PSA-006). Assuming a 
15 dropout rate during the randomized, placebo-controlled, double-blind treatment phase, a 
sample size of approximately 
 for the Apremilast 30 mg BID and placebo groups, 
respectively, will have 80 power to detect a true 15 difference (30 versus 15) in the 
proportions of subjects achieving the modified MDA (MDA-Joints) between the Apremilast 
30 mg BID and placebo groups, using a chi-square test with a two-sided significance level of 
0.05.  
9.4. 
Background and Demographic Characteristics 
Subjects’ age, weight, height and other continuous demographic and baseline characteristics will 
be summarized using descriptive statistics (mean, standard deviation, minimum and maximum), 
while gender, race, and other categorical variables will be summarized with frequency 
tabulations. Medical history data will be summarized using frequency tabulations. Treatment 

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history (including oral glucocorticosteroid, NSAIDs, and csDMARD use) will be summarized 
using frequency distributions.  
9.5. 
Subject Disposition 
Subject disposition (counting of analysis populations; and subjects enrolled, randomized, and 
completing or discontinuing in the study, along with primary reason for discontinuation) will be 
summarized using frequency and percent by study phase. A summary of subjects enrolled by site 
will be provided. Protocol deviations will be summarized using frequency tabulations. 
9.6. 
Efficacy Analysis 
9.6.1. 
Efficacy Evaluation for the Placebo-Controlled, Double-Blind Treatment Phase 
The analyses of efficacy endpoints will be primarily based on the FAS. In addition, supportive 
analyses using the Per Protocol population will also be conducted for the primary endpoint.  
Efficacy results will be considered statistically significant after consideration of the control of 
multiplicity, as specified in Section 9.6.2. Two-sided p-values and confidence intervals (CIs) will 
be reported, and all statistical tests will be conducted at the significance level of 0.05. 
9.6.2. 
Multiplicity 
Statistical tests for comparing the apremilast 30 mg BID and placebo will be conducted for the 
primary endpoint and the secondary efficacy endpoints as listed in Section 2. 
The multiplicity of the analyses performed for the primary and selected secondary efficacy 
endpoints will be adjusted using a sequential test procedure to preserve the family-wise type I 
error rate. The hierarchy order of the selected secondary endpoints to be followed in the 
sequential test procedure will be specified in the statistical analysis plan (SAP). 
It should be noted that the above multiplicity control will only be conducted for the primary 
endpoint and the key secondary endpoints that are evaluated in the randomized, placebo-
controlled, double-blind treatment phase. 
9.6.3. 
Primary Efficacy Endpoint 
The primary efficacy endpoint, proportion of subjects who achieve the modified MDA 
(MDA-Joints) at Week 16, between the Apremilast 30 mg BID and placebo groups will be 
compared using a Cochran-Mantel-Haenszel test, controlling for concomitant use of 
glucocorticosteroids at baseline (yes/no) and use of a csDMARD: (csDMARD-naïve; csDMARD 
use prior to baseline; or csDMARD use prior to and concomitant at baseline). 
Subjects who have discontinued prior to Week 16 due to lack of efficacy or adverse event will be 
treated as non-responders in the analysis; and the multiple imputation methodology will be 
utilized to impute the data for subjects whose modified MDA at Week 16 is missing for a reason 
other than lack of efficacy or adverse event. Sensitivity analyses will be performed using the 
non-responder imputation for subjects who have discontinued prior to Week 16, or do not have 
sufficient information for a definitive determination of the modified MDA (MDA-Joints) status 
at Week 16.  

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9.6.4. 
Secondary Endpoints 
For the secondary endpoints, the analyses of binary responses in the placebo-controlled phase 
will be similar to the analysis of the primary endpoint. That is, a Cochran-Mantel-Haenszel test 
adjusted for concomitant use of glucocorticosteroids at baseline (yes/no) and use of a 
csDMARD: (csDMARD-naïve; csDMARD use prior to baseline; or csDMARD use prior to and 
concomitant at baseline) will be used to compare the response rates between the apremilast 
30 mg BID and the placebo groups.  
A mixed-effect model of repeated measures (MMRM) will be used to analyze the continuous 
endpoints. The MMRM model will use change from baseline as the dependent variable and 
include treatment group, time, treatment-by-time interaction, use of glucocorticosteroids (yes/no) 
and use of a csDMARD (csDMARD-naïve; csDMARD use prior to baseline; or csDMARD use 
prior to and concomitant at baseline) as factors, and baseline value as a covariate. Time will be 
treated as a categorical variable in the MMRM model.  
All analyses on endpoints including joint counts will be performed on those joints that are 
affected at baseline (defined as sentinel joints). 
 
 
9.6.5. 
Active-Treatment Phase.  
Efficacy endpoints beyond Week 24 will be summarized using descriptive statistics for 
continuous variables and frequency tabulation for discrete variables.  
9.7. 
Safety Analysis 
The safety analyses will be performed using the safety population as defined in Section 9.2. 
Adverse events will be classified using the Medical Dictionary for Drug Regulatory Activities 
(MedDRA) classification system. All adverse events will be summarized by system organ class 
and preferred term; in addition, by severity and relationship to investigational product separately. 
Adverse events leading to death, if any, or to discontinuation from treatment, serious adverse 
events, and study drug-related adverse events will be summarized separately. A subject having 
the same event more than once will be counted only once using the maximum severity. 
Laboratory data will be summarized by visit descriptively (mean, standard deviation, median, 
minimum, and maximum). Number and percentage of subjects with marked laboratory 
abnormalities will be provided. In addition, shift tables showing the number of subjects with 
values low, normal, and high based on the normal ranges pretreatment versus post treatment will 
be provided.  
Vital sign measurements, including weight, will be summarized by visit descriptively. In 
addition, shift tables showing the number of subjects with values low, normal, and high based on 
the normal reference ranges pretreatment versus post treatment will be provided. 
To account for the exposure to the study medication, the exposure adjusted incidence rate will 
also be calculated for adverse events and marked laboratory abnormalities, as appropriate.  
9.8. 
Interim Analysis 
Not applicable. 

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9.9. 
Other Topics 
9.9.1. 
Investigational Product Compliance (Tablets) 
Investigational product record information will be summarized. Overall compliance will be 
estimated by the proportion of subjects who take between 75 and 120 of the intended 
quantity of IP. 
9.9.2. 
Concomitant Therapy 
All concomitant treatments documented during the study period will be summarized in frequency 
tabulations. The Anatomical Therapeutic Chemical coding scheme of the World Health 
Organization (WHO) will be used to group medications into relevant categories for these 
tabulations. Separate data summaries of background medications will be provided. 

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10. 
ADVERSE EVENTS 
10.1. 
Monitoring, Recording and Reporting of Adverse Events 
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen 
in a subject during the course of a study. It may be a new intercurrent illness, a worsening 
concomitant illness, an injury, or any concomitant impairment of the subject’s health, including 
laboratory test values (as specified by the criteria in Section 10.3), regardless of etiology. Any 
worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre-
existing condition) should be considered an AE. A diagnosis or syndrome should be recorded on 
the AE/SAE page of the CRF rather than the individual signs or symptoms of the diagnosis or 
syndrome. 
Abuse, withdrawal, sensitivity or toxicity to an investigational product should be reported as an 
AE.  Overdose, accidental or intentional, whether or not it is associated with an AE should be 
reported on the overdose CRF.  (See Section 7.8 for the definition of overdose.)  Any sequela of 
an accidental or intentional overdose of an investigational product which meets the definition of 
an adverse event, should be reported as an AE on the CRF.  If the sequela of an overdose meets 
serious criteria, then it must be marked as serious on the CRF, and the paper SAE Report 
form.   The overdose itself should not be reported as an AE. 
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for apremilast overdose. 
Actual treatment should depend on the severity of the clinical situation and the judgment and 
experience of the treating physician. 
All subjects will be monitored for AEs during the study. Assessments may include monitoring of 
any or all of the following parameters: the subject’s clinical symptoms, laboratory, pathological, 
radiological or surgical findings, physical examination findings, or findings from other tests 
and/or procedures. 
All AEs will be recorded by the Investigator from the time the subject signs informed consent 
until 28 days after the last dose of IP as well as any SAEs made known to the Investigator at any 
time following the protocol-required reporting period or after end of study will also be reported 
for these subjects. All adverse events (serious/non-serious) will be recorded on the CRF, the 
paper SAE Report form (SAEs) and in the subject’s source documents.  All SAEs must be 
reported to Amgen Global Patient Safety within 24 hours of the Investigator’s knowledge of the 
event by recording on the CRF and completing the paper SAE Report Form which is sent to 
Amgen Global Patient Safety by facsimile/email. 
10.1.1. 
Monitoring, Recording and Reporting AEs of Diarrhea 
The PDE4 inhibitors, including apremilast, have been associated with AE reports of diarrhea. To 
better characterize and understand all reported AEs of diarrhea, further information will be 
collected. Please refer to Section 10.2 for further details on how to record such AEs. 
10.2. 
Evaluation of Adverse Events 
A qualified Investigator will evaluate all adverse events as to:  

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10.2.1. 
Seriousness  
An SAE is any AE occurring at any dose that: 
 Results in death; 
 Is life-threatening (ie, in the opinion of the Investigator, the subject is at immediate 
risk of death from the AE); 
 Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay); 
 Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions); 
 Is a congenital anomaly/birth defect; 
 Constitutes an important medical event. 
Important medical events are defined as those occurrences that may not be immediately life-
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above. 
Medical and scientific judgment should be exercised in deciding whether such an AE should be 
considered serious. 
Events not considered to be SAEs are hospitalizations for: 
 A standard procedure for protocol therapy administration. However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE.  
 Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition. 
 The administration of blood or platelet transfusion as routine treatment of studied 
indication. However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE. 
 A procedure for protocol/disease-related investigations (eg, surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling). However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
remains a reportable SAE. 
 Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE. 
 A procedure that is planned (ie, planned prior to start of treatment on study); must be 
documented in the source document and the CRF. Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE. 
 An elective treatment of or an elective procedure for a pre-existing condition, 
unrelated to the studied indication, that has not worsened from baseline.  
 Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above. 

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If an AE is considered serious the AE page of the CRF and the paper SAE Report Form must be 
completed. All SAEs must be reported to Amgen Global Patient Safety within 24 hours of the 
Investigator’s knowledge by submitting the paper SAE report form via facsimile/email directly 
to Amgen Global Patient Safety. 
For each AE, the Investigator will provide information on severity, start and stop dates, 
relationship to the IP, action taken regarding the IP, and outcome. 
10.2.2. 
Severity/Intensity 
For each AE, the Investigator must assess the severity/ intensity of the event.  
Mild 
 Asymptomatic or mild symptoms; clinical or diagnostic observations only. 
 Intervention not indicated. 
 Activities of daily life (ADLs) minimally or not affected. 
 No or minimal intervention/therapy may be required.  
Moderate  
 Symptom(s) cause moderate discomfort. 
 Local or noninvasive intervention indicated. 
 More than minimal interference with ADLs but able to carry out daily social and 
functional activities. 
 Drug therapy may be required. 
Severe (could be non-serious or serious)  
 Symptoms causing severe discomfort/pain. 
 Symptoms requiring medical/surgical attention/intervention. 
 Interference with ADLs including inability to perform daily social and functional 
activities (eg, absenteeism and/or bed rest). 
 Drug therapy is required. 
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache). This criterion is not the same as “serious” which is based 
on subject/event outcome or action criteria associated with events that pose a threat to a subject’s 
life or functioning.  
Seriousness, not severity, serves as a guide for defining regulatory obligations. 

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10.2.3. 
Causality 
The Investigator must determine the relationship between the administration of the IP and the 
occurrence of an AE as Not Suspected or Suspected as defined below: 
Not suspected: 
A causal relationship of the adverse event to IP administration is 
unlikely or remote, or other medications, therapeutic 
interventions, or underlying conditions provide a sufficient 
explanation for the observed event. 
Suspected: 
There is a reasonable possibility that the administration of IP 
caused the adverse event. ‘Reasonable possibility’ means there 
is evidence to suggest a causal relationship between the IP and 
the adverse event. 
Causality should be assessed and provided for each AE based on currently available information. 
Causality is to be reassessed and provided as additional information becomes available. 
If an event is assessed as suspected of being related to a comparator, ancillary or additional non-
IP that has not been manufactured or provided by Amgen, please provide the name of the 
manufacturer when reporting the event. 
10.2.4. 
Duration 
For each AE, the Investigator will provide a record of the start and stop dates of the event. 
10.2.5. 
Action Taken 
The Investigator will report the action taken with IP as a result of each AE, as applicable (eg, 
discontinuation, interruption, or dose reduction of IP, as appropriate) and report if concomitant 
and/or additional treatments were given for the event.  
10.2.6. 
Outcome 
The Investigator will report the outcome of the event for each AE. 
All SAEs that have not resolved upon discontinuation of the subject’s participation in the study 
must be followed until recovered (returned to baseline), recovered with sequelae, or death (due to 
the SAE). 
10.3. 
Abnormal Laboratory Values 
An abnormal laboratory value is considered to be an AE if the abnormality: 
 Results in discontinuation from the study; 
 Requires treatment, modification/ interruption of IP dose, or any other therapeutic 
intervention; or 
 Is judged to be of significant clinical importance, eg, one that indicates a new disease 
process and/or organ toxicity or is an exacerbation or worsening of an existing 
condition. 

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Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event. 
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded as the AE. If the abnormality was not a part of a diagnosis or 
syndrome, then the laboratory abnormality should be recorded as the AE. If possible, the 
laboratory abnormality should be recorded as a medical term and not simply as an abnormal 
laboratory result (eg, record thrombocytopenia rather than decreased platelets). 
10.4. 
Pregnancy 
All pregnancies or suspected pregnancies occurring in a female subject of childbearing potential 
are immediately reportable events.   
10.4.1. 
Collection of Pregnancy and Infant Health Information 
Pregnancies and suspected pregnancies (including elevated -subunit of human chorionic 
gonadotropin [-hCG] or positive pregnancy test in a female subject of childbearing potential 
regardless of disease state) occurring while the subject is on IP, or within 28 days of the subject’s 
last dose of IP, must be reportable within 24 hours. Investigational product is to be discontinued 
immediately and the subject instructed to return any unused portion of the IP to the investigator.  
The pregnancy, suspected pregnancy, or positive pregnancy test must be reported to Amgen 
Global Patient Safety immediately by facsimile, email or other appropriate method, using the 
Pregnancy Notification Form or approved equivalent form (refer to Appendix X).  The 
Pregnancy Notification Form must be submitted to Amgen Global Patient Safety within 24 hours 
of learning of a subject’s pregnancy. (Note: Sites are not required to provide any information on 
the Pregnancy Notification Form that violates the country or regions local privacy laws).  
After obtaining the female subject’s signed consent for release of pregnancy and infant health 
information, the investigator will collect pregnancy and infant health information and complete 
the pregnancy questionnaire for any female subject who becomes pregnant while taking IP 
through 28 days of the subject’s last dose of IP. This information will be forwarded to Amgen 
Global Patient Safety. Generally, infant follow-up will be conducted 12 months after the birth of 
the child (if applicable). 
The female subject may be referred to an obstetrician-gynecologist or another appropriate 
healthcare professional for further evaluation. 
The Investigator will follow the female subject until completion of the pregnancy and must 
notify Amgen Global Patient Safety immediately about the outcome of the pregnancy (either 
normal or abnormal outcome). 
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the Investigator 
should report the abnormal outcome as an AE. If the abnormal outcome meets any of the serious 
criteria, it must be reported as an SAE to Amgen Global Patient Safety using the paper Serious 
Adverse Event Report Form within 24 hours of the Investigator’s knowledge of the event. 
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs. In addition, any infant death after 28 days that the Investigator suspects is 
related to in utero exposure to the IP should also be reported as an SAE to Amgen Global Patient 

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Safety by facsimile, email, or other appropriate method within 24 hours of the Investigator’s 
knowledge of the event, using the paper SAE Report form. 
10.4.2. 
Male Subjects With Partners Who Become Pregnant  
In the event a male subject fathers a child during treatment, and for an additional 28 days after 
discontinuing IP, the information will be recorded on the Pregnancy Notification Form (refer to 
Appendix V). The form must be submitted to Amgen Global Patient Safety with 24 hours of the 
investigator’s/site’s awareness of the pregnancy (Note: Sites are not required to provide any 
information on the Pregnancy Notification Form that violates the country or regions local 
privacy laws).  
The investigator will attempt to obtain a signed consent for release of pregnancy and infant 
health information directly from the pregnant female partner to obtain additional pregnancy 
information.    
After obtaining the female partner’s signed consent for release of pregnancy and infant health 
information the investigator will collect pregnancy outcome and infant health information on the 
pregnant partner and her baby and complete the pregnancy questionnaires. This information will 
be forwarded to Amgen Global Patient Safety.      
Generally, infant follow-up will be conducted up to 12 months after the birth of the child (if 
applicable).  
Any termination of the pregnancy will be reported to Amgen Global Patient Safety regardless of 
fetal status (presence or absence of anomalies) or indication for procedure. 
10.4.3. 
Collection of Lactation Information  
 Investigator will collect lactation information on any female subject who breastfeeds 
while taking IP through 28 days post last dose of IP.   
 Information will be recorded on the Lactation Notification Form (refer to Appendix Y) 
and submitted by facsimile or email to Amgen Global Patient Safety within 24 hours of 
the investigator’s knowledge of event.  
 Study treatment will be discontinued if female subject breastfeeds during the study. 
 With the female subject’s signed consent for release of mother and infant health 
information, the investigator will collect mother and infant health information and 
complete the lactation questionnaire on any female subject who breastfeeds while taking 
IP through 28 days after discontinuing IP. 
10.5. 
Reporting of Serious Adverse Events 
Any AE that meets any seriousness criterion for an SAE requires the reporting of an SAE within 
24 hours of the Investigator’s knowledge of the event. This instruction pertains to initial SAE 
reports as well as any follow-up reports. 
This requirement applies to all SAEs (regardless of relationship to IP) that occur during the study 
(from the time the subject signs informed consent until 28 days after the last dose of IP) and any 
SAE made known to the Investigator at any time following the protocol-required reporting 

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period or after end of study.  Serious adverse events occurring prior to treatment (after signing 
the ICF) are to be collected/recorded/reported.  
Where required by local legislation, the Investigator is responsible for informing the Institutional 
Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with all relevant 
initial and follow-up information about the event. The Investigator must keep copies of all SAE 
information on file including correspondence with Amgen and the IRB/EC. 
The SAE is recorded within the CRF and reported directly to Amgen Global Patient Safety by 
facsimile, email, or other appropriate method within 24 hours of the Investigator’s knowledge of 
the event, using the paper SAE Report form.  
Where required by local legislation, the Investigator is responsible for informing the Institutional 
Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with all relevant 
initial and follow-up information about the event. The Investigator must keep copies of all SAE 
information on file including correspondence with Amgen and the IRB/EC. 
Serious Adverse Event Reporting Transmitted Via Paper Serious Adverse Event Report 
Form:  
 Facsimile transmission of the SAE Report Form is the preferred method to transmit this 
information. If facsimile is unavailable, the email method to transmit this information is 
acceptable (refer to Appendix W). 
 In rare circumstances and in the absence of facsimile equipment, this form may be sent 
via email, or notification by telephone is acceptable with a copy of the Serious Adverse 
Event Report Form in English language sent by overnight mail or courier service.      
 Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE Report Form within the designated reporting timeframes.   
 Once the study has ended, serious adverse events (regardless of causality) should be 
reported to Amgen Global Patient Safety if the investigator becomes aware of them and 
may use the paper SAE Report Form (refer to Appendix W). 
10.5.1. 
Safety Queries 
Queries pertaining to SAEs will be communicated/generated from Amgen Global Patient Safety 
to the site via Amgen’s safety query paper process.  Pertaining to urgent queries (eg, missing 
causality assessment) these may be handled by phone, facsimile or email. 
10.6. 
Expedited Reporting of Adverse Events 
For the purpose of regulatory reporting, Amgen Global Patient Safety will determine the 
expectedness of events suspected of being related to apremilast based on the Investigator 
Brochure. 
In the United States, all suspected unexpected serious adverse reactions (SUSARs) will be 
reported in an expedited manner in accordance with 21 CFR 312.32.] 
For countries within the European Economic Area (EEA), Amgen or its authorized 
representative will report in an expedited manner to Regulatory Authorities and Ethics 

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Committees concerned, suspected unexpected serious adverse reactions (SUSARs) in accordance 
with Directive 2001/20/EC and the Detailed Guidance on collection, verification and 
presentation of adverse reaction reports arising from clinical trials on investigational products for 
human use (ENTR/CT3) and also in accordance with country-specific requirements.   
Amgen or its authorized representative shall notify the Investigator of the following information:  
 Any AE suspected of being related to the use of IP in this study or in other studies 
that is both serious and unexpected (ie, SUSAR); 
 Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity. 
Where required by local legislation, the Investigator shall notify his/her IRB/EC promptly of 
these new serious and unexpected AE(s) or significant risks to subjects. 
The Investigator must keep copies of all pertinent safety information on file including 
correspondence with Amgen and the IRB/EC. (See Section 14.3 for record retention 
information). 
Amgen Global Patient Safety Contact Information (fax/email): 
For Amgen Global Patient Safety contact information, please refer to your site’s paper SAE 
Report Form, paper Pregnancy Notification Form and/or paper Lactation Notification Form 
(Appendix W, Appendix X, Appendix Y). 

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11. 
DISCONTINUATIONS 
11.1. 
Treatment Discontinuation 
The following events are considered sufficient reasons for discontinuing a subject from the 
investigational product(s): 
 Adverse event(s) 
 Withdrawal by subject 
 Death 
 Lost to follow-up 
 Lack of efficacy 
 Non-compliance with study drug 
 Study terminated by Sponsor 
 Pregnancy 
 Death 
 Protocol deviation 
 Other (to be specified on the CRF) 
The reason for discontinuation of treatment should be recorded in the CRF and in the source 
documents. 
The decision to discontinue a subject from treatment can be taken at any time and remains the 
responsibility of the treating physician, which will not be delayed or refused by the Sponsor. 
However, prior to discontinuing a subject, the Investigator may contact the Medical Monitor and 
forward appropriate supporting documents for review and discussion. 
11.2. 
Study Discontinuation 
The following events are considered sufficient reasons for discontinuing a subject from the 
study: 
 Screen failure 
 Adverse event 
 Withdrawal by subject 
 Death 
 Loss to follow-up 
 Other (to be specified on the CRF) 
The reason for study discontinuation should be recorded in the CRF and in the source 
documents. 

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12. 
EMERGENCY PROCEDURES 
12.1. 
Emergency Contact 
In emergency situations, the Investigator should use their medical judgement to provide 
appropriate medical care of clinical trial subjects.  The Investigator may also contact 
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page). 
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, the investigator may also contact the Amgen Medical Information number at 
1-800-77-AMGEN (1 800-772-6436). The representatives are responsible for obtaining your 
call-back information and contacting the on-call /contract research organization Medical 
Monitor, who will then contact you promptly. 
12.2. 
Emergency Identification of Investigational Products 
The decision to break the blind in emergency situations remains the responsibility of the treating 
physician, which will not be delayed or refused by the Sponsor. However, the Investigator may 
contact the Medical Monitor prior to breaking the blind to discuss unblinding, mainly in the 
interest of the subject.  
The Investigator should ensure that the code is broken only in accordance with the protocol. The 
Investigator should promptly notify the Medical Monitor of the emergency unblinding and the 
reason for breaking the blind, which should be clearly documented by the Investigator in the 
subject’s source documentation. 
Emergency unblinding should only be performed by the Investigator through the Integrated 
Response Technology (IRT) by using an emergency unblinding personal identification number 
(PIN), and the Investigator should call IRT for unblinded dose information. Beginning at Week 
24 all subjects will be dispensed apremilast with titration in blinded treatment cards (Sections 7.3 
and 7.4). However, subjects will receive open-label apremilast at beginning at Week 28 until the 
end of the study, or until early discontinuation. Therefore, IP will be identified on the package 
labeling beginning at Week 28. 
 

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13. 
REGULATORY CONSIDERATIONS 
13.1. 
Good Clinical Practice 
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Amgen, its authorized representative, and 
Investigator abide by GCP, as described in ICH Guideline E6 and in accordance with the general 
ethical principles outlined in the Declaration of Helsinki. The study will receive approval from 
an IRB/EC prior to commencement. The Investigator will conduct all aspects of this study in 
accordance with applicable national, state, and local laws of the pertinent regulatory authorities. 
13.2. 
Investigator Responsibilities 
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations. Amgen staff or an authorized representative will evaluate and approve all 
Investigators who in turn will select their staff. 
The Investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions, 
including obligations of confidentiality of Amgen information. The Investigator should maintain 
a list of Sub-investigators and other appropriately qualified persons to whom he or she has 
delegated significant study-related duties. 
The Investigator is responsible for keeping a record of all subjects who sign an informed consent 
form (ICF) and are screened for entry into the study. Subjects who fail Screening must have the 
reason(s) recorded in the subject’s source documents. 
The Investigator, or a designated member of the Investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (eg, 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification. The Investigator must ensure timely and accurate completion of CRFs and queries. 
The information contained in the protocol and amendments (with the exception of the 
information provided by Amgen on public registry websites) is considered Amgen confidential 
information. Only information that is previously disclosed by Amgen on a public registry 
website may be freely disclosed by the Investigator or its institution, or as outlined in the Clinical 
Trial Agreement. Amgen protocol, amendment and IB information is not to be made publicly 
available (for example on the Investigator’s or their institution’s website) without express written 
approval from Amgen. Information proposed for posting on the Investigator’s or their 
institution’s website must be submitted to Amgen for review and approval, providing at least 5 
business days for review. 
At the time results of this study are made available to the public, Amgen will provide 
Investigators with a summary of the results that is written for the lay person. The Investigator is 
responsible for sharing these results with the subject and/or their caregiver as agreed by the 
subject. 

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13.3. 
Subject Information and Informed Consent 
The Investigator must obtain informed consent of a subject and/or a subject’s legal representative 
prior to any study related procedures. 
Documentation that informed consent occurred prior to the study subject’s entry into the study 
and of the informed consent process should be recorded in the study subject’s source documents 
including the date. The original ICF signed and dated by the study subject and by the person 
consenting the study subject prior to the study subject’s entry into the study, must be maintained 
in the Investigator’s study files and a copy given to the study subject. In addition, if a protocol is 
amended and it impacts on the content of the informed consent, the ICF must be revised. Study 
subjects participating in the study when the amended protocol is implemented must be re-
consented with the revised version of the ICF. The revised ICF signed and dated by the study 
subject and by the person consenting for the study subject must be maintained in the 
Investigator’s study files and a copy given to the study subject. 
13.4. 
Confidentiality 
Amgen affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Amgen requires 
the Investigator to permit Amgen's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local laws. 
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the Investigator to obtain such permission in 
writing from the appropriate individual. 
13.5. 
Protocol Amendments 
Any amendment to this protocol must be approved by the Amgen Clinical Research 
Physician/Medical Monitor. Amendments will be submitted to the IRB/EC for written approval. 
Written approval must be obtained before implementation of the amended version occurs. The 
written signed approval from the IRB/EC should specifically reference the Investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB/IEC approval but will be submitted to the IRB/IEC 
for information purposes. 
13.6. 
Institutional Review Board/Independent Ethics Committee Review 
and Approval 
Before the start of the study, the study protocol, ICF, and any other appropriate documents will 
be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their 
dates of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is 
sought. If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements. 
IP can only be supplied to an Investigator by Amgen or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 

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Amgen or its authorized representative. This documentation must also include a list of the 
members of the IRB/EC and their occupation and qualifications. If the IRB/EC will not disclose 
the names, occupations and qualifications of the committee members, it should be asked to issue 
a statement confirming that the composition of the committee is in accordance with GCP. For 
example, the IRB General Assurance Number may be accepted as a substitute for this list. 
Formal approval by the IRB/EC should mention the protocol title, number, amendment number 
(if applicable), study site (or region or area of jurisdiction, as applicable), and any other 
documents reviewed. It must mention the date on which the decision was made and must be 
officially signed by a committee member. Before the first subject is enrolled in the study, all 
ethical and legal requirements must be met. 
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised. 
The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating Investigator and the IRB/EC. This statement also applies to any 
communication between the Investigator (or Coordinating Investigator, if applicable) and 
regulatory authorities. 
Any advertisements used to recruit subjects for the study must be reviewed by Amgen and the 
IRB/EC prior to use.   
13.7. 
Ongoing Information for Institutional Review Board/ Ethics 
Committee 
If required by legislation or the IRB/EC, the Investigator must submit to the IRB/EC: 
 Information on serious or unexpected adverse events as soon as possible;  
 Periodic reports on the progress of the study; 
 Deviations from the protocol or anything that may involve added risk to subjects. 
13.8. 
Termination of the Study 
Amgen reserves the right to terminate this study prematurely at any time for reasonable medical 
or administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc). 
In addition, the Investigator or Amgen has the right to discontinue a single site at any time during 
the study for medical or administrative reasons such as: 
 Unsatisfactory enrollment; 
 GCP noncompliance; 
 Inaccurate or incomplete data collection; 
 Falsification of records; 
 Failure to adhere to the study protocol. 
 

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14. 
DATA HANDLING AND RECORDKEEPING  
14.1. 
Data/Documents 
The Investigator must ensure that the records and documents pertaining to the conduct of the 
study and the distribution of the investigational product are complete, accurate, filed and 
retained. Examples of source documents include: hospital records; clinic and office charts; 
laboratory notes; memoranda; subject’s diaries or evaluation checklists; dispensing records; 
recorded data from automated instruments; copies or transcriptions certified after verification as 
being accurate copies; microfiche; x-ray film and reports; and records kept at the pharmacy, and 
the laboratories, as well as copies of CRFs or CD-ROM. 
14.2. 
Data Management 
Data will be collected via CRF and entered into the clinical database per Amgen SOPs. This data 
will be electronically verified through use of programmed edit checks specified by the clinical 
team. Discrepancies in the data will be brought to the attention of the clinical team, and 
investigational site personnel, if necessary. Resolutions to these issues will be reflected in the 
database. An audit trail within the system will track all changes made to the data. 
14.3. 
Record Retention 
Essential documents must be retained by the Investigator according to the period of time outlined 
in the clinical trial agreement. The Investigator must retain these documents for the time period 
described above or according to local laws or requirements, whichever is longer. Essential 
documents include, but are not limited to, the following: 
 Signed ICFs for all subjects; 
 Subject identification code list, screening log (if applicable), and enrollment log; 
 Record of all communications between the Investigator and the IRB/EC; 
 Composition of the IRB/EC; 
 Record of all communications between the Investigator, Amgen, and their authorized 
representative(s); 
 List of Sub-investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures; 
 Copies of CRFs (if paper) and of documentation of corrections for all subjects; 
 IP accountability records; 
 Record of any body fluids or tissue samples retained; 
 All other source documents (subject records, hospital records, laboratory records, 
etc.);  
 All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial). 

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The Investigator must notify Amgen if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period. 
The Investigator must obtain approval in writing from Amgen prior to destruction of any records. 
If the Investigator is unable to meet this obligation, the Investigator must ask Amgen for 
permission to make alternative arrangements. Details of these arrangements should be 
documented.  
All study documents should be made available if required by relevant health authorities. 
Investigator or institution should take measures to prevent accidental or premature destruction of 
these documents. 
 

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15. 
QUALITY CONTROL AND QUALITY ASSURANCE 
All aspects of the study will be carefully monitored by Amgen or its authorized representative 
for compliance with applicable government regulations with respect to current GCP and SOPs. 
15.1. 
Study Monitoring and Source Data Verification 
Amgen ensures that appropriate monitoring procedures are performed before, during and after 
the study. All aspects of the study are reviewed with the Investigator and the staff at a study 
initiation visit and/or at an Investigators’ Meeting. Prior to enrolling subjects into the study, a 
Amgen representative will review the protocol, CRFs, procedures for obtaining informed 
consent, record keeping, and reporting of AEs/SAEs with the Investigator. Monitoring will 
include on-site visits with the Investigator and his/her staff as well as any appropriate 
communications by mail, email, fax, or telephone. During monitoring visits, the facilities, 
investigational product storage area, CRFs, subject’s source documents, and all other study 
documentation will be inspected/reviewed by the Amgen representative in accordance with the 
Study Monitoring Plan. 
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the CRFs against the appropriate source documentation. Any resulting 
discrepancies will be reviewed with the Investigator and/or his/her staff. Any necessary 
corrections will be made directly to the CRFs or via queries by the Investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified. Additional 
monitoring activities may be outlined in a study-specific monitoring plan. 
15.2. 
Audits and Inspections 
In addition to the routine monitoring procedures, a Quality, Compliance & Audit, Learning & 
Performance unit exists within Amgen. Representatives of this unit will conduct audits of clinical 
research activities in accordance with Amgen SOPs to evaluate compliance with Good Clinical 
Practice guidelines and regulations. 
The Investigator is required to permit direct access to the facilities where the study took place, 
source documents, CRFs and applicable supporting records of study subject participation for 
audits and inspections by IRB/ECs, regulatory authorities (eg, FDA, EMA, Health Canada) and 
company authorized representatives. The Investigator should make every effort to be available 
for the audits and/or inspections. If the Investigator is contacted by any regulatory authority 
regarding an inspection, he/she should contact Amgen immediately. 
15.3. 
Product Complaint 
A product complaint (PC) is any written, electronic, or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or 
performance of a drug, combination product or device after they are released for distribution to 
market or clinic by either Amgen or by distributors, and partners with whom Amgen 
manufactures the material.  This includes any drugs, devices, or combination products 
provisioned and/or repackaged/modified by Amgen.  Drugs or devices include investigational 
product.  Any product complaints associated with an investigational product, or non-

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investigational products or devices supplied by Amgen are to be reported according to the 
instructions provided in the Investigational Product Instruction Manual or equivalent.  
If you become aware of a suspected PC, you are obligated to report the issue within 24 hours of 
discovery or notification of the concern or irregularity.  Amgen requires notification of any 
concern or irregularity at any stage of the study. 
15.3.1. 
How to Report a Product Complaint to Amgen:   
Complete Amgen’s paper Clinical Product Complaint Intake Form and email the form to the 
following Amgen email address:  
Clinical-Complaint-Intake@amgen.com 
 

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16. 
PUBLICATIONS 
As described in Section 13.2, all protocol- and amendment-related information, with the 
exception of the information provided by Amgen on public registry websites, is considered 
Amgen confidential information and is not to be used in any publications. Amgen protocol-
related information proposed for use in a publication must be submitted to Amgen for review and 
approval and should not be utilized in a publication without express written approval from 
Amgen, or as described in the Clinical Trial Agreement. 
Amgen will ensure Amgen-sponsored studies are considered for publication in the scientific 
literature in a peer-reviewed journal, irrespective of the results. At a minimum, this applies to 
results from all Phase 2 and Phase 3 clinical studies, and any other study results of significant 
medical importance. This also includes results relating to investigational medicines whose 
development programs have been discontinued. 
Study results may also be presented at one or more medical congresses and may be used for 
scientific exchange and teaching purposes. Additionally, this study and its results may be 
submitted for inclusion in all appropriate health authority study registries, as well as publication 
on health authority study registry websites, as required by local health authority regulations. 
Eligibility for authorship will be in alignment with ICMJE authorship criteria and be based on 
several considerations, including, but not limited to, contribution to protocol development, study 
recruitment, data quality, participation in data analysis, and contribution to abstract, presentation 
and/or publication development. 
 

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17. 
REFERENCES 
Aletaha D, Smolen JS. The definition and measurement of disease modification in inflammatory 
rheumatic diseases. Rheum Dis Clin North Am. 2006;32(1):9-44, vii. 
Annual Scientific Meeting of the American College of Rheumatology; 10/2011; Chicago, IL; 
November 4-9, 20112011. p. S153. 
Bruce B, Fries JF. The Stanford Health Assessment Questionnaire: a review of its history, issues, 
progress, and documentation. J Rheumatol. 2003;30(1):167-78. 
Coates LC, FitzGerald O, Gladman DD, McHugh N, Mease P, Strand V, et al. Reduced joint 
counts misclassify patients with oligoarticular psoriatic arthritis and miss significant numbers of 
patients with active disease. Arthritis Rheum. 2013;65(6):1504-9. 
Coates LC, Helliwell PS. Methotrexate Efficacy in the Tight Control in Psoriatic Arthritis Study. 
J Rheumatol. 2016;43(2):356-61. 
Coates LC, Mahmood F, Emery P, Conaghan PG, Helliwell PS. The dynamics of response as 
measured by multiple composite outcome tools in the TIght Control of inflammation in early 
Psoriatic Arthritis (TICOPA) trial. Ann Rheum Dis. 2017;76(10):1688-92. 
Coates LC, Cook R, Lee A, Chandran V, Gladman D. Frequency, predictors, and prognosis of 
sustained minimal disease activity in an observational psoriatic arthritis cohort. Arthritis Care & 
Research, 2010,62, (7): 970–976. 
Cutolo M, Myerson GE, Fleischmann R, Liote F, Diaz-Gonzalez F, Van den Bosch F, et al. A 
phase III, randomized, controlled trial of apremilast in patients with psoriatic arthritis: results of 
the PALACE 2 trial. J Rheumatol. 2016;43(9):1724-34. 
Edwards CJ, Blanco FJ, Crowley J, Birbara CA, Jaworski J, Aelion J, et al. Apremilast, an oral 
phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a 
phase III, randomised, controlled trial (PALACE 3). Ann Rheum Dis. 2016;75(6):1065-73. 
Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, et al. American College 
of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis 
Rheum. 1995;38(6):727-35. 
Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. 
Arthritis Rheum. 1980;23(2):137-45. 
Gladman D, Antoni C, Mease P, Clegg D, Nash P. Psoriatic arthritis: epidemiology, clinical 
features, course and outcome. Ann Rheum Dis 2005;64(Suppl II):ii14–ii17. doi: 
10.1136/ard.2004.032482. 
Gossec L, de Wit M, Kiltz U, Braun J, Kalyoncu U, Scrivo R, et al. A patient-derived and 
patient-reported outcome measure for assessing psoriatic arthritis: elaboration and preliminary 
validation of the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire, a 13-country 
EULAR initiative. Ann Rheum Dis. 2014;73(6):1012-9. 
Gossec L, Smolen JS, Ramiro S, De Wit M, Cutolo M, Dougados M, et al. European League 
Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with 
pharmacological therapies: 2015 update. Ann Rheum Dis. 2016;75(3):499-510. 

Apremilast 
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CC-10004-PSA-013 Amendment 4 Final: 12 July 2021 
Healy PJ, Helliwell PS. Measuring clinical enthesitis in psoriatic arthritis: assessment of existing 
measures and development of an instrument specific to psoriatic arthritis. Arthritis Rheum. 
2008;59(5):686-91. 
Helliwell PS, Firth J, Ibrahim GH, Melsom RD, Shah I, Turner DE. Development of an 
assessment tool for dactylitis in patients with psoriatic arthritis. J Rheumatol. 2005;32(9):1745-
50. 
Helliwell PS, Porter G, Taylor WJ. Polyarticular psoriatic arthritis is more like oligoarticular 
psoriatic arthritis, than rheumatoid arthritis. Ann Rheum Dis. 2007;66 (1):113-7. 
Helliwell PS, FitzGerald O, Fransen J. Composite disease activity and responder indices for 
psoriatic arthritis: a report from the GRAPPA, 2013 meeting on development of cutoffs for both 
disease activity states and response.  J Rheumatol 2014, 41;1212-1217. 
Jones SM, Armas JB, Cohen MG, Lovell CR, Evison G, McHugh NJ. Psoriatic arthritis: 
outcome of disease subsets and relationship of joint disease to nail and skin disease. Br J 
Rheumatol. 1994;33(9):834-9. 
Kane D, Stafford L, Bresnihan B, FitzGerald O. A classification study of clinical subsets in an 
inception cohort of early psoriatic peripheral arthritis--'DIP or not DIP revisited'. Rheumatology 
(Oxford). 2003;42(12):1469-76. 
Kavanaugh A, Gladman DD, Gomez-Reino JJ, Hall S, Lespessailles E, Mease PJ, et al. 
Durability of apremilast response through 5 years of treatment of subjects with psoriatic arthritis 
[abstract]. Presented at the Annual Meeting of the American Academy of Dermatology; February 
16-20, 2018, San Diego, CA. 
Kavanaugh A, Gladman DD, Gomez-Reino JJ, Hall S, Lespessailles E, Mease PJ, et al. 
Durability of apremilast response through 5 years of treatment in subjects with psoriatic arthritis 
[poster 6336]. Annual Meeting of the American Academy of Dermatology; February 16-20, 
2018, San Diego, CA. 
Kavanaugh A, Mease PJ, Gomez-Reino JJ, Adebajo AO, Wollenhaupt J, Gladman DD, et al. 
Treatment of psoriatic arthritis in a phase 3 randomized, placebo-controlled trial with apremilast, 
an oral phosphodiesterase 4 inhibitor. Ann Rheum Dis. 2014;73(6):1020-6. 
Kruithof E, Baeten D, De Rycke L, Vandooren B, Foell D, Roth J, Cañete J, Boots A, Veys M, 
De Keyser F. Synovial histopathology of psoriatic arthritis, both oligo- and polyarticular, 
resembles spondyloarthropathy more than it does rheumatoid arthritis. Arthritis Res Ther. 2005, 
7:R569-R580 (DOI 10.1186/ar1698). 
Lindqvist UR, Alenius GM, Husmark T, Theander E, Holmstrom G, Larsson PT. The Swedish 
early psoriatic arthritis register--2-year followup: a comparison with early rheumatoid arthritis. J 
Rheumatol. 2008;35(4):668-73. 
Maksymowych WP, Mallon C, Morrow S, Shojania K, Olszynski WP, Wong RL, et al. 
Development and validation of the Spondyloarthritis Research Consortium of Canada 
(SPARCC) Enthesitis Index. Ann Rheum Dis. 2009;68(6):948-53. 
Mease, PJ, et al. How much improvement in functional status is considered important by patients 
with active psoriatic arthritis: applying the outcome measures in rheumatoid arthritis clinical 
trials (omeract) group guidelines. EULAR, 2004, LI SAT0015. 

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Mease PJ, Gladman DD, Davenport EK, Zhou X, Guerette B, Teng L, et al. Improvements in 
work productivity with up to 104 weeks of apremilast monotherapy: results from a phase 3b, 
randomized, controlled study in biologic-naive subjects with active psoriatic arthritis [abstract]. 
Arthritis Rheumatol. 2017;69(suppl 10):602. 
Moll JM, Wright V. Psoriatic arthritis. Semin Arthritis Rheum. 1973;3(1):55-78. 
Nash P, Ohson K, Walsh J, Delev N, Nguyen D, Teng L, et al. Early and sustained efficacy with 
apremilast monotherapy in biological-naive patients with psoriatic arthritis: a phase IIIB, 
randomised controlled trial (ACTIVE). Ann Rheum Dis. 2018;77:690-8. 
Pham,T. Patient acceptable symptomatic state (PASS). Joint Bone Spine 76 (2009) 321e323. 
Reilly MC, Gooch KL, Wong RL, Kupper H, van der Heijde D. Validity, reliability and 
responsiveness of the Work Productivity and Activity Impairment Questionnaire in ankylosing 
spondylitis. Rheumatology (Oxford). 2010;49(4):812-9. 
Ritchlin CT, Colbert RA, Gladman DD. Psoriatic Arthritis. N Engl J Med. 2017;376(10):957-70. 
Roberts ME, Wright V, Hill AG, Mehra AC. Psoriatic arthritis. Follow-up study. Ann Rheum 
Dis. 1976;35(3):206-12. 
Schafer PH, Chen P, Fang L, Wang A, Chopra R. The pharmacodynamic impact of apremilast, 
an oral phosphodiesterase 4 inhibitor, on circulating levels of inflammatory biomarkers in 
patients with psoriatic arthritis: substudy results from a phase III, randomized, placebo-
controlled trial (PALACE 1). J Immunol Res. 2015;2015:906349. doi: 10.1155/2015/. 
Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H. Classification criteria 
for psoriatic arthritis: development of new criteria from a large international study. Arthritis 
Rheum. 2006;54(8):2665-73. 
The EuroQol Group. EuroQol--a new facility for the measurement of health-related quality of 
life. Health Policy. 1990;16(3):199-208. 
Tubach F, Pham T, Skomsvoll JF, Mikkelsen K, Bjorneboe O, Ravaud P, et al. Stability of the 
patient acceptable symptomatic state over time in outcome criteria in ankylosing spondylitis. 
Arthritis Rheum. 2006;55(6):960-3. 
van Vollenhoven R F, Cifaldi MA, Saurabh R; Chen N, Weisman M H. Improvement in work 
place and household productivity for patients with early rheumatoid arthritis treated with 
adalimumab plus methotrexate: work outcomes and their correlations with clinical and 
radiographic measures from a randomized controlled trial companion study. American College 
of Rheumatology 2010,62, (2) 226–234. 
Ware JE, Jr., Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual 
framework and item selection. Med Care. 1992;30(6):473-83. 
Wells AF, Edwards CJ, Kivitz AJ, Bird P, Nguyen D, Paris M, et al. Long-tern (4-year) efficacy 
and safety of apremilast monotherapy in DMARD-naive subjects with active psoriatic arthritis. 
Arthritis Rheumatol. 2018;69 (suppl 10):601. 
Wolf, F, et al. The American College of Rheumatology preliminary diagnostic criteria for 
fibromyalgia and measurement of symptom severity. Arthritis Care Res 62(5):600-610, 2010. 

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World Health Organization. Diarrhoea. Available at http://www.who.int/topics/diarrhoea/en/. 
Accessed November 27, 2013. 
 

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18. 
APPENDICES 
Appendix A: Table of Abbreviations 
Abbreviation or 
Specialist Term 
Explanation 
ACR20/50/70 
American College of Rheumatology 20/50/70 response 
improvement 
ADL 
Activity of daily life  
AE 
Adverse event 
ALT 
Alanine aminotransferase (SGPT) 
ANC 
Absolute neutrophil count 
APR 
Parmalat  
AST 
Aspartate aminotransferase (SGOT) 
AUC 
Area under the curve 
-hCG 
-subunit of human chorionic gonadotropin 
bDMARD 
Biologic disease-modifying antirheumatic drug 
BID 
Twice daily 
BSA 
Body surface area 
BUN 
Blood urea nitrogen 
cAMP 
Cyclic adenosine monophosphate 
CASPAR 
Classification Criteria for Psoriatic Arthritis 
CBC 
Complete blood count 
cDAPSA 
Clinical disease activity in psoriatic arthritis (without measuring C-
reactive protein [CRP]) 
CI 
Confidence interval 
CL 
Clearance 
Cmax 
Maximum plasma concentration of drug 
CNS 
Central nervous system 
CRO 
Contract research organization 
CRF 
Case report form 
CRP 
C-reactive protein 
csDMARD 
Conventional synthetic disease-modifying antirheumatic drug: 
antirheumatic drugs designed in a traditional way, such as methotrexate or 
sulfasalazine 
CT 
Computed tomography 

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Abbreviation or 
Specialist Term 
Explanation 
DIP 
Distal interphalangeal 
DLT 
Dose-limiting toxicity 
DMARD 
Disease-modifying antirheumatic drug 
DMC 
Data Monitoring Committee 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic Data Capture 
EE 
Early escape 
EEA 
European Economic Area 
EMA 
European Medicines Agency 
EOT 
End of treatment 
FAS 
Full analysis set  
FCBP 
Females of childbearing potential 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GEI 
Gladman Enthesitis Index 
HAQ-DI 
Health Assessment Questionnaire Disability Index 
HDPE 
High-density polyethylene 
HIV 
Human immunodeficiency virus 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Council on Harmonisation 
IL 
Interleukin  
IM 
Intra-muscular 
IND 
Investigational New Drug 
IP 
Investigational Product 
IRB 
Institutional Review Board 
IRT 
Integrated Response Technology 

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Abbreviation or 
Specialist Term 
Explanation 
IWRS 
Interactive Web Response System 
IV 
Intravenous 
LEF 
Leflunomide 
LEI 
Leeds Enthesitis Index 
LVEF 
Left ventricular ejection fraction 
LOCF 
Last observation carried forward 
LS mean 
Least squares mean 
MASES 
Maastricht Ankylosing Spondylitis Enthesitis Score 
MCID 
Minimal clinically important difference 
MDA 
Minimal disease activity 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIP 
Macrophage inflammatory protein 
MMRM 
Mixed-effects model for repeated measures 
MRI 
Magnetic resonance imaging 
MTD 
Maximum tolerated dose 
MTX 
Methotrexate 
MUGA 
Multi-gated acquisition 
NCI 
National Cancer Institute 
NRI 
Nonresponder imputation 
NSAID 
Nonsteroidal anti-inflammatory drug 
PSAID 
Psoriatic Arthritis Impact of Disease  
PASDAS 
Psoriatic Arthritis Disease Activity Score 
PASI 50/70 
 50/75 improvement in the Psoriasis Area and Severity Index 
PBO 
Placebo  
PDE 
Phosphodiesterase enzyme 
PRO 
Patient-reported outcome 
PsA 
Psoriatic arthritis 
PsAID 
Psoriatic arthritis impact of disease 
PC 
Product Complaint  

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Abbreviation or 
Specialist Term 
Explanation 
QOL 
Quality of life 
RBC 
Red blood cell count 
RF 
Rheumatoid factor 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SC 
Steering committee 
SE 
Standard error 
SGOT 
Serum glutamic oxaloacetic transaminase  
SGPT 
Serum glutamic pyruvic transaminase 
SJC 
Swollen joint count 
SOP 
Standard operating procedure 
SpA 
Seronegative spondyloarthropathy 
SSZ 
Sulfasalazine  
SUSAR 
Suspected unexpected serious adverse reaction 
T½  
Half-life 
TC 
Total cholesterol 
TEAE 
Treatment-emergent adverse event 
TB 
Tuberculosis  
TID 
Three times daily 
TJC 
Tender joint count 
TNF 
Tumor necrosis factor 
ULN 
Upper limit of normal 
USA 
United States of America 
USP 
United States Pharmacopeia 
VAS 
Visual analog scale 
VLDA 
Very low disease activity 
Vss 
Volume of distribution 
WBC 
White blood cell count 

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Appendix B: The CASPAR Criteria 
To meet the CASPAR1 (Classification criteria for Psoriatic Arthritis) criteria, a patient must have 
inflammatory articular disease (joint, spine, or entheseal) with  3 points from the following 5 
categories: 
1. Evidence of current psoriasis, a personal history of psoriasis, or a family history of 
psoriasis. 
 Current psoriasis is defined as psoriatic skin or scalp disease present today as judged 
by a rheumatologist or dermatologist.2 
 A personal history of psoriasis is defined as a history of psoriasis that may be 
obtained from a patient, family physician, dermatologist, rheumatologist, or other 
qualified health care provider. 
 A family history of psoriasis is defined as a history of psoriasis in a first- or second-
degree relative according to patient report. 
2. Typical psoriatic nail dystrophy including onycholysis, pitting, and hyperkeratosis 
observed on current physical examination. 
3. A negative test result for the presence of rheumatoid factor by any method except latex 
but preferably by enzyme-linked immunosorbent assay or nephelometry, according to the 
local laboratory reference range. 
4. Either current dactylitis, defined as swelling of an entire digit, or a history of dactylitis 
recorded by a rheumatologist. 
5. Radiographic evidence of juxtaarticular new bone formation, appearing as ill-defined 
ossification near joint margins (but excluding osteophyte formation) on plain radiographs 
of the hand or foot. 
 
                                                          
1 The CASPAR criteria have specificity of 98.7% and sensitivity of 91.4%. 
2 Current psoriasis is assigned a score of 2; all other features are assigned a score of 1  
(from Taylor, 2006). 

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Appendix C: Modified Minimal Disease Activity (MDA-Joints) Assessment 
To meet the mMDA-Joints criteria, a patient must achieve  1 SJC and TJC, plus 3 out of 5 of 
the following cut-off values: 
1. Patient’s global disease activity (VAS, 0-100 mm)  20 
2. Patient’s pain (VAS, 0-100 mm)  15 
3. HAQ  0.5 
4. Tender entheseal points  1 (Based on the Leeds Enthesitis Index - LEI)  
5. BSA  3 
 

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Appendix D: Joint Assessment - 68 and 66 Joint Counts 
 
68 Joint Score: Upper Extremity Joint Counts 
Please write in the appropriate code for every joint using the Pain/Tenderness and Swelling Codes. 
Pain/Tenderness Codes 
Swelling Codes 
N  No pain/tenderness 
N  No swelling 
Y  Pain/tenderness 
Y  Swelling 
ND  Not Done 
ND  Not Done 
Joints that are swollen and tender should be marked with a tick. If a joint is injected with intra-
articular glucocorticoid, this joint should be marked by an X for the next 4 weeks 
 
Joints 
Right Side 
Left Side 
Pain/Tenderness 
Swelling 
Pain/Tenderness 
Swelling 
Y    N    ND 
Y    N    ND 
Y    N    ND 
Y    N    ND 
Temporomandibular 
 
 
 
 
Sternoclavicular 
 
 
 
 
Acromioclavicular 
 
 
 
 
Shoulder 
 
 
 
 
Elbow 
 
 
 
 
Wrist 
 
 
 
 
MCP 1 
 
 
 
 
MCP 2 
 
 
 
 
MCP 3 
 
 
 
 
MCP 4 
 
 
 
 
MCP 5 
 
 
 
 
PIP 1 
 
 
 
 
PIP 2 
 
 
 
 
PIP 3 
 
 
 
 
PIP 4 
 
 
 
 
PIP 5 
 
 
 
 
DIP 2 
 
 
 
 
DIP 3 
 
 
 
 
DIP 4 
 
 
 
 
DIP 5 
 
 
 
 
 

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Appendix D: Joint Assessment – 68 and 66 Joint Counts (Continued) 
 
68 Joint Score:  Lower Extremity Joint Counts 
Please write in the appropriate code for every joint using the Pain/Tenderness and Swelling Codes. 
Pain/Tenderness Codes 
Swelling Codes 
N  No pain/tenderness 
N  No swelling 
Y  Pain/tenderness 
Y  Swelling 
ND  Not Done 
ND Not Done 
 
 
Joints 
Right Side 
Left Side 
Pain/Tenderness 
Swelling 
Pain/Tenderness 
Swelling 
Y    N    ND 
Y    N    ND 
Y    N    ND 
Y    N    ND 
Hip 
 
 
 
 
Knee 
 
 
 
 
Ankle 
 
 
 
 
Mid-tarsal 
 
 
 
 
MTP 1 
 
 
 
 
MTP 2 
 
 
 
 
MTP 3 
 
 
 
 
MTP 4 
 
 
 
 
MTP 5 
 
 
 
 
PIP 1 
 
 
 
 
PIP 2 
 
 
 
 
PIP 3 
 
 
 
 
PIP 4 
 
 
 
 
PIP 5 
 
 
 
 
 
 

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Appendix E:
Visual Analog Scale
Scales depicted below are on 0-100 mm scale. Note that for the cDAPSA (Appendix K), both 
;(0+):G9':/+4:G925('299+993+4:5,/9+'9+):/</:?'4*;(0+):G999+993+4:5,'/4
scales will be on 0-10 cm scale. 
Evaluators Global Assessment of Disease Activity
+!*0)* %*0)#&#))))$%*& ))* , *.
+!*0) Assessment of Pain
From Felson, 1995.

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Appendix F: Disability Index of the Health Assessment Questionnaire 
(HAQ-DI)  
 
 

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Appendix F: Disability Index of the Health Assessment Questionnaire  
(HAQ-DI) (Continued)  
 
Source: Bruce, 2003. 

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Appendix G: Leeds Enthesitis Index (LEI)  
Leeds Enthesitis Index: 
Enthesitis is measured by physical examination of the joints below. Tenderness will be assessed 
at the following entheses (tendon insertions) as depicted below:  
1. Lateral epicondyle humerus, left and right 
2. Medial condyle femur, left and right 
3. Achilles tendon insertion into calcaneum, left and right 
Tenderness on physical examination is recorded as either present (1) or absent (0) for each of the 
6 sites, for an overall score range of 0 to 6. Higher count represents a greater enthesitis burden. 
 
 

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Appendix H: Body Surface Area (BSA) 
BSA is a measure of involved skin. The overall BSA affected by psoriasis is estimated based on 
the palm area of the subject’s hand (entire palmar surface or “handprint”), which equates to 
approximately 1 of the total body surface area. 
Tutorial is available at http://www.pasitraining.com/bsa_score/ 
 

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Appendix K: C-Disease Activity index for Psoriatic Arthritis (cDAPSA)  
The cDAPSA score assesses four domains (Tender Joint Counts [TJC] and Swollen Joint Counts 
[SJC] using 66/68 joints count, patient’s global VAS on a 10-cm scale, patient’s pain VAS on a 
10-cm scale. The cDAPSA is calculated by summing swollen  tender joint counts  patient pain 
 patient global assessments. 
The cDAPSA score can be used to effectively separate the disease states of remission (REM), 
low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA) 
by specific cutpoints detailed below: 
REM: cDAPSA4; LDA: 4cDAPSA13; MDA: 13cDAPSA27; HDA: cDAPSA27. 
 

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Appendix L: Psoriatic Arthritis Disease Activity Score (PASDAS) 
The PASDAS is a weighted index comprising assessments of joints, physical function, acute-
phase response, patient and physician global assessment of the disease, enthesitis and dactylitis. 
It is represented by the formula: 
PASDAS  ((0.18 x Physician global VAS)  (0.159 x Patient global VAS) – (0.253 x SF36 
– PCS)  (0.101 x LN (Swollen joint count  1))  (0.048 x LN (Tender joint count  1))  (0.23 
x LN (Leeds Enthesitis Count  1))  (0.377 x LN (Dactylitis count  1))  (0.102 x LN (CRP  
1))2)*1.5 
CRP  C-reactive protein in mg/l, LN  natural logarithm, SF36  Medical Outcomes Study 
Short Form-36, SF36-PCS  physical component summary scale of SF36. All VAS scores are 
0-100 mm. Swollen joint count is 66 joints, and tender joint count 68. The score range of the 
PASDAS is 0–10, with worse disease activity represented by higher scores.  
Definition of good or moderate response is detailed in the table below: 
Response criteria for the Psoriatic Arthritis Disease Activity Score (PASDAS). 
 
 
Improvement 
 
Final PASDAS Score 
 1.6 
 1.6 but  0.8 
 0.8 
 3.2 
1 
2 
3 
 3.2 but  5.4 
2 
2 
3 
 5.4 
2 
3 
3 
1  good response; 2  moderate response; 3  poor response 
 

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Appendix N: The PsA Impact of Disease 12-Item (PsAID-12) Questionnaire 
The PsAID-12 Questionnaire (Gossec, 2014) is a 12-item, self-administered questionnaire that 
reflects the impact of PsA from the perspective of the patient. It is composed of 12 physical and 
psychological domains. Each domain is rated from 0 to 10 with a different weighting. The total 
score is divided by 20. The final score has a range from 0 (best status) to 10 (worst status), with a 
cut-off of 4.  
We want you to indicate how much your psoriatic arthritis impacts your health. Please tell us 
how you have been feeling this last week.  
1. Pain  
Circle the number that best describes the pain you felt due to your psoriatic arthritis during the 
last week: 
 
2. Fatigue  
Circle the number that best describes the overall level of fatigue due to your psoriatic arthritis 
you have experienced during the last week:  
 
3. Skin problems  
Circle the number that best describes the skin problems including itching you felt due to your 
psoriatic arthritis during the last week:  
 
4. Work and/or leisure activities  
Circle the number that best describes the difficulties you had to participate fully in work and/or 
leisure activities due to your psoriatic arthritis during the last week: 
 
None 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Extreme 
No 
fatigue 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Totally 
exhausted 
None 
0  
1  
2  
3  
4  
5  
6  
7  
8  
9  
10  
Extreme 
None 
0  
1  
2  
3  
4  
5  
6  
7  
8  
9  
10  
Extreme 

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Appendix N: The PsA Impact of Disease 12-Item (PsAID-12) Questionnaire 
(Continued) 
5. Functional capacity  
Circle the number that best describes the difficulty you had in doing daily physical activities due 
to your psoriatic arthritis during the last week:  
 
6. Discomfort  
Circle the number that best describes the feeling of discomfort and annoyance with everyday 
tasks due to your psoriatic arthritis during the last week: 
 
7. Sleep disturbance  
Circle the number that best describes the sleep difficulties (ie, resting at night) you felt due to 
your psoriatic arthritis during the last week:  
 
8. Coping  
Considering your psoriatic arthritis overall, how well did you cope (manage, deal, make do) with 
your psoriatic arthritis during the last week?   
 
 
No 
difficulty 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Extreme 
difficulty 
None 
0  
1  
2  
3  
4  
5  
6  
7  
8  
9  
10  
Extreme 
No 
difficulty 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Extreme 
difficulty 
Very 
well 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Very 
poorly 

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Appendix N: The PsA Impact of Disease 12-Item (PsAID-12) Questionnaire 
(Continued) 
9. Anxiety, fear and uncertainty  
Circle the number that best describes the level of anxiety, fear and uncertainty (for example 
about the future, treatments, fear of loneliness) due to your psoriatic arthritis you have 
experienced during the last week:  
 
10. Embarrassment and/or shame 
Considering your psoriatic arthritis overall, circle the number that best describes the level of 
embarrassment and/or shame due to your appearance experienced during the last week: 
 
11. Social participation 
Circle the number that best describes the difficulties you had to participate fully in social 
activities (including relationships with family and/or people very close to you) due to your 
psoriatic arthritis during the last week: 
 
12. Depression 
Circle the number that best describes the level of depression due to your psoriatic arthritis you 
have experienced during the last week: 
 
THANK YOU FOR ANSWERING THIS QUESTIONNAIRE. 
 
None 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Extreme 
None 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Extreme 
None 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Extreme 
None 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Extreme 

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Appendix N: The PsA Impact of Disease 12-Item (PsAID-12) Questionnaire 
(Continued) 
PsAID-12 SCORING AND CALCULATION RULES  
The PsAID is calculated based on 12 NRS questions. Each NRS is assessed as a number between 
0 and 10.  
Calculators and translations are available at 
http://www.eular.org/index.cfm?framePage/st_com_clinical_tools.cfm. 
1. Calculation   
PsAID final value   
(PsAID1 (pain) NRS value (range 0-10) x 3)  
 (PsAID2 (fatigue) NRS value (range 0-10) x 2)  
 (PsAID3 (skin) NRS value (range 0-10) x 2)  
 (PsAID4 (Work and/or leisure activities) NRS value (range 0-10) x 2)  
 (PsAID5 (function) NRS value (range 0-10) x 2)  
 (PsAID6 (discomfort) NRS value (range 0-10) x 2)  
 (PsAID7 (sleep) NRS value (range 0-10) x 2)  
 (PsAID8 (coping) NRS value (range 0-10) x 1)  
 (PsAID9 (anxiety) NRS value (range 0-10) x 1)  
 (PsAID10 (embarrassment) NRS value (range 0-10) x 1)  
 (PsAID11 (social life) NRS value (range 0-10) x 1)  
 (PsAID12 (depression) NRS value (range 0-10) x 1)  
 
The total is divided by 20. Thus, the range of the final PsAID value is 0-10, where 
higher figures indicate worse status.  
 
 
2.  Missing data imputation  
If one of the 12 NRS values composing the PsAID is missing, the imputation is as follows: 
a. calculate the mean value of the 11 other (non-missing) NRS values (range, 0-10) 
b. impute this value for the missing NRS value 
c. then, calculate the PsAID score as explained above.  
 
If 2 or more of the NRS values are missing, the PsAID score is considered a missing value 
(no imputation). 
 

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Appendix T: Blister Card Configurations 
 
 
 
 

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Appendix T: Blister Card Configurations (Continued) 
 
 

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Appendix W: Sample Serious Adverse Event Report Form 
 

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Appendix W: Sample Serious Adverse Event Report Form (Continued) 
 

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Appendix W: Sample Serious Adverse Event Report Form (Continued) 

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Appendix X: Pregnancy Notification Form 

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Appendix Y: Lactation Notification Form 

Product:  Apremilast 
Protocol Number:  20200058 
Date:  12 July 2021 
Page 1 of 9 
Amgen Proprietary - Confidential 
Confidential 
 
Amendment 5 
Protocol Title:  A PHASE 4, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY TO EVALUATE THE 
EFFICACY AND SAFETY OF APREMILAST (CC-10004) IN SUBJECTS WITH 
EARLY, OLIGOARTICULAR PSORIATIC ARTHRITIS DESPITE INITIAL STABLE 
TREATMENT WITH EITHER NSAIDS AND/OR  1 CONVENTIONAL SYNTHETIC 
DMARD 
 
Amgen Protocol Number Apremilast CC-1004-PSA-013 20200058 
EudraCT Number:  2018-002735-26 
IND Number:  101761 
NCT Number:  NCT03747939 
 
Amendment Date: 
12 July 2021 
Rationale: 
The rationale of this protocol amendment is to include following updates: 
 
To update the total number of subjects to be randomized in the study in all the 
sections wherever applicable. 
 
To update the inclusion criteria to update language as symptoms of psoriatic 
arthritis (PsA) with oligoarthritis by any criteria with no minimum time 
constraint. 
 
To update the study rationale to include subjects with early diagnosis of PsA 
( 5 years since signs and symptoms began). 
 
To update the exclusion criteria for prior use of 2 conventional synthetic 
disease-modifying antirheumatic drugs. 
 
To update the exclusion criteria to change the bacterial infections requiring 
treatment within 1 week of Screening. 
 
To update the table of events table to include  7 days for observational 
follow-up visit. 
 
To update the statistical sample size of approximately 
 for the 
active and placebo groups. 

Apremilast 
Summary of Changes CC-10004-PSA-013 
Amgen Inc. 
Amgen Proprietary - Confidential 
Confidential and Proprietary 
1 
    CC-10004-PSA-013 Amendment 4 Final: 03 February 2021 
– SUMMARY OF CHANGES – 
A PHASE 4, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY TO 
EVALUATE THE EFFICACY AND SAFETY OF APREMILAST 
(CC-10004) IN SUBJECTS WITH EARLY, OLIGOARTICULAR 
PSORIATIC ARTHRITIS DESPITE INITIAL STABLE 
TREATMENT WITH EITHER NSAIDS AND/OR  1 
CONVENTIONAL SYNTHETIC DMARD 
AMENDMENT NO. 4 
INVESTIGATIONAL PRODUCT (IP): 
 
Apremilast 
PROTOCOL NUMBER: 
 
CC-10004-PSA-013 
ORIGINAL DATE: 
 
09 JUL 2018  
AMENDMENT 1 DATE 
 
05 FEB 2019 
AMENDMENT 2 DATE: 
 
17 MAY 2019  
AMENDMENT 3 DATE: 
 
04 MAY 2020 
AMENDMENT 4 DATE: 
 
03 FEB 2021 
EudraCT NUMBER: 
 
2018-002735-26 
IND NUMBER:  
 
101761 
NCT NUMBER 
 
NCT03747939 
Contact Information:  
 
 
Name: 
, MD 
 
Title: 
Medical Director Global Development 
Amgen Inc. 
 
Address:  
Amgen Inc, 
Amgen Center Dr, Thousand Oaks, CA 91320 
USA 
 
Phone: 
 
E-mail: 
Note: Only call Amgen Medical Information, if you are not able to reach the 
Clinical Research Physician(s) or Medical Monitor or designee for emergency calls. 
 
Confidentiality Notice 
This document contains confidential information of Amgen. This document must not be disclosed to 
anyone other than the site study staff and members of the institutional review board/independent 
ethics committee/institutional scientific review board or equivalent. The information in this document 
cannot be used for any purpose other than the evaluation or conduct of the clinical investigation 
without the prior written consent of Amgen. If you have questions regarding how this document may 
be used or shared, call the Amgen Medical Information number: 1- 800-77-AMGEN 
Amgen Medical Information:  1- 800-77-AMGEN (1 800-772-6436) 

Apremilast 
Summary of Changes CC-10004-PSA-013 
Amgen Inc. 
Amgen Proprietary - Confidential 
Confidential and Proprietary 
2 
    CC-10004-PSA-013 Amendment 4 Final: 03 February 2021 
JUSTIFICATION FOR AMENDMENT 
 
The purpose for this amendment is to better reflect clinical practice and facilitate enrollment.  The 
following changes were made to the protocol, dated 03 February 2021: 
 
Change the primary endpoint to week 16, which is closer to the timeframe in which clinicians 
assess efficacy in clinical practice 
 
Change inclusion criteria 10, a main reason for screen failure, to remove requirement that 
treatment with a maximum of 1 csDMARD (methotrexate or sulfasalazine) begin  6 months 
prior to Baseline to allow for concomitant use of 1 csDMARD if the subject is on a stable 
regimen for at least 3 months prior to the Baseline Visit 
 
Change exclusion criteria 1, another main reason for screen failure, to allow prior use of 
1 csDMARD to treat other conditions like psoriasis other than the study indication (PsA) 
 
Change the early diagnosis period from  3 months and  24 months to  3 months and 
 5 years to be consistent with Study CC-10004-PSA-014, an imaging study on joint impact 
of PsA in the early stages of the disease.  This alignment between studies will ensure a more 
robust clinical and imaging data set in early PsA. 
 
Change timepoints in secondary efficacy endpoints to include Week 16 instead of Week 24 
 
This amendment also includes minor clarifications and corrections to the following sections: 
o 
Section 1.2.1:  Key Findings from Clinical Studies 
o 
Figure 1:  Overall Study Design 
o 
Table 12:  Study Endpoints 
o 
Table 13:  Table of Events 
o 
Section 6.4:  Efficacy Assessments 
o 
Section 6.4.3:  Dactylitis 
o 
Section 6.5.5:  Diarrhea, Nausea and Vomiting 
o 
Section 7.8:  Overdose 
o 
Section 8.1:  Permitted Concomitant Medications and Procedures 
 
Grammatical and typographical changes were made throughout the protocol. 
 

EDMS Doc. Number: 24688746 - 23431284
Apremilast
Summary of Changes CC-10004-PSA-013
Amgen Inc.
Confidential and Proprietary
1
CC-10004-PSA-013 Amendment 3 Final:  04 May 2020
TITLE PAGE
– SUMMARY OF CHANGES –
A PHASE 4, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY TO 
EVALUATE THE EFFICACY AND SAFETY OF APREMILAST (CC-
10004) IN SUBJECTS WITH EARLY, OLIGOARTICULAR 
PSORIATIC ARTHRITIS DESPITE INITIAL STABLE TREATMENT 
WITH EITHER NSAIDS AND/OR ≤ 1 CONVENTIONAL 
SYNTHETIC DMARD
AMENDMENT NO. 3
INVESTIGATIONAL PRODUCT (IP):
Apremilast
PROTOCOL NUMBER:
CC-10004-PSA-013
ORIGINAL DATE:
09 JUL 2018 
AMENDMENT No. 2 DATE:
17 MAY 2019 
AMENDMENT No. 3 DATE:
04 MAY 2020
EudraCT NUMBER:
2018-002735-26
IND NUMBER: 
101761
NCT NUMBER
NCT037479396
Contact Information: 
Name:
, MD
Title:
Medical Director Global Development
Amgen Inc.
Address: 
Amgen Inc,
Amgen Center Dr, Thousand Oaks, CA 91320
USA
Phone:
E-mail:
Note: Only call Amgen Medical Information, if you are not able to reach the Clinical 
Research Physician(s) or Medical Monitor or designee for emergency calls.
Confidentiality Notice
This document contains confidential information of Amgen. This document must not be disclosed to 
anyone other than the site study staff and members of the institutional review board/independent ethics 
committee/institutional scientific review board or equivalent. The information in this document cannot 
be used for any purpose other than the evaluation or conduct of the clinical investigation without the 
prior written consent of Amgen. If you have questions regarding how this document may be used or 
shared, call the Amgen Medical Information number: 1- 800-77-AMGEN
Amgen Medical Information: 1- 800-77-AMGEN (1 800-772-6436)

EDMS Doc. Number: 24688746 - 23431284
Apremilast
Summary of Changes CC-10004-PSA-013
Amgen Inc.
Confidential and Proprietary
2
CC-10004-PSA-013 Amendment 3 Final:  04 May 2020
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
, Vice President and Head of Immunology &Fibrosis Clinical 
Development
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this summary of changes and find its 
content to be acceptable. NOTE: Signed by Celgene based on Approval from 
Amgen Therapeutic Head

EDMS Doc. Number: 24688746 - 23431284
Apremilast
Summary of Changes CC-10004-PSA-013
Amgen Inc.
Confidential and Proprietary
3
CC-10004-PSA-013 Amendment 3 Final:  04 May 2020
JUSTIFICATION FOR AMENDMENT
The purpose of this amendment is to update the change in Sponsor, as well as key contact and 
emergency information, and to update safety reporting and product complaints to align with 
Amgen processes.

All references to “Celgene Corporation” were removed and replaced with “Amgen Inc” 
and “Celgene” changed to “Amgen” throughout the protocol. 

Cover Pages were updated with Amgen contact information.

Section 10 Monitoring and Reporting of Adverse Events was updated to align with 
Amgen Global Drug Safety processes. 

Section 10.4 Pregnancy was modified according to the Amgen Global Drug Safety 
process:
o
Collection of Pregnancy Information and Infant Health Information
o
Collection of information: Male Subjects with Partners Who Become Pregnant 
o
Collection of Lactation Information.

Section 10.5 Reporting of Serious Adverse Events was updated to include instructions for 
paper reporting of SAEs.

Section 12.1 Emergency Contact was updated with Amgen emergency contact 
information..

Section 15.3 Product Complaint Section added.
Additional updates include changes to the following sections:

Section 8.1 Permitted Medications: Correction: “Oral glucocorticosteroids are to be taken on a 
stable dose: prednisone ≤ 10 mg/day (or prednisolone equivalent) for at least 4 weeks prior to the 
Baseline Visit”. The text previous stated “at least 2 weeks prior to the Baseline Visit”. This is 
correctly stated in Inclusion Criteria #8.
The amendment also includes minor clarifications and corrections to align with Amgen 
process:

Section 7.5 Investigational Product Accountability

Section 15.2 Audits and Compliance 

Section 16 Publications. 

EDMS Doc. Number: 23739869 - 23431284
Apremilast
Summary of Changes CC-10004-PSA-013
Celgene Corporation
Confidential and Proprietary
1
CC-10004-PSA-013 Amendment # 2 Final: 17 May 2019
TITLE PAGE
– SUMMARY OF CHANGES –
A PHASE 4, MULTICENTER, RANDOMIZED, DOUBLE-
BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP 
STUDY TO EVALUATE THE EFFICACY AND SAFETY 
OF APREMILAST (CC-10004) IN SUBJECTS WITH 
EARLY, OLIGOARTICULAR PSORIATIC ARTHRITIS 
DESPITE INITIAL STABLE TREATMENT WITH 
EITHER NSAIDS AND/OR ≤ 1 CONVENTIONAL 
SYNTHETIC DMARD
AMENDMENT NO. 2
INVESTIGATIONAL PRODUCT (IP):
Apremilast
PROTOCOL NUMBER:
CC-10004-PSA-013
ORIGINAL DATE:
09 JUL 2018 
AMENDMENT No. 2 DATE:
17 MAY 2019
EudraCT NUMBER:
2018-002735-26
IND NUMBER: 
101761
Contact Information: 
Name:
Title:
Medical Director
Address: 
PPDI
900 Perimeter Park Drive
Morrisville, NC 27560
Phone:
E-mail:
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by 
you, your staff, and ethics committee/institutional review board.  The information contained in this 
document is regarded as confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by law or regulations.  
Persons to whom the information is disclosed must be informed that the information is confidential 
and may not be further disclosed by them.

EDMS Doc. Number: 23739869 - 23431284
Apremilast
Summary of Changes CC-10004-PSA-013
Celgene Corporation
Confidential and Proprietary
2
CC-10004-PSA-013 Amendment # 2 Final: 17 May 2019
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this summary of changes and find its 
content to be acceptable.

EDMS Doc. Number: 23739869 - 23431284
Apremilast
Summary of Changes CC-10004-PSA-013
Celgene Corporation
Confidential and Proprietary
3
CC-10004-PSA-013 Amendment # 2 Final: 17 May 2019
1.
JUSTIFICATION FOR AMENDMENT
Based on comments from Health Authorities, there should be one reference safety information 
(RSI) for a trial. Therefore, Celgene clarifies that the investigator brochure (IB) is the identified
RSI for the trial. 
The IB will be submitted to all sites and clearly identified as the RSI in the clinical trial 
application (CTA) package. 
All references in the protocol that include “approved product labeling” and “Prescribing 
Information” were removed throughout the following sections of the protocol: 

Section 1.2; 

Section 1.2.1.1.1; 

Section 1.2.1.1.2; 

Section 1.2.1.1.3; 

Section 1.2.2.2,

Section 7.1.
Exclusion criteria #2 updated to include prior exposure to tyk2 inhibitors as a prohibited 
medication. 
The amendment also includes several other minor clarifications and corrections:

Section 8.1 Permitted Medications. Intramuscular glucocorticosteroids was deleted.

Section 8.1 Permitted Medications. NSAIDs and/or narcotic analgesics text updated 
for clarity.

Section 8.1 Permitted Medications. Text updated to clarify that only 1 csDMARD is 
allowed during the first 24 weeks of the study. The first 24 weeks of the study was 
added.

Section 8.1 Permitted Medications. Text updated to clarify that after the Week 24 
Visit, changes in therapy will be permitted as clinically required for subjects with 
worsening arthritic symptoms of PsA. The word required was added.

References. Citation for Kruithof was updated with the abbreviated version.

Appendix B CASPAR Criteria. Appendix was replaced with a corrected version of 
the criteria that includes an additional footnote.

EDMS Doc. Number: 23430026 - 23431284
Apremilast
Summary of Changes CC-10004-PSA-013
Celgene Corporation
Confidential and Proprietary
1
CC-10004-PSA-013 Amendment 1 Final: 05 Feb 2019
TITLE PAGE
– SUMMARY OF CHANGES –
A PHASE 4, MULTICENTER, RANDOMIZED, DOUBLE-
BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP 
STUDY TO EVALUATE THE EFFICACY AND SAFETY 
OF APREMILAST (CC-10004) IN SUBJECTS WITH 
EARLY, OLIGOARTICULAR PSORIATIC ARTHRITIS 
DESPITE INITIAL STABLE TREATMENT WITH 
EITHER NSAIDS AND/OR ≤ 1 CONVENTIONAL 
SYNTHETIC DMARD
AMENDMENT NO. 1
INVESTIGATIONAL PRODUCT (IP):
Apremilast 
PROTOCOL NUMBER:
CC-10004-PSA-013
ORIGINAL DATE:
09 JUL 2018
AMENDMENT No. 1 DATE:
05 FEB 2019
EudraCT NUMBER:
2018-002735-26
IND NUMBER: 
101761
Contact Information: 
Name:
Title:
Medical Director
Address: 
PPDI
900 Perimeter Park Drive
Morrisville, NC 27560
Phone:
E-mail:
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by you, 
your staff, and ethics committee/institutional review board.  The information contained in this document is 
regarded as confidential and, except to the extent necessary to obtain informed consent, may not be 
disclosed to another party unless such disclosure is required by law or regulations.  Persons to whom the 
information is disclosed must be informed that the information is confidential and may not be further 
disclosed by them.

EDMS Doc. Number: 23430026 - 23431284
Apremilast
Summary of Changes CC-10004-PSA-013
Celgene Corporation
Confidential and Proprietary
2
CC-10004-PSA-013 Amendment 1 Final: 05 Feb 2019
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
{See appended electronic signature page}
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this summary of changes and find its 
content to be acceptable.

EDMS Doc. Number: 23430026 - 23431284
Apremilast
Summary of Changes CC-10004-PSA-013
Celgene Corporation
Confidential and Proprietary
3
CC-10004-PSA-013 Amendment 1 Final: 05 Feb 2019
1.
JUSTIFICATION FOR AMENDMENT
Significant changes noted below were made based on Health Authority comments and to align 
with the approved label for apremilast:

Section 4.3 Exclusion Criteria; Clarification of Exclusion #8 and addition of Exclusion 
#9 (laboratory abnormalities) modified to add severe renal disease as a significant 
laboratory abnormality.

Section 6.5.7 Clinical Laboratory Evaluations; Creatinine clearance added to support 
Exclusion Criteria #9.

Section 6.5.2: Vital Signs, Height and Weight; Section modified to clarify treatment 
discontinuation for severe weight loss. Weight will be added to every visit. The following 
sections were also revised:
o
Section 5 Table of Events; Weight assessment increased to be done at every visit
to support modification of Section 6.5.2.
o
Section 6.3.1 Safety Follow-up Period; Weight added.

Section 6.5.4: Psychiatric Evaluation; Section was modified to clarify study
discontinuation for psychiatric symptoms.

Section 6.5.5: Diarrhea, Nausea and Vomiting; Section was added to clarify treatment 
discontinuation for severe symptoms of diarrhea, nausea and vomiting.

Section 8.2 Concomitant Medications Not Recommended; Section added to align with 
guidance provided in the label regarding co-administration of strong cytochrome P450 
3A4 enzyme inducers with apremilast.
Significant changes noted below were made based on Health Authority comments:

Section 4.2 Inclusion Criteria #13; Updated to clarify that contraception, Option 2, may 
not be acceptable as a highly effective contraception option in all countries per local 
guidelines/regulations.

Section 6.5.1 Serum and Urine Pregnancy Tests for Females of Childbearing Potential; 
Section modified to clarify that additional visits (unscheduled visits) may be done to 
monitor pregnancy testing.
The amendment also includes several other minor clarifications and corrections:

Medical Monitor / Emergency Contact Information; Updated with the PPD Medical 
Monitor names.

The protocol was modified to update the International Conference on Harmonization with
International Council for Harmonisation.

Section 1.2 Compound Background; As this is a Phase 4 study, approved product 
labeling or the Investigator brochure (depending on regional regulations) should be used 
as the reference for additional information on apremilast in this approved indication.

EDMS Doc. Number: 23430026 - 23431284
Apremilast
Summary of Changes CC-10004-PSA-013
Celgene Corporation
Confidential and Proprietary
4
CC-10004-PSA-013 Amendment 1 Final: 05 Feb 2019

Section 4.2 Inclusion Criteria #11; Clarification to the wording of discontinuation criteria 
for sulfasalazine and methotrexate. Also, update was made in Section 8.1 Permitted 
Concomitant Medications and Procedures.

Section 4.3 Exclusion Criteria #3; Intra-muscular glucocorticosteroids added. Also,
updates were made in Section 8.1 Permitted Concomitant Medications and Section 8.3 
Prohibited Concomitant Medications and Procedures.

Section 6.5.7 Clinical Laboratory Evaluations; “dipstick urinalysis” was deleted to align 
with the Laboratory Manual. The updates were also made in Section 6 Procedures: 
(Sections 6.1, 6.2, 6.2.1) and Table 13.

Section 6.1 Screening Period Demographics; Date of birth deleted to align with current 
clinical database.

Section 10 Adverse Events; Updated with the revised language for electronic data capture 
of safety data (“Safety Gateway”).

Appendix N PSA Impact of Disease 12-Item (PsAID-12) Questionnaire; Calculations and 
Section 9 updated per statistician’s request.

Appendix T Blister Card Configuration; Treatment cards replaced with the corrected 
image.