Clinical trial NCT04800315
Conditions: Dermatitis, Atopic Eczema
Keywords: Atopic Dermatitis Cendakimab CC-93538
Sponsor: Celgene
Start date: 2021-05-14; Completion date: 2022-11-09
Enrollment: 221 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the effectiveness and safety of 3 dose regimen of CC-93538 in adult participants with moderate to severe Atopic Dermatitis (AD).

Detailed description:

Arms: arm 1: Administration of CC-93538 Subcutaneous (SC) Once weekly (QW) for 16 weeks. arm 2: Starting at the baseline visit, active IP will be administered. On the alternate weeks, placebo will be administered to maintain the blind. arm 3: Starting at the baseline visit, active IP and matching placebo will be administered.

On the alternate weeks, placebo will be administered weekly to maintain the blind. arm 4: Administration of placebo each week.
Interventions: intervention 1: CC-93538 intervention 2: Placebo
Intervention descriptions: intervention 1: Specified dosages on specified days intervention 2: Specified dosages on specified days

Protocol documents:
Prot_SAP_000.pdf: 
Protocol for 
 
Official Title of Study 
A PHASE 2, MULTICENTER, GLOBAL, RANDOMIZED, 
DOUBLE-BLIND, PLACEBO-CONTROLLED, 
PARALLEL-GROUP STUDY TO EVALUATE THE 
SAFETY AND EFFICACY OF CENDAKIMAB (CC-93538) 
IN ADULT SUBJECTS WITH MODERATE TO SEVERE 
ATOPIC DERMATITIS 
NCT04800315 
January  13, 2021 


EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
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Protocol CC-93538-AD-001 Final: 13 Jan 2021
 
A PHASE 2, MULTICENTER, GLOBAL, RANDOMIZED, 
DOUBLE-BLIND, PLACEBO-CONTROLLED, 
PARALLEL-GROUP STUDY TO EVALUATE THE 
SAFETY AND EFFICACY OF CENDAKIMAB (CC-93538) 
IN ADULT SUBJECTS WITH MODERATE TO SEVERE 
ATOPIC DERMATITIS
PROTOCOL NUMBER:
CC-93538-AD-001 
DATE FINAL:
13 Jan 2021
EudraCT NUMBER:
2020-005212-22
IND NUMBER:
154623
SPONSOR NAME/ ADDRESS:
Celgene International II Sàrl
Rue du Pré-Jorat 14
2108 Couvet 
Switzerland 
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.
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Cendakimab (CC-93538)
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Celgene International II Sàrl
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MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION 
Contact Information:
Name:
Title:
Address: 86 Morris Avenue, Summit, NJ 07901
Phone:
E-mail:
Note: The back-up 24-hour global emergency contact call center should only be used if 
you are not able to reach the Clinical Research Physician(s) or Medical Monitor or 
designee for emergency calls.
Back-up 24-hour Global Emergency Contact Call Center: 
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SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Site Principal Investigator
dd mmm yyyy
Printed Name of Site Principal Investigator
Institution Name:_______________________________________
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 
Celgene 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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COORDINATING PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Coordinating Principal Investigator
dd mmm yyyy
Printed Name of Coordinating Principal Investigator
Institution Name:_______________________________________
By my signature, I agree the protocol has been written to comply with ICH Good 
Clinical Practices guidelines and agree to offer guidance throughout the study as 
needed.
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
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PROTOCOL SUMMARY
Study Title
A Phase 2, Multicenter, Global, Randomized, Double-blind, Placebo-controlled, Parallel-group 
Study to Evaluate the Safety and Efficacy of Cendakimab (CC-93538) in Adult Subjects with 
Moderate to Severe Atopic Dermatitis.
Indication
CC-93538 is a recombinant humanized, high-affinity neutralizing (immunoglobulin G1 kappa 
[IgG1κ]) monoclonal antibody (mAb) selective for interleukin-13 (IL-13). CC-93538 binds to 
IL-13, thus preventing its interaction with both IL-13 receptors, IL-13 receptor alpha 1 (IL-
13Rα1) and IL-13 receptor alpha 2 (IL-13Rα2). Atopic dermatitis (AD) is a common and chronic 
type 2 immunity driven inflammatory skin disorder. Type 2 cytokines have a strong impact on 
the skin immune response and barrier function.  Interleukin-4 (IL-4) and IL-13 are both key 
cytokines involved in type 2 inflammatory conditions; however, evidence continues to emerge 
that supports IL-13 as a primary cytokine involved in AD (Bieber, 2019).  The assumed central
role of IL-13 in allergic and type 2 inflammatory conditions strengthens the position for CC-
93538 as a potential treatment option for patients with moderate to severe AD.
Objectives
Primary Objective

To evaluate the clinical efficacy of 3 dosage regimens of CC-93538 [(
mg once 
weekly (QW), 
mg every other week (Q2W), and 
 mg (Q2W)], compared with 
placebo on the change in the core clinical outcome measure, Eczema Area and 
Severity Index (EASI), in subjects with moderate to severe AD
Secondary Objective

To evaluate the effect of 3 CC-93538 dosage regimens, compared with placebo on 
additional clinical outcome measures and patient reported outcomes in subjects with 
moderate to severe AD

To evaluate the safety and tolerability, including characterization of the 
immunogenicity profile of 3 dosing regimens of CC-93538, compared with placebo in 
subjects with moderate to severe AD

To assess the trough serum concentration of CC-93538 in subjects with moderate to 
severe AD
Study Design
This is a global, multicenter, randomized, double-blind, placebo-controlled, 4 arm, parallel-
group, dose-ranging, Phase 2 study to evaluate the efficacy and safety of CC-93538 in 
approximately 200 adult subjects with moderate to severe AD.  Subjects participating in the 
study must be candidates for systemic therapy, defined as having an intolerance or inadequate 
response to treatment with topical medications for at least 4 weeks, or who have required at least 
1 systemic therapy to control their disease.  
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
Clinically significant changes in vital signs, physical examinations, and laboratory 
findings.

Ongoing safety surveillance of AE/serious adverse events (SAEs) related to COVID-
19

Presence of and clinical effects of anti-drug antibodies (ADAs)
Statistical Methods
Sample Size Determination 
Approximately 200 subjects will be randomized in this Phase 2 dose ranging study. 
Randomization will be equal among the 4 dose groups of placebo, 
 mg Q2W, 
mg Q2W, 
and 
 mg QW (approximately 50 subjects per group). Assuming a 10% dropout rate, a sample 
size of 45 subjects per group will provide approximately 90% power to detect a treatment 
difference relative to placebo (difference in means) of 35% with respect to the primary endpoint 
of percentage change from baseline in EASI scores at Week 16.
The sample size calculations are based on the following considerations for comparing mean 
percentage changes from baseline in EASI scores at Week 16 versus placebo. In particular, the 
recent Phase 2b study of dupilumab trial reported an observed mean for placebo of 18.1% and 
corresponding treatment differences of 50.1% (standard error [SE] = 6.7% ) and 55.7% (SE =
6.7%), for the doses of 300 mg Q2W, and 300 mg QW, respectively (Thaçi, 2016). 
This study evaluating CC-93538 is designed to detect a (true) treatment difference relative to 
placebo of 35%.  We assume a (true) mean of 20% for placebo, and means for the active dose 
groups corresponding to treatment differences of 25% (
mg Q2W), 30% (
mg Q2W), and 
35% (
 mg QW), with a common standard deviation (SD) of 50%. We note that the common 
SD assumption of 50% for the percentage change from baseline in EASI scores at Week 16 was 
also assumed in the dupilumab Phase 2b study design (Thaçi, 2016). Under these assumptions, it
is estimated that with a sample size of 45 subjects per group the study provides approximately 
90% power to detect superiority relative to placebo for at least 1 dose at the overall type-1 error 
of α = 0.05 (two-sided) using a hierarchical testing approach (in the order of 
mg QW versus
placebo,
 mg Q2W versus placebo, and 
mg Q2W versus placebo). 
Statistical Analysis 
Primary Efficacy Endpoint
The primary efficacy endpoint of percentage change from baseline in EASI scores at Week 16 
will be analyzed using an analysis of covariance(ANCOVA) model, based on the modified intent 
to treat (mITT) population, with treatment group indicators as the main effects adjusting for 
baseline EASI scores, and the stratification factors of vIGA-AD score (3[moderate] or 4 
[severe]) and region (Japan versus rest of the world [RoW]) as covariates. For each of the active 
treatment arms, the adjusted mean percentage changes from baseline and corresponding 
differences versus placebo in EASI scores at Week 16 will be estimated (based on Least-Squares 
Means) along with 95% Wald confidence intervals (CIs) and p-values.
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To adjust for multiplicity (with respect to the 3 active doses), a standard hierarchical approach 
will be utilized by conducting comparisons, each at the 2-sided 0.05 alpha-level (based on the 
aforementioned adjusted p-values), in the order of 
mg QW versus placebo, 
 mg Q2W 
versus placebo, and 
 mg Q2W versus placebo.
Key Secondary Endpoints
There are 2 key secondary endpoints: (1) proportion of subjects with both an vIGA-AD score of 
0 (clear) or 1 (almost clear) and a reduction ≥ 2 points in vIGA-AD score from Baseline at Week 
16; and (2) proportion of subjects with at least a 75% improvement from baseline in Eczema 
Area and Severity Index (EASI-75) at Week 16.  These endpoints will be analyzed using a 
stratified Cochran-Mantel-Haenszel (CMH) test at a two-sided 5% significance level.  
The randomization stratification levels are: 

Japan region, 

RoW region and vIGA-AD score 3, and 

RoW region and vIGA-AD score 4
Differences in proportions versus placebo and associated 95% confidence intervals will also be 
provided along with p-values.
The hierarchical testing approach used for the primary endpoint will be utilized to adjust for 
multiplicity with respect to the 3 active doses for each of these key secondary endpoints.  
However, multiplicity adjustments are not implemented across the primary and 2 key secondary 
endpoints simultaneously.
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TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
PROTOCOL SUMMARY ..........................................................................................................7
1.
INTRODUCTION..................................................................................................19
1.1.
Disease Background ...............................................................................................19
1.2.
Compound Background ..........................................................................................20
1.2.1.
Mechanism of Action .............................................................................................20
1.2.2.
Clinical Studies.......................................................................................................21
1.2.2.1.
.21
1.2.2.2.
.22
1.2.2.3.
.22
1.2.2.4.
22
1.3.
Rationale ................................................................................................................24
1.3.1.
Study Rationale and Purpose ..................................................................................24
1.3.1.1.
Benefit-Risk Assessment ........................................................................................26
1.3.2.
Rationale for the Study Design ...............................................................................27
1.3.3.
Rationale for Dose, Schedule and Regimen Selection .............................................28
1.3.4.
Rationale for Choice of Comparator Compounds....................................................29
1.3.5.
Rationale for Pharmacodynamics and Potential Predictive Biomarkers ...................29
2.
STUDY OBJECTIVES AND ENDPOINTS...........................................................30
3.
OVERALL STUDY DESIGN ................................................................................34
3.1.
Study Design ..........................................................................................................34
3.2.
Study Duration for Subjects....................................................................................35
3.3.
End of Trial ............................................................................................................36
4.
STUDY POPULATION.........................................................................................37
4.1.
Number of Subjects ................................................................................................37
4.2.
Inclusion Criteria....................................................................................................37
4.3.
Exclusion Criteria...................................................................................................39
5.
TABLE OF EVENTS.............................................................................................41
6.
PROCEDURES......................................................................................................49
6.1.
Screening Period.....................................................................................................49
6.1.1.
Additional Information Regarding Safety Laboratory Assessments.........................52
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6.1.2.
Screening Failures and Rescreening of Potential Subjects.......................................52
6.1.3.
Rescreening of subjects who develop COVID-19 during the Screening 
Period.....................................................................................................................52
6.2.
Treatment Period ....................................................................................................53
6.2.1.
End of Treatment or Early Termination ..................................................................54
6.3.
Follow-up Period....................................................................................................55
6.3.1.
Safety Follow-up (Initial [Week 24]and Final [Week 32]) ......................................55
6.4.
Efficacy Assessments .............................................................................................55
6.4.1.
Validated Investigator Global Assessment ..............................................................55
6.4.2.
Eczema Area and Severity Index ............................................................................55
6.4.3.
Body Surface Area..................................................................................................56
6.4.4.
SCORing Atopic Dermatitis Index..........................................................................56
6.5.
Subject Reported Efficacy Assessments and Outcome Measures.............................56
6.5.1.
Pruritus Numeric Rating Scale................................................................................56
6.5.2.
PROMIS Sleep Disturbance Short Form.................................................................57
6.5.3.
Patient Oriented Eczema Measure...........................................................................57
6.5.4.
Dermatology Quality of Life Index.........................................................................57
6.5.5.
Hospital Anxiety and Depression Scale (HADS).....................................................57
6.6.
Safety Assessments.................................................................................................57
6.6.1.
Onsite Visit Frequency ...........................................................................................58
6.6.2.
Blinded Safety Data Reviews..................................................................................58
6.6.3.
Internal Safety Management Team..........................................................................58
6.6.4.
Data Monitoring Committee Safety Oversight ........................................................59
6.7.
Anti-drug Antibody Assessments............................................................................59
6.8.
Subject Reported Outcomes....................................................................................59
6.9.
Pharmacokinetics....................................................................................................59
6.10.
Biomarkers, Pharmacodynamics, Pharmacogenomics.............................................60
6.10.1.
Whole Blood and Serum Biomarker Assessments...................................................60
6.10.2.
Tissue Biomarker Assessments...............................................................................60
6.11.
Additional and Optional Research...........................................................................60
6.11.1.
Additional Research ...............................................................................................61
6.11.2.
Optional Research ..................................................................................................61
7.
DESCRIPTION OF STUDY TREATMENTS........................................................62
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7.1.
Description of Investigational Product(s)................................................................62
7.2.
Treatment Administration and Schedule .................................................................62
7.2.1.
Administration by a Visiting Home Health Care Provider.......................................63
7.2.2.
Missed Dose(s).......................................................................................................63
7.2.3.
Overdose ................................................................................................................63
7.2.4.
Dose Adjustments...................................................................................................64
7.2.5.
Guidelines for Temporary Interruption of Dosing ...................................................64
7.2.6.
Criteria for Discontinuation of Dosing ....................................................................65
7.3.
Method of Treatment Assignment...........................................................................66
7.4.
Packaging and Labeling..........................................................................................67
7.5.
Investigational Product Accountability and Disposal ..............................................67
7.6.
Investigational Product Compliance........................................................................67
8.
CONCOMITANT MEDICATIONS AND PROCEDURES....................................69
8.1.
Permitted Concomitant Medications and Procedures...............................................69
8.2.
Prohibited Concomitant Medications and Procedures..............................................69
8.3.
Required Concomitant Medications and Procedures................................................70
8.4.
Rescue Medication .................................................................................................71
9.
STATISTICAL CONSIDERATIONS ....................................................................72
9.1.
Overview................................................................................................................72
9.2.
Study Population Definitions ..................................................................................72
9.3.
Sample Size and Power Considerations...................................................................72
9.4.
Background and Demographic Characteristics........................................................73
9.5.
Subject Disposition.................................................................................................73
9.6.
Efficacy Analysis....................................................................................................74
9.6.1.
Efficacy Analysis of the Primary Endpoint .............................................................74
9.6.1.1.
Percentage Change from Baseline in EASI Scores at Week 16................................74
9.6.1.2.
Subgroup Analysis of Primary Endpoint.................................................................74
9.6.2.
Efficacy Analysis of Secondary Endpoints..............................................................75
9.6.2.1.
Analysis Methods ...................................................................................................75
9.7.
Safety Analysis.......................................................................................................76
9.8.
Interim Analysis .....................................................................................................76
9.9.
Other Topics...........................................................................................................76
9.9.1.
Analysis of Exploratory Endpoints .........................................................................76
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9.9.3.
Data Monitoring Committee ...................................................................................77
10.
ADVERSE EVENTS..............................................................................................78
10.1.
Monitoring, Recording and Reporting of Adverse Events .......................................78
10.2.
Evaluation of Adverse Events.................................................................................78
10.2.1.
Seriousness.............................................................................................................78
10.2.2.
Severity/Intensity....................................................................................................79
10.2.3.
Causality ................................................................................................................80
10.2.4.
Duration .................................................................................................................80
10.2.5.
Action Taken..........................................................................................................80
10.2.6.
Outcome.................................................................................................................81
10.3.
Abnormal Laboratory Values..................................................................................81
10.4.
Pregnancy...............................................................................................................81
10.4.1.
Females of Childbearing Potential ..........................................................................81
10.5.
Reporting of Serious Adverse Events......................................................................82
10.6.
Adverse Events of Special Interest..........................................................................82
10.7.
Expedited Reporting of Adverse Events..................................................................83
11.
DISCONTINUATIONS .........................................................................................84
11.1.
Treatment Discontinuation......................................................................................84
11.2.
Study Discontinuation ............................................................................................84
11.3.
Emergency Contact.................................................................................................85
11.4.
Emergency Identification of Investigational Products .............................................85
12.
REGULATORY CONSIDERATIONS...................................................................86
12.1.
Good Clinical Practice............................................................................................86
12.2.
Investigator Responsibilities ...................................................................................86
12.3.
Subject Information and Informed Consent.............................................................87
12.4.
Confidentiality........................................................................................................87
12.5.
Protocol Amendments.............................................................................................87
12.6.
Institutional Review Board/Independent Ethics Committee Review and 
Approval ................................................................................................................87
12.7.
Ongoing Information for Institutional Review Board/ Ethics Committee ................88
12.8.
Termination of the Study ........................................................................................88
13.
DATA HANDLING AND RECORDKEEPING.....................................................89
13.1.
Data/Documents .....................................................................................................89
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13.2.
Data Management...................................................................................................89
13.3.
Record Retention....................................................................................................89
14.
QUALITY CONTROL AND QUALITY ASSURANCE........................................91
14.1.
Study Monitoring and Source Data Verification......................................................91
14.2.
Audits and Inspections............................................................................................91
14.3.
Investigational Medicinal Product Quality Issues....................................................91
15.
PUBLICATIONS ...................................................................................................93
16.
REFERENCES.......................................................................................................94
APPENDIX A.
TABLE OF ABBREVIATIONS....................................................................98
APPENDIX B.
HANIFIN/RAJKA DIAGNOSTIC CRITERIA FOR ATOPIC 
DERMATITIS......................................................................................................103
APPENDIX C.
VALIDATED INVESTIGATOR GLOBAL ASSESSMENT SCALE 
FOR ATOPIC DERMATITIS (V-IGA™) .............................................................104
APPENDIX D.
ECZEMA AREA AND SEVERITY INDEX (EASI)...................................105
APPENDIX E.
BODY SURFACE AREA............................................................................107
APPENDIX F.
SCORING ATOPIC DERMATITIS INDEX................................................108
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LIST OF TABLES
Table 1:
Study Objectives.....................................................................................................30
Table 2:
Study Endpoints .....................................................................................................31
Table 3:
Screening Visit Procedures.....................................................................................41
Table 4:
Treatment Period Procedures..................................................................................44
Table 5:
Follow Up Period Procedures .................................................................................47
Table 6:
Abbreviations and Specialist Terms........................................................................98
Table 7:
Handprint Assessment of BSA..............................................................................107
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LIST OF FIGURES
Figure 1:
Overall Study Design..............................................................................................35
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1.
INTRODUCTION 
1.1.
Disease Background 
Atopic dermatitis (AD) is a common and chronic inflammatory skin disorder that affects a broad 
demographic, with an increasing prevalence worldwide. Although reported prevalence rates of 
AD vary, it is estimated that AD affects between 3% to 10% of the United States (US)
population, and worldwide, AD affects up to 20% of children and 3% of adults (Sacotte, 2018). 
Of those affected, about 40% have moderate to severe disease, consistent with high disease 
burden, resulting in a significant impact on a patient’s quality of life (Chiesa, 2019). Atopic 
dermatitis is associated with increased anxiety, depression, sleep disorders, reduced productivity, 
and impaired activity, all of approximately equivalent magnitude to those observed in psoriasis
(Eckert, 2017).  In addition, patients with AD have increased risk of other atopic disorders, 
including asthma, allergic rhinitis, and chronic sinusitis with nasal polyposis (Chandra, 2011; 
Mallol, 2013; Schneider, 2013) highlighting the need for more advanced therapies and treatment 
options within this evolving field. A recent study performed in the United States focused on the 
costs and treatment patterns associated with more advanced therapies such as dupilumab (anti-
interleukin 4 receptor [IL-4R] monoclonal antibody), systemic corticosteroids, systemic 
immunosuppressants, and phototherapy.  This study estimated that almost two-thirds of patients 
with moderate to severe AD who initiated systemic immunosuppressants, and a quarter of those 
who initiated dupilumab, discontinued treatment within 6 months. These patients represent a 
significant burden to the healthcare system, with costs in the United States representing 
approximately $20,000 per patient per year (Eichenfield, 2020).  As such, there remains a clear 
unmet need for additional advancements in treatment options to address the complex medical 
and societal needs of patients with moderate to severe AD.
A multiplicity of factors, including epidermal barrier defects, dysregulation of innate immune 
responses, and altered type 2 immunity, are implicated in the pathogenesis of AD, culminating in 
a series of complex inflammatory responses involving multiple cell types, cytokines and 
chemokines.  Enhanced allergen/antigen penetration through an impaired skin barrier resulting in 
a type 2 T helper (Th2)-type milieu has been proposed as a critical link between the primary 
barrier defect in patients with AD and Th2 polarization (Boguniewicz, 2011).  Type 2 T helper
differentiation of naive CD4+ T cells predominates in AD, causing an increased production of 
interleukins (IL), primarily interleukin-4 (IL- 4), interleukin-5 (IL-5), and interleukin-13 (IL-13), 
which then leads to an increased level of immunoglobulin E (IgE) (Alexander, 2019).  IL- 4 and 
IL-13are both key cytokines involved in type 2 inflammatory conditions; however, evidence 
continues to emerge that supports IL-13 as a primary cytokine involved in AD. (Bieber, 2019). 
Until recently, treatment for moderate or severe AD involved hydration of the skin, and/or 
application of topical treatments such as corticosteroids, calcineurin inhibitors, nonsteroidal 
phosphodiesterase 4 inhibitors, tar, vitamin D, or dilute bleach.  First line therapy for moderate to 
severe AD is treatment with topical corticosteroids (TCS). Topical calcineurin inhibitors (TCI), 
are typically used as second line therapy, or as an alternative therapy for patients with TCS 
intolerance. Although topical therapies remain a mainstay in the treatment in AD, these 
treatments continue to be associated with limited efficacy. In addition, long-term application of 
TCS carries the risk of side-effects, such as acneiform eruptions, dyspigmentation, skin atrophy, 
and risks associated with systemic absorption (Sidbury, 2014). 
Approved
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Approved
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Approved
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Approved
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Approved
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
23
Protocol CC-93538-AD-001 Final: 13 Jan 2021
Subjects were randomized to receive either CC-93538 180 mg (N = 31), CC-93538 360 mg (N = 
34), or placebo (N = 34) weekly for 16 weeks during the double-blind (DB) Treatment Period.  
On the first day of dosing subjects received an IV load of either CC-93538 (5 mg/kg or 10 
mg/kg) or placebo prior to SC dosing.  An optional Open-Label Extension (OLE) for an 
additional 52 weeks where all subjects received 360 mg CC-93538 SC weekly was available for 
subjects completing the DB Treatment Period.  Of the 99 subjects randomized and dosed, 86
entered the OLE and 66 subjects completed Week 52 of the OLE.
In Study RPC02-201, the primary endpoint (changes in esophageal eosinophil count at Week 16) 
was met. CC-93538 also improved inflammatory features of EoE including the endoscopic 
appearance of the esophageal mucosa and improvements in histologic changes including fibrosis 
parameters characteristic of EoE.  Mean reductions in the subject’s and clinician’s global 
assessment of disease severity score were significant with the 360 mg dose.
Long-term treatment with CC-93538 360 mg showed sustained improvements in esophageal 
eosinophil count and other inflammatory features of EoE at Week 68.  In the OLE, the treatment 
of subjects with weekly CC-93538 360 mg SC doses demonstrated continued improvement in 
subjects who transitioned from placebo and those who originally received the CC-93538 180 mg 
or 360 mg dose in the DB Treatment Period of the study.  
Results from the Phase 2 Study, RPC02-201, suggest that CC-93538 at doses of 180 mg and 360 
mg weekly was well tolerated and had an acceptable safety profile in subjects with EoE.  The 
most frequently occurring related TEAEs (> 5% in the total CC-93538 group) in the DB
Treatment Period, shown with incidences in the placebo, CC-93538 180 mg, and CC-93538 360
mg groups, respectively, were upper respiratory tract infection (2.9%, 9.7%, 11.8%), headache
(8.8%, 9.7%, 8.8%), and arthralgia (0%, 12.9%, 2.9%). Injection site reaction TEAEs, were
reported for 17.6% of placebo subjects, 12.9% subjects in the 180 mg CC-93538 group, and 
26.5% of subjects in CC-93538 360 mg group. The most frequently occurring TEAEs in the 
OLE assessed as at least possibly related to study drug (> 3%) were headache and injection site
hematoma (4.7% each), and injection site erythema, nasopharyngitis, and upper respiratory tract
infection (3.5% each). Injection site reaction TEAEs were reported for 18.6% of subjects in the
OLE Population. Anti-drug antibodies were assessed throughout the DB and OLE periods of the
study and were not associated with any safety findings.  
No deaths were reported throughout the study (inclusive of DB and OLE periods). Three subjects 
experienced 1 SAE each in the DB Treatment Period, including 2 subjects in the placebo group 
(1 with appendicitis and 1 with umbilical hernia, both moderate) and 1 subject in the CC-93538 
360 mg group (severe appendicitis). All SAEs in the DB Treatment Period were assessed as 
unrelated to study drug. Six subjects experienced 1 SAE each in the OLE, of which 2 had severe, 
possibly related events (cholecystitis acute and abortion spontaneous) and 4 had unrelated or 
unlikely related events (moderate asthma, diverticulitis with perforation, schizophrenia, and 
femur fracture due to motorcycle accident). 
Mean CC-93538 serum trough concentration (Ctrough) values for subjects in the 360 mg dose 
group were approximately 2-fold of mean CC-93538 Ctrough values for subjects in the 180 mg 
dose group at each visit, suggesting a dose-proportional increase in exposure.  During the OLE, 
mean CC-93538 Ctrough values were similar across double-blind randomized treatment groups by 
OLE at Week 12, with these levels sustained through OLE at Week 52.  
Approved
4.0
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Approved
1.0
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab(CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
24
Protocol CC-93538-AD-001 Final:13 Jan 2021
CC 93538 trough concentration data showed steady state was reached between Weeks 12 and 16 
of dosing, consistent with the t
½.
These Phase 2 data indicate that targeting IL-13 with CC-93538 significantly improves many of 
the important disease and symptomatic features of EoE and is well tolerated.  The data support 
the further study of CC-93538 as a novel treatment for EoE, and a Phase 3 program is planned to 
be initiated in the first half of 2021.
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).
1.3.
Rationale
1.3.1.
Study Rationale and Purpose
Continuous advances have been made in understanding AD pathophysiology over the years.  
Evidence continues to emerge that supports IL13 as a primary cytokine involved in AD, 
including its central role in the generation and maintenance of the inflammatory reaction and 
epidermal barrier function. (Bieber, 2019).  The frequency of type 2 (IL-13+) T cells is 
significantly increased in lesional AD skin compared to both healthy and non-lesional AD skin.
ThisIL-13 signals via the IL-13 receptor, through theheterodimer of IL-13Rα1 and IL-4Rαon 
multiple cells types including fibroblasts, pericytes, and vascular smooth muscle cells in the AD 
skin (He, 2020).Moreover, biologic therapiesspecificallytargeting IL-13, such as lebrikizumab
and tralokinumab, havedemonstrated potential therapeutic benefit, and an acceptable safety 
profilein subjects with moderate to severe AD.  
Tralokinumab is an anti-IL-13 mAb that has similar binding properties to CC-93538. 
Tralokinumab binds to the IL-13 cytokine at an epitope that overlaps with the binding site of the 
IL13Rα receptor, preventing IL-13 from binding to both IL-13Rα1 and IL-13Rα2 (Popovic, 
2017).  Positive results were generated from 3pivotal Phase 3 studies (ECZTRA 1, 2 and 
ECZTRA 3) evaluating tralokinumab in subjects with moderate to severe AD. Recent acceptance 
of the EU Marketing Authorisation Application (MAA) and US Biologics License Application 
(BLA) for tralokinumab in the treatment of adults with moderate-to-severe AD further validates 
the potential therapeutic benefit of IL-13 in this disease.  
Tralokinumab when dosed at 300mg every other week (Q2W)demonstrated superiority over 
placeboin all primary and secondary endpoints at Week 16.  For the primary endpoint, an IGA 
0/1 was achieved for subjects treated with tralokinumab was 15.8% for versus 7.1% for placebo 
in ECZTRA 1 and 22.2% versus 10.9% for ECZTRA 2. Reduction of theworst dailyaverage of 
Pruritus Numeric Rating Scale (NRS)≥ 4from baseline to Week 16 was 20·0% with 
tralokinumab versus 10·3% with placebo in ECZTRA 1 and by 25·0% versus 9·5% with placebo 
in ECZTRA 2.  The overall frequency and severity of AEs over 16 weeks was comparable 
between tralokinumab and placebo. Of the most frequently reported AEs (≥5% inany treatment 
group), upper respiratory tract infectionandconjunctivitis occurred more frequently with 
tralokinumab versus placebo, and dermatitis atopic andskin infection occurred more frequently 
with placebo(Wollenberg, 2020
Approved 4.0
v
).  Tralokinumab demonstratedinPhase 3 studies that targeting 
IL-13 alone in isboth a safe and effective therapy; however,is theoverallefficacy profile does 
not appear to be superior to biologic agents already on the market.  When compared to the results 
Approved 1.0
v


EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
25
Protocol CC-93538-AD-001 Final: 13 Jan 2021
reported from dupilumab Phase 3 SOLO 1 and SOLO 2 induction studies, response rates for
achieving IGA 0/1were as high as 38% to 36% in the dupilumab 300 mg Q2W arm, compared to 
10% to 8% in subjects treated with placebo (Simpson, 2016).  Although tralokinumab is 
anticipated to the first anti-IL-13 approved for the treatment of moderate to severe AD, there
remains a need to further evaluate other biologic agents targeting IL-13 pathway, to further 
assess anti-IL-13’s potential of achieving an optimized efficacy profile in subjects with moderate 
to severe AD.
Lebrikizumab is an anti-IL-13 mAb, with a different mechanism of action (MOA) than 
tralokinumab, as it selectively targets IL-13 and prevents formation of the IL-13Rα1/IL-4Rα 
heterodimer receptor signaling complex (Ultsch, 2013).  In recently published data from the 
Phase 2b study, lebrikizumab demonstrated efficacy across all key clinical outcome measures
(eg, IGA, and EASI scores) in subjects with moderate to severe AD, particularly at the highest 
dose level evaluated (eg, loading doses of 500 mg at baseline and week 2, followed by 250 mg of 
lebrikizumab administered every other week for a total of 16 weeks).  Robust efficacy was 
observed with lebrikizumab treatment on pruritus, with improvement in Pruritus NRS score of 
≥4 points from baseline in 70% of subjects on treatment compared with 27.3 % of subjects on 
placebo at Week 16.  In addition, changes of at least 4 points in the Pruritus NRS score were 
seen as early as Day 2 in 15.3% [9 of 59] subjects treated with lebrikizumab at the highest dose 
level, as compared to 4.5% [2 of 44] subjects treated with placebo. These promising clinical 
observations associated with itch reduction in subjects treated with lebrikizumab support the 
preclinical evidence that IL-13 directly sensitizes sensory neurons to respond to pruritogens 
(Miron 2018).  In addition to the enhanced efficacy profile demonstrated by the Phase 2 results, 
lebrikizumab was generally well tolerated, and had a favorable safety profile consistent with 
previous lebrikizumab studies conducted in AD and the extensive asthma Phase 2b and Phase 3 
programs which enrolled over 1000 subjects (Hanania, 2016, Korenblat, 2018).  Common 
TEAEs (≥5% in any lebrikizumab group) included upper respiratory tract infection, 
nasopharyngitis, headache, injection site pain, and fatigue.  Serious TEAEs including peripheral 
edema, chronic obstructive pulmonary disease, and pulmonary embolism were reported by 2 of 
52 placebo subjects (3.8%) and by 4 of 228 lebrikizumab subjects (1.8%), which include reports 
of chest pain, periprosthetic fracture, hernial eventration, and panic attack (Guttman-Yassky, 
2020).
Phase 3 studies with lebrikizumab in AD are currently ongoing; therefore, it is too soon to tell if 
the efficacy profile observed in the Phase 2b study will be replicated in registrational programs. 
However, lebrikizumab’s efficacy and safety profile observed in the high dose arm in Phase 2b
are encouraging, and support the hypothesis that higher dosing with therapeutic agents targeting 
IL-13 may be able to provide improved disease outcomes for patients with AD.
CC-93538 will be the most recent anti-IL-13 mAb to be evaluated as a potential therapeutic
option for subjects moderate to severe AD. Although CC-93538 shares a similar MOA to 
tralokinumab, as it prevents IL-13 binding to both IL-13Rα1 and IL-13Rα2 (Tripp, 2017), further
research is needed to better understand the role of IL-13 Rα2 in atopic skin inflammation and 
fibrosis (Furue, 2020). As response rates in AD studies vary across the current biologic agents, 
clinical investigations with new therapies, like CC-93538, provide a unique opportunity to 
potentially optimize efficacy, by leveraging existing knowledge available from similar
compounds. 
Approved
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Approved
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Approved
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
27
Protocol CC-93538-AD-001 Final: 13 Jan 2021
Testing to exclude COVID-19 infection prior to enrollment and to inform decisions about subject 
care during the study should follow local standard practice and requirements.
1.3.2.
Rationale for the Study Design
This is a randomized double-blind, placebo controlled, 4 arm, parallel-group study to evaluate 
the efficacy and safety of 3 doses, as compared to placebo, of CC-93538 in subjects with 
moderate to severe AD who are candidates for systemic therapy (ie, not adequately controlled by 
a stable regimen [≥ 4 weeks] of topical corticosteroids or calcineurin inhibitors or not eligible for 
topical therapy due to side effects or safety risks). 
Although this will be the first placebo-controlled efficacy and safety study of CC-93538 in 
subjects with AD, the pathophysiology of IL-13 as a key cytokine involved in type 2 
inflammatory conditions well supported throughout the literature.  CC-93538 is a mAb which is
highly selective for human IL-13, and as such, has a potential therapeutic benefit in treating 
subjects with moderate to severe AD.  Furthermore, the positive data observed in with other IL-
13 mAb (tralokinumab and lebrikizumab) summarized in section Section 1.3.1, have 
demonstrated that targeting IL-13, is an effective, and well tolerated treatment option in subjects 
with moderate to severe AD, warranting further exploration of CC-93538 as alternative anti-IL-
13 treatment option in this disease state.  
In the Phase 1 clinical studies, single doses up to 10 mg/kg IV have shown CC-93538 to have 
acceptable safety and tolerability, and PK properties consistent with other IgG1 mAbs. The 
Phase 2 study (RPC02-201) in subjects with EoE, further demonstrated the safety and tolerability 
of CC-93538, and showed continued clinical, endoscopic, and histologic improvements in 
subjects treated with 360 mg SC for up to 68 weeks of treatment.  The risk/benefit profile of CC-
93538, as demonstrated in the Phase 2 EoE Study, RPC02-201, supports further development in 
additional type 2 inflammatory conditions, such as AD. 
The 16-week treatment duration was selected based on an assessment of the efficacy and safety 
results from similar Phase 2 and Phase 3 AD studies, evaluating mAb (eg, dupilumab, 
lebrikizumab, and tralokinumab) with similar MOA, and terminal elimination half-life (t½) to 
CC-93538.  These studies showed that 16 weeks is an appropriate treatment duration to achieve a 
clinical response, across an array of standard efficacy measures in subjects with moderate to 
severe AD.  In addition, the 16 week treatment duration, is further supported by the efficacy 
results obtained in the double-blind portion of Study RPC02-201 summarized in Section 1.2.2.4. 
This study also demonstrated efficacy at the Week 16 time point by a reduction in esophageal 
eosinophil count in subjects with EoE. In addition, the follow-up period of an additional 16 
weeks is based the mean terminal elimination half-life (t½) for CC-93538, which ranged from 
16.4 to 26.7 days, similar to other mAbs. 
The primary efficacy endpoint is the percentage change from baseline in EASI score at Week 16. 
The EASI is a validated and widely used clinical trial endpoint in AD. Thus, it allows 
contextualization with the full spectrum of approved and experimental drugs offering maximum 
opportunity for benchmarking and modeling of the relationships between PK, PD, safety, and 
efficacy. This study will use it on a continuous scale to maximize statistical efficiency, as well as 
categorical endpoint of at least a 75% improvement Eczema Area and Severity Index (EASI-75)
that will be assessed as a key secondary endpoint.
Approved
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Approved
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
29
Protocol CC-93538-AD-001 Final: 13 Jan 2021
Based on the external data observed with other anti-IL-13 mAbs, it is important to understand 
whether treatment with CC-93538 
 
 can optimize the potential for clinical improvement in subjects 
with AD.  
1.3.4.
Rationale for Choice of Comparator Compounds
The study design employs a comparison to placebo which is intended to minimize bias and to 
provide an accurate determination of efficacy and safety findings attributable to CC-93538
administration.  Placebo is an acceptable control commonly used in AD studies to allow an 
assessment of clinical improvement related to a therapeutic candidate.  The ongoing use of non-
medicated topical emollient, as well as the allowance for rescue for intolerable AD symptoms 
further described in Section 8.4 has been employed in the study to ensure that all subjects enrolled 
in the study, including those on the placebo arm have symptom management interventions 
available within the context of the study. 
1.3.5.
Rationale for Pharmacodynamics and Potential Predictive Biomarkers 
Epidermal barrier defects, dysregulation of innate immune responses, and altered type 2 immunity 
are implicated in the pathogenesis of AD, culminating in complex inflammatory responses 
involving multiple cell types, cytokines and chemokines.  Relevant biomarkers including but not 
limited to peripheral blood eosinophils, immunoglobulin E (IgE), lactate dehydrogenase, IL-13, 
interleukin 22 (IL-22), chemokine (C-C motif) ligand 17 (CCL17)/thymus- and activation-
regulated chemokine (TARC), and chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and 
activation-regulated chemokine (PARC) will be evaluated for potential diagnostic or prognostic 
importance.
Approved
4.0
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Approved
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
30
Protocol CC-93538-AD-001 Final: 13 Jan 2021
2.
STUDY OBJECTIVES AND ENDPOINTS
Table 1:
Study Objectives
Primary Objective

To evaluate the clinical efficacy of 3 dosage regimens of CC-93538 (
 mg once 
weekly [QW], 
 mg every other week [Q2W], and 
 mg Q2W), compared with 
placebo on the change in the core clinical outcome measure, Eczema Area and Severity 
Index (EASI), in subjects with moderate to severe atopic dermatitis (AD)
Secondary Objectives

To evaluate the effect of 3 CC-93538 dosage regimens, compared with placebo on 
additional clinical outcome measures and patient reported outcomes in subjects with 
moderate to severe AD

To evaluate the safety and tolerability, including characterization of the 
immunogenicity profile, of 3 dosage regimens of CC-93538, compared with placebo in 
subjects with moderate to severe AD

To assess the serum trough concentration of CC-93538 in subjects with moderate to 
severe AD
Exploratory Objectives

To characterize the population pharmacokinetics (PK) of CC-93538 and to evaluate the 
exposure-response and pharmacodynamic relationships between CC-93538 exposure 
and efficacy, safety, and biomarker measures

To explore the onset of action associated with core clinical outcome measures in 
subjects with moderate to severe AD

To assess improvements from baseline in patient-reported outcome measures relevant 
to subjects with moderate to severe AD

To explore the effect of 3 dosage regimens of CC-93538 on AD-related inflammatory 
biomarkers, including, but not limited to peripheral blood eosinophils, immunoglobulin 
E (IgE), lactate dehydrogenase, interleukin 13 (IL-13), interleukin-22 (IL-22), chemokine (C-C 
motif) ligand 17 (CCL17)/thymus- and activation-regulated chemokine (TARC), and 
chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine 
(PARC)

To assess the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
serologic status on subjects receiving CC-93538 and AD and to support health 
authority requests
Approved
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Approved
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
31
Protocol CC-93538-AD-001 Final: 13 Jan 2021
Table 2:
Study Endpoints
Endpoint
Name
Description
Timeframe
Primary
Change in Eczema 
Area and Severity 
Index (EASI%)
Percent change in EASI from 
Baseline at Week 16
Week 16
Key Secondary
Validated Investigator 
Global Assessment for 
Atopic Dermatitis
(vIGA-AD) 0 or 1
Proportion of subjects with an vIGA-
AD score of 0 (clear) or 1 (almost 
clear) and a reduction ≥ 2 points 
from Baseline at Week 16
Week 16
EASI-75
Proportion of subjects with at least a 
75% improvement from Baseline in 
Eczema Area and Severity Index
(EASI-75) at Week 16
Week 16
Secondary
Change in Pruritus 
Numerical Rating Scale 
(NRS)
Percent change from Baseline in 
Pruritus NRS at Week 16
Week 16
Pruritus NRS Response 
Threshold
Proportion of subjects with Pruritus 
NRS change of ≥ 4 points from 
Baseline at Week 16
Week 16
Onset of Change in 
Pruritus NRS
Time to achieve at least 4 points of 
improvement in the severity of 
pruritus NRS scale in the first 16 
weeks of treatment
All planned time 
points through 
Week 16 
EASI-90
Proportion of subjects with at least a 
90% improvement from Baseline in 
Eczema Area and Severity Index 
(EASI-90) at Week 16
Week 16
SCORing Atopic 
Dermatitis (SCORAD) 
Index
Mean change in SCORAD Scores 
from Baseline at Week 16
Week 16
AD Body Surface Area 
(BSA) involvement
Percent change in BSA involved 
with AD from baseline at Week 16
Week 16 
Safety and Tolerability
Safety and tolerability evaluated by 
the incidence, severity, and 
relationship to CC-93538 of adverse 
events (AEs), serious adverse events 
(SAEs), clinical laboratory 
abnormalities, as well as an 
evaluation of the presence of serum 
antibodies to CC-93538.
All planned time 
points through 
Final Follow Up 
Visit  
Pharmacokinetics (PK)
Serum trough concentration of CC-
93538
All planned time 
points through 
Final Follow Up 
Visit 
Approved
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
32
Protocol CC-93538-AD-001 Final: 13 Jan 2021
Table 2:
Study Endpoints (Continued)
Endpoint
Name
Description
Timeframe
Exploratory
Onset of Action for 
Key Efficacy 
Parameters 
Proportion of subjects with at least a 
50% improvement from Baseline in 
Eczema Area and Severity Index
(EASI-50) in the first 4 weeks of 
treatment 
All planned time 
points through 
Week 4
Proportion of subjects to achieve 
EASI-75 in the first 4 weeks of 
treatment 
All planned time 
points through 
Week 4
Proportion of subjects with an vIGA-
AD score of 0 (clear) or 1 (almost 
clear) in the first 4 weeks of 
treatment 
All planned time 
points through 
Week 4
vIGA-AD 0 or 1 and 
EASI-75
Proportion of subjects achieving 
both a vIGA-AD score of 0 (clear) or 
1 (almost clear) and an EASI-75 at 
Week 16
Week 16 
PROMIS® Sleep 
Disturbance Short 
Form 8a
Mean change in sleep disturbance 
total score from Baseline to Week 16
Week 16
Patient Oriented 
Eczema Measure 
(POEM) Score
Mean change in POEM scores from 
Baseline to Week 16
Week 16
Dermatology Quality of 
Life Index (DLQI) 
Score
Mean change in DLQI score from 
Baseline to Week 16
Week 16
Hospital Anxiety and 
Depression Scale 
(HADS)
Mean change in anxiety and 
depression total scores from Baseline 
to Week 16
Week 16
Population PK
CC-93538 population 
pharmacokinetic parameters and 
covariates 
All planned time 
points through 
Final Follow Up 
Visit
Exposure-responses 
and pharmacodynamics 
relationship
Exposure-response and 
pharmacodynamics relationships 
between CC-93538 exposure and 
efficacy, safety measures (eg, AEs, 
labs, etc) and biomarkers
All planned time 
points through 
Final Follow Up 
Visit 
Approved
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
33
Protocol CC-93538-AD-001 Final: 13 Jan 2021
Table 2:
Study Endpoints (Continued)
Endpoint
Name
Description
Timeframe
Exploratory 
(Continued)
Biomarkers
CC-93538 treatment response as a 
function of baseline and change from 
Baseline in whole blood, serum, and 
tissue biomarkers (eg, peripheral 
blood eosinophils, immunoglobulin 
E [IgE], etc)
Week 16
Biomarkers
Exploratory Measurements of severe 
acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2)
serology (anti-SARS-CoV-2 total or 
IgG), from serum samples 
Day 1 and Week 
16
Approved
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Approved
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Approved
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
36
Protocol CC-93538-AD-001 Final: 13 Jan 2021
the End of Treatment Visit (Week 24) and the Final Follow Up/End of Study Visit will be 
conducted 16 weeks after the End of Treatment Visit (Week 32).
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.
Approved
4.0
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Approved
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
37
Protocol CC-93538-AD-001 Final: 13 Jan 2021
4.
STUDY POPULATION
4.1.
Number of Subjects
Approximately 200 adult subjects (aged 18 to 75 years) with moderate to severe AD will be 
randomized worldwide.
4.2.
Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subject must be ≥ 18 years and ≤ 75 years of age and have a body weight of ≥ 40 kg 
(88.2 lb) at the time of signing the informed consent form (ICF).  Subjects in Japan must 
also be of legal age of consent (≥ 20 years of age) at the time of signing the ICF.
2. Subject has chronic AD as defined by Hanifin and Rajka (Appendix B) that has been 
present for ≥ 1 year prior to the baseline visit (Day 1).
3. Subject has moderate to severe, active, and symptomatic AD defined by meeting all of 
the following criteria on the day of the baseline visit (Day 1):
a.
Body Surface Area (BSA) ≥ 10%, and
b. EASI score ≥ 16, and
c.
vIGA-AD ≥ 3, and
d. Pruritus NRS severity score ≥4.
4. Subject must have a documented history of inadequate response to treatment with topical 
medications for at least 4 weeks, unless topical treatments are otherwise medically 
inadvisable (eg, because of important side effects, safety risks, and/or previous 
intolerance), or has required systemic therapy for control of disease.
Inadequate response is defined as either or both of: 
a.
failure to achieve and/or maintain a disease activity state comparable to IGA 0 [clear]
to 2 [mild], despite treatment with a daily regimen of TCS of medium to higher 
potency (± TCI as appropriate), applied for at least 4 weeks (28 days) or for the 
maximum duration recommended by the product prescribing information, whichever 
was shorter, OR
b. necessity of systemic therapy to control disease.
5. Subject must be willing to apply a stable dose of topical emollient (eg, over-the-counter 
moisturizer, non-medicated emollient, etc.) twice daily for ≥7 days prior to the Baseline 
visit and continue application throughout the study.  Refer to Section 8.3 for additional 
requirements related to application of topical emollient throughout the study. 
6. Subject must commit to avoid prolonged exposure to the sun and not to use tanning 
booths, sun lamps or other ultraviolet light sources during the study.
7. Subjects currently receiving concomitant medications for any reason other than AD, such 
as inhaled corticosteroids, leukotriene receptor antagonists (eg, montelukast), or mast cell 
stabilizers (eg, cromolyn sodium) for asthma, must be on a stable regimen, which is 
defined as not starting a new drug, changing, or stopping dosage within 7 days or 5 half-
lives (whichever is longer) prior to Day 1 and through the treatment duration of the study.
Approved
4.0
v
Approved
1.0
v


EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
38
Protocol CC-93538-AD-001 Final: 13 Jan 2021
8. Female subjects of childbearing potential must agree to practice a highly effective 
method of contraception. Highly effective methods of contraception are those that alone 
or in combination result in a failure rate of a Pearl index of less than 1% per year when 
used consistently and correctly. A female of childbearing potential (FCBP) is a female 
who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or 
bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea 
following cancer therapy does not rule out childbearing potential) for at least 24 
consecutive months (ie, has had menses at any time in the preceding 24 consecutive 
months) and must:
a.
Have two negative pregnancy tests as verified by the Investigator prior to starting 
study therapy. She must agree to ongoing pregnancy testing during the course of the 
study and through the Final Follow-up Visit. This applies even if the subject practices 
true abstinence* from heterosexual contact.
b. Either commit to true abstinence* from heterosexual contact (which must be 
reviewed on a monthly basis and source documented) or agree to use, and be able to 
comply with, highly effective contraception without interruption throughout the study 
and for 5 months after the last dose of IP. 
Acceptable methods of birth control in this study are the following:
a.
combined hormonal (estrogen and progestogen containing) contraception, which may 
be oral, intravaginal, or transdermal
Note: Intravaginal and transdermal combined hormonal contraception are not 
approved by Japan Health Authority and would therefore not be acceptable methods 
contraception for subjects enrolled in this region.
b. progestogen-only hormonal contraception associated with inhibition of ovulation, 
which may be oral, injectable, or implantable.
Note: progestogen-only hormonal contraception is not approved by Japan Health 
Authority and would therefore not be acceptable methods contraception for subjects 
enrolled in this region.
c.
placement of an intrauterine device (IUD)
d. placement of an intrauterine hormone-releasing system (IUS)
e.
bilateral tubal occlusion
f.
vasectomized partner
g. sexual abstinence.
9. Subject is willing to receive weekly SC injections throughout the study.
10. Subject must understand and voluntarily sign an ICF prior to any study-related 
assessments/procedures being conducted.
11. Subject is willing and able to adhere to the study visit schedule and other protocol 
requirements.
                                               
* True abstinence is acceptable when this is the preferred and usual lifestyle of the subject.  Periodic abstinence (eg, 
calendar, ovulation, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), and lactational 
amenorrhea method are not acceptable methods of contraception.
Approved
4.0
v
Approved
1.0
v


EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
39
Protocol CC-93538-AD-001 Final: 13 Jan 2021
4.3.
Exclusion Criteria
1. The presence of any of the following will exclude a subject from enrollment: Evidence of 
an active and/or concurrent inflammatory skin condition (eg, seborrheic dermatitis, 
psoriasis, acute allergic contact dermatitis, etc.) that would interfere with the Investigator
or subject-driven evaluations of AD.
2. Evidence of acute AD flare between the Screening and Baseline/ Randomization (eg, 
doubling of the EASI score between Screening and Baseline).
3. Use of topical treatments that could affect the assessment of AD (eg, corticosteroids, 
calcineurin inhibitors, tars, antibiotic creams, topical antihistamines) within 7 days of the 
Day 1 visit.
4. Received phototherapy narrowband UVB (NB-UVB) or broad band phototherapy within 
4 weeks prior to the Baseline visit.
5. Evidence of immunosuppression, subject is receiving, or has received systemic 
immunosuppressive or immunomodulating drugs (eg, azathioprine, cyclosporine, 
systemic corticosteroids, interferon gamma (IFN-γ), Janus kinase inhibitors, 
methotrexate, mycophenolate-mofetil, etc.) within 4 weeks prior to the Baseline visit.
6.
Treatment with immunomodulatory biologics as follows:
a.
Dupilumab within 3 months of Baseline visit.
b. Cell-depleting biologics, including to rituximab, within 6 months prior to the Baseline 
visit.
c.
Other immunomodulatory biologics within 5 half-lives (if known) or 16 weeks prior 
to Baseline visit, whichever is longer.
7. Concurrent treatment with another IP, including through participation in an interventional 
trial for COVID-19. Prospective subjects may not participate in a concurrent IP study or 
have received an IP within 5 drug half-lives prior to signing the ICF for this study. 
Further, for subjects who received an investigational COVID-19 vaccine as part of a 
clinical trial prior to the first Screening Visit, enrollment must be delayed until the 
biologic impact of the vaccine is stabilized, as determined by discussion between the
Investigator and the Clinical Trial Physician.
8. Received a live attenuated vaccine within 1 month prior to the first Screening Visit or 
anticipates the need to be vaccinated with a live attenuated vaccine during the study. 
Administration of any live attenuated vaccine will be prohibited during the study through 
the Final Follow-up Visit.
9. Previously received CC-93538 treatment (formerly known as RPC4046 and ABT-308).
10. Liver function impairment or persisting elevations of aspartate aminotransferase (AST/
serum glutamic oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT/
serum glutamic pyruvic transaminase [SGPT]) that are 2 or more times the upper limit of 
normal (ULN), or total bilirubin 1.5 times the ULN. Subjects with elevations that are not 
clinically significant in total bilirubin associated with Gilbert's syndrome may participate.
Approved
4.0
v
Approved
1.0
v


EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
40
Protocol CC-93538-AD-001 Final: 13 Jan 2021
11. Active chronic or acute skin infection that requires treatment with systemic antibiotics, 
antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks prior to Day 1, or 
superficial skin infections within 1 week prior to Day 1.
12. Active parasitic/helminthic infection or a suspected parasitic/helminthic infection. 
Subjects with suspected infections may participate if clinical and/or laboratory 
assessments rule out active infection prior to randomization.
13. Ongoing infection (including but not limited to, hepatitis B or C, human 
immunodeficiency virus [HIV], or tuberculosis as defined by standard medical guidelines 
and as outlined in Section 6.1 for which testing to rule out is required during screening).
14. A previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection 
within 4 weeks prior to screening. Symptoms must have completely resolved and based 
on Investigator assessment in consultation with the Clinical Trial Physician, there are no 
sequelae that would place the participant at a higher risk of receiving investigational 
treatment.  Refer to Section 6.1.3 for additional guidance related to SARS-CoV-2 testing 
during screening.
15. Is pregnant or lactating.
16. A history of idiopathic anaphylaxis or a major immunologic reaction (such as 
anaphylactic reaction, anaphylactoid reaction, or serum sickness) to an immunoglobulin 
G (IgG) containing agent.  A known hypersensitivity to any ingredient in the 
investigational product (IP) is also exclusionary.
17. History of cancer or lymphoproliferative disease, other than a successfully treated non-
metastatic cutaneous squamous cell or basal cell carcinoma or adequately treated cervical 
carcinoma in situ, within 5 years of screening.
18. History of alcohol or drug abuse within 5 years prior to initiation of screening.
19. Any significant medical condition, laboratory abnormality, or psychiatric illness that 
would prevent the subject from participating in the study.
20. Any condition including the presence of laboratory abnormalities, which places the 
subject at unacceptable risk if he/she were to participate in the study.
21. Any other condition that confounds the ability to interpret data from the study.
Approved
4.0
v
Approved
1.0
v


EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
41
Protocol CC-93538-AD-001 Final: 13 Jan 2021
5.
TABLE OF EVENTS
Table 3:
Screening Visit Procedures
List of Screening Visit 
Study Procedures
Visit Timing
(Day -28 to Day 0)
Additional Notes (if applicable)
Informed consent (ICF)
X
Includes consent for the optional skin biopsy 
procedures.
Inclusion/Exclusion 
criteria
X
To be assessed at initially during screening and 
confirmed at Day 1.  
Screening laboratory tests will be used to determine 
eligibility for randomization with the exception of 
pregnancy tests, which will need to be confirmed by 
the Day 1 test results. 
The baseline validated Investigator Global 
Assessment for Atopic Dermatitis (vIGA-AD), 
Eczema Area and Severity Index (EASI), Body 
Surface Area (BSA), and the patient reported Pruritus 
Number Rating Scale (NRS) performed on Day 1 will 
be used to assess subject eligibility; the stratification 
data point for vIGA-AD score will be provided for 
randomization.
Demographics/baseline 
characteristics
X
Baseline characteristics and prior therapy assessments 
include the collection of details specifically related to 
atopic dermatitis (AD), including disease diagnosis 
and duration, the use of topical treatments, systemic 
treatments and other treatments for AD.
Medical history
X
Prior therapy
X
Concomitant therapy
X
All additional treatments (including prescription and 
over the counter [OTC] medications, herbal and 
dietary supplements, dietary modifications, and 
procedures) used by subjects within the 4 weeks (28 
days) prior to the first Screening Visit or at any time 
during the study.  Refer to Section 8 for additional 
guidance.
During screening subjects should be instructed to 
apply a stable dose of topical emollient (over-the-
counter moisturizer) twice daily for ≥7 days prior to 
the Baseline visit.
Adverse Events 
(AEs)/Serious Adverse 
Events (SAEs)
X
All AEs/SAEs will be recorded by the Investigator 
from the time the subject signs informed consent.  
Refer to Section 10 for additional guidance on 
AE/SAE collection.
Hematology and 
chemistry
X
Refer to Section 6.1 and Section 6.1.1 for additional 
guidance on the collection of safety laboratory 
samples.
Coagulation panel 
X
Urinalysis 
X
Approved
4.0
v
Approved
1.0
v


EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
42
Protocol CC-93538-AD-001 Final: 13 Jan 2021
Table 3:
Screening Visit Procedures (Continued)
List of Screening Visit 
Study Procedures
Visit Timing
(Day -28 to Day 0)
Additional Notes (if applicable)
Testing for hepatitis B 
and C and Human 
immunodeficiency 
virus
X
Testing for hepatitis B virus (HBV), hepatitis C virus 
(HCV), and Human immunodeficiency virus (HIV) 
will be performed at screening only, and will be 
analysed by the central laboratory.  Refer to 
Section 6.1 for additional details.
Testing for tuberculosis 
(TB)
X
Testing for TB will be performed at screening only.  
Active TB must be ruled out according to local 
medical practices.  TB must be assessed with a TB 
skin test, QuantiFERON Gold test, or other interferon 
gamma release assay (IGRA) (eg, T-SPOT).  Refer to 
Section 6.1 for additional guidance.
Pregnancy test females 
of childbearing 
potential (FCBP) only
X
A serum pregnancy test will be required at screening
Follicle-Stimulating Hormone (FSH) lab test should be 
performed to confirm that the status for subjects who 
assumed to be of non-childbearing potential. In the 
event of a positive urine test, the subject is not to be 
dosed, and confirmation with a serum pregnancy test 
should be performed.
For FCBP subjects: Birth control must be effective by 
the time the FCBP subject is randomized into the 
study (eg, hormonal contraception should be initiated 
at least 28 days before randomization).  If necessary, 
the randomization/Day 1 Visit may be delayed up to a 
maximum of 28 days to achieve the minimum 
treatment duration.  If the Day 1 Visit is delayed, the 
Medical Monitor should be contacted to confirm if 
any screening assessments (eg, safety labs, etc.) need 
to be repeated prior to randomization
Physical exam 
(complete)
X
A complete physical examination includes an
evaluation of heart, lung, head and neck, abdomen, 
neurological assessment, and extremities.
Height and Weight
X
Vital Signs
X
Vital signs:  Heart rate, blood pressure (systolic and 
diastolic), respiratory rate, and temperature will be 
assessed.  Blood pressure and pulse will be assessed 
in a sitting position and once the subject is at rest.  An 
automated validated device may be used, if available.  
Electrocardiogram 
(ECG)
X
Single 12-lead ECG will be conducted only at the 
Screening Visit when the subject is at rest and may be 
repeated to confirm any abnormal findings.
Approved
4.0
v
Approved
1.0
v


EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
43
Protocol CC-93538-AD-001 Final: 13 Jan 2021
Table 3:
Screening Visit Procedures (Continued)
List of Screening Visit 
Study Procedures
Visit Timing
(Day -28 to Day 0)
Additional Notes (if applicable)
Validated Investigator 
Global Assessment for 
Atopic Dermatitis 
(vIGA-AD)
X
The vIGA-AD must be conducted before the EASI 
assessment.  
Further information on this assessment  is available in 
Section 6.4.1 and Appendix C
Eczema Area and 
Severity Index (EASI)
X
Further information on this assessment  is available in 
Section 6.4.2 and Appendix D
Body Surface Area % 
(BSA)
X
Further information on this assessment  is available in 
Section 6.4.3 and Appendix E
Pruritus Numeric 
Rating Scale (NRS)
X
The electronic patient-reported outcome (ePRO) 
instrument on a handheld device will be distributed to 
subjects at the Screening Visit.  After completion of a 
training module, the Pruritus NRS will be completed
by the subject daily for at least the last week (7 days) 
during the Screening Period (prior to Day 1). 
Approved
4.0
v
Approved
1.0
v


EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
44
Protocol CC-93538-AD-001 Final: 13 Jan 2021
Table 4:
Treatment Period Procedures
Study Procedure
Treatment Perioda
EOT
/ET
Visit Label (V)
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
V15
V16
V17
Visit Week (W)
Day (d)
(Visit Window in Days)
W0 
d1
±3d
W1
d8
±3d
W2
d15
±3d
W3
d22
±3d
W4 
d29
±3d
W5 
d36
±3d
W6 
d43
±3d
W7
d50
±3d
W8
d57
±3d
W9 
d64
±3d
W10
d71
±3d
W11
d78
±3d
W12 
d85
±3d
W13 
d92
±3d
W14 
d99
±3d
W15 
d106
±3d
W16 
d113
±3d
Inclusion/
Exclusion Criteria
X
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Concomitant therapy
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AEs/SAEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematology and chemistry 
(pre-dose)
X
X
X
-
X
-
X
-
X
-
X
-
X
-
X
-
X
Fasting Lipid Panel (pre-
dose)
X
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
X
Urinalysis (pre-dose)
X
-
-
-
X
-
-
-
X
-
-
-
X
-
-
-
X
SARS-CoV-2 Serologyb
X
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
X
Pregnancy test (FCBP only)c
X
-
-
-
X
-
-
-
X
-
-
-
X
-
-
-
X
Physical exam complete
X
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
X
Physical exam brief
-
-
-
-
X
-
-
-
X
-
-
-
X
-
-
-
-
Weight 
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
X
Vital signs
X
X
X
-
X
-
X
-
X
-
X
-
X
-
X
-
X
Serum antibodies CC-93538
pre-dosed
X
X
X
-
X
-
X
-
X
-
X
-
X
-
X
-
X
Serum CC-93538 PK sample 
(pre-dose)
X
X
X
-
X
-
X
-
X
-
X
-
X
-
X
-
X
Whole blood and serum 
biomarker samples (pre-dose)
X
X
X
-
X
-
X
-
X
-
X
-
X
-
X
-
X
Skin Biopsy (Optional)e
X
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
X
Pharmacogenetic sample f
X
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Approved
4.0
v
Approved
1.0
v


EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
45
Protocol CC-93538-AD-001 Final: 13 Jan 2021
Table 4:
Treatment Period Procedures (Continued)
Study Procedure
Treatment Perioda
EOT
/ET
Visit Label (V)
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
V15
V16
V17
Visit Week (W)
Day (d)
(Visit Window in Days)
W0 
d1
±3d
W1
d8
±3d
W2
d15
±3d
W3
d22
±3d
W4 
d29
±3d
W5 
d36
±3d
W6 
d43
±3d
W7
d50
±3d
W8
d57
±3d
W9 
d64
±3d
W10
d71
±3d
W11
d78
±3d
W12 
d85
±3d
W13 
d92
±3d
W14 
d99
±3d
W15 
d106
±3d
W16 
d113
±3d
validated Investigator Global 
Assessment of Atopic 
Dermatitis (vIGA-AD)g
X
-
X
-
X
-
-
-
X
-
-
-
X
-
-
-
X
Eczema Area and Severity 
Index (EASI)
X
-
X
-
X
-
-
-
X
-
-
-
X
-
-
-
X
Body Surface Area (BSA) 
X
-
X
-
X
-
-
-
X
-
-
-
X
-
-
-
X
SCORing Atopic Dermatitis 
(SCORAD)
X
-
X
-
X
-
-
-
X
-
-
-
X
-
-
-
X
Pruritus NRS h
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Promise Sleep Disturbance 
Short Form 8a
X
-
-
-
X
-
-
-
X
-
-
-
X
-
-
-
X
Patient Oriented Eczema 
Measure (POEM)
X
-
-
-
X
-
-
-
X
-
-
-
X
-
-
-
X
Dermatology Life Quality 
Index (DLQI)
X
-
-
-
X
-
-
-
X
-
-
-
X
-
-
-
X
Hospital Anxiety and 
Depression Scales (HADS)
X
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
X
Randomization via IRT
X
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
IP administration i, j, k
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
-
Abbreviations:  AD = atopic dermatitis; ADA = anti-drug antibody; AE = adverse event; d = day, EASI = Eczema Area and Severity Index; ePRO = electronic patient reported 
outcome; EOT = End of Treatment, ET = Early Termination, FCBP = female of child bearing potential, FU=Follow Up; IP = investigational product; IRT = Interactive Response 
Technology; NRS = numerical rating scale; POEM = Patient Oriented Eczema Measure; PK = pharmacokinetics; SAE = serious adverse event; SARS-CoV-2 = Severe Acute 
Respiratory Syndrome Coronavirus 2; SCORAD = SCORing Atopic Dermatitis; TB = tuberculosis; vIGA-AD = validated Investigator Global Assessment of Atopic Dermatitis, V
= visit; Wk = week
a During the treatment period Day 1 through Visit 16/Week 15: On study visit days, showering or bathing is permitted prior to attending the study visit, but subjects must not 
moisturize or apply emollient. Non-medicated emollient is allowed after the visit.
b Serum will be collected at Day 1(Baseline), at the EOT/ET Visit, as well as approximately 4 weeks after a documented or suspected SARS-CoV-2 infection, for possible 
measurements of anti-SARS-CoV-2 total or IgG per national and local requirements.
Approved
4.0
v
Approved
1.0
v


EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
46
Protocol CC-93538-AD-001 Final: 13 Jan 2021
c For females of childbearing potential (FCBP), Urine (or serum) pregnancy test at Day 1, and urine pregnancy tests every 4 weeks thereafter are required.  At each study visit, the 
Investigator will counsel FCBP subjects on pregnancy precautions for the duration of the study.
d Further analysis on samples that are positive for ADA may be performed, including assessment of neutralizing antibodies when warranted.
e An optional skin biopsy procedure will be performed to measure tissue biomarkers including target expression levels and inflammatory biomarkers in subjects who consented.
f The pharmacogenetic sample will be collected from subjects, provided that necessary governmental and local approvals have been obtained.  If needed, the pharmacogenetic 
sample can be collected at any subsequent timepoint during the study.
g The vIGA-AD must be conducted before the EASI assessment.
h Pruritus NRS will be collected daily in a subject ePRO during the screening period. Scores will be captured daily from Day 1 (Baseline) through Week 4, followed by subsequent 
administration only on study visit/study drug administration days.  Score recorded at Day 1(Baseline) (pre-dose) should be used to assess eligibility criteria.  The electronic 
patient-reported outcome handheld device should be returned at the EOT/ET Visit.
i Once weekly IP administration (CC-93538 or placebo: subcutaneous [SC] doses on Day 1 followed by SC doses weekly from Week 1 through Week 15 [ie, a total of 16 weekly 
SC doses inclusive of the Day 1 dose]). The first 3 weekly SC doses will be administered in the clinic. Subjects will remain in the clinic for at least 30 minutes following dosing 
for observation for the first 3 visits.
j Starting at Week 3, subjects may have the option to return to the clinic every other week for IP administration, and have their alternate week injections administered at home by a
visiting home health nurse.  Subjects who utilize the home health nurse option will be required to return to the site every 2 weeks at a minimum (eg, Week 4 [Visit 5/Day 29], 
Week 6 [Visit 7/Day 43], Week 8 [Visit 9/Day 57], Week 10 [Visit 11/Day 71], Week 12 [Visit 13/Day85], Week 14 [Visit 15/Day 99], and Week 16 [Visit 17/Day 113]) during 
the treatment phase of study for scheduled laboratory collections, and additional safety and efficacy assessments.  In addition, on the weeks that the IP is not administered in-
clinic, the subject will be contacted by site personnel (within 24 hours) to assess for any changes in concomitant medication use and assess for adverse events. 
k Subjects for whom home health nurse services are not available in their region, or who choose not to utilize the visit home health nurse service option, will be required return to 
the clinic weekly for their injections.
Approved
4.0
v
Approved
1.0
v


EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
47
Protocol CC-93538-AD-001 Final: 13 Jan 2021
Table 5:
Follow Up Period Procedures
Study Procedure
Follow-Up (FU) Period
Additional Notes (if applicable)
Visit Label
Initial 
Follow Up
Visit 18
(Week 24)
Final Follow 
Up/
End of 
Study (EOS)
Visit 19
(Week 32)
Visit Timing
(Visit Window)
End of 
Treatment 
(EOT) Visit
+8 Weeks
(±7 day)
EOT Visit 
Last Dose 
+16 Weeks
(±7 day)
All visits conducted during the Follow Up 
Period are onsite visits.
Concomitant therapy
X
X
Refer to Section 8 for additional guidance.
Adverse Events 
(AEs)/Serious Adverse 
Events (SAEs)
X
X
Refer to Section 10 for additional guidance on 
AE/SAE collection.
Hematology and chemistry 
X
X
Refer to Section 6.1 and Section 6.1.1 for 
additional guidance on the collection of safety 
laboratory samples.
Urinalysis 
X
X
Urine (or serum) pregnancy 
test (female of child-bearing 
potential only)
X
X
At each study visit, the Investigator will 
counsel female of child-bearing potential 
(FCBP) subjects on pregnancy precautions for 
the duration of the study
Physical exam (complete)
X
X
A complete physical examination includes an 
evaluation of heart, lung, head and neck, 
abdomen, neurological assessment, and 
extremities.
Vital signs
X
X
Vital signs: Heart rate, blood pressure (systolic 
and diastolic), respiratory rate, and temperature 
will be assessed at each visit.  Blood pressure 
and pulse will be assessed in a sitting position 
and once the subject is at rest.  An automated 
validated device may be used, if available.  
Serum antibodies CC-93538
X
X
Further analysis on samples that are positive 
for anti-drug-antibodies (ADA) may be 
performed, including assessment of 
neutralizing antibodies when warranted.
Serum CC-93538
pharmacokinetic (PK)
sample 
X
X
Whole blood and serum 
biomarker samples 
X
X
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Cendakimab (CC-93538)
Protocol CC-93538-AD-001
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Confidential and Proprietary 
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Protocol CC-93538-AD-001 Final: 13 Jan 2021
Table 5:
Follow Up Period Procedures (Continued)
Study Procedure
Follow-Up (FU) Period
Additional Notes (if applicable)
Visit Label
Initial 
Follow Up
Visit 18
(Week 24)
Final Follow 
Up/
End of 
Study (EOS)
Visit 19
(Week 32)
Visit Timing
(Visit Window)
EOT Visit
+8 Weeks
(±7 day)
EOT Visit 
Last Dose 
+16 Weeks
(±7 day)
All visits conducted during the Follow Up 
Period are onsite visits.
Skin Biopsy (Optional)
X
An optional skin biopsy procedure will be 
performed to measure tissue biomarkers 
including target expression levels and 
inflammatory biomarkers in subjects who 
consented
validated Investigator Global 
Assessment of Atopic 
Dermatitis (vIGA-AD)
X
X
The vIGA-AD must be conducted before the 
EASI assessment.  
Further information on this assessment  is 
available in Section 6.4.1 and Appendix C
Eczema Area and Severity 
Index (EASI)
X
X
Further information on this assessment  is 
available in Section 6.4.2 and Appendix D
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
49
Protocol CC-93538-AD-001 Final: 13 Jan 2021
6.
PROCEDURES
Assessments and procedures for the Screening Period (Table 3), Treatment Period (Table 4), and 
the Follow-up Period (Table 5) are included in Section 5 the Table of Events. Study assessments 
and procedures are also described in Section 6.  The day of administration of the first dose of IP 
is defined as Day 1 (Baseline/pre-dose).
It is recommended that the study visits are scheduled in the morning.  Whenever possible, the 
assessment order sequence, as outlined in the Table of Events Section 5, should remain constant 
and should be conducted at approximately the same time of day throughout the study.
Any questions regarding the protocol should be directed to the Celgene Medical Monitor or 
designee.
6.1.
Screening Period
Screening evaluations will be performed for all subjects to determine study eligibility.  These 
evaluations must be completed within 28 days (4 weeks) prior to receiving the first dose of IP 
unless noted otherwise below.  Waivers to the protocol will not be granted during the conduct of 
this study, under any circumstances.
Screening procedures, as specified in the Table of Events detailed in Section 5, Table 3, will be 
performed for all subjects to determine study eligibility.  All screening procedures must be 
completed within 4 weeks prior to receiving the first dose of IP.  
The electronic patient-reported outcome (ePRO) instrument on a handheld device will be 
distributed to subjects at the Screening Visit.  After completion of a training module, the Pruritus 
NRS will be completed by the subject daily for at least the last week (7 days) during the 
Screening Period (prior to Day 1); however, value to assess inclusion criteria will be assessed on 
Day 1 (Baseline/pre-dose). 
Safety laboratory analyses and all assessments will be performed.  Screening laboratory values 
must demonstrate subject eligibility; however, analytes may be repeated (and analysed by the 
central laboratory) within the screening window, if necessary.
Written, signed, and dated informed consent from the subject prior to the performance of any 
study related procedures must be obtained by the Principal Investigator or designee (refer to 
Section 12.3 for further details regarding obtaining subjects informed consent).  A copy of the 
signed informed consent must be given to the subject for his/her records.
The following evaluations will be performed at screening as specified in the Table of Events, 
after informed consent/assent has been obtained:

Assessment of inclusion/exclusion criteria

Demographics and baseline characteristics

Medical history including atopy status (documentation of AD history, other atopic 
conditions, and past pharmacotherapy for AD, and other atopic conditions) and as 
well as details of any prior therapy or procedures to treat AD or other atopic 
conditions.
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
50
Protocol CC-93538-AD-001 Final: 13 Jan 2021

Prior therapy and concomitant therapy (including all procedures occurring ≤ 28 days 
before screening).  

Adverse event assessment begins when the subject signs the informed consent/assent 
form.  Throughout the course of the study, every effort must be made to remain alert 
to possible AEs or serious AEs (SAEs).  Once subjects consent, AEs/SAEs will be 
recorded at each study visit.  Refer to Section 10 for definitions of AEs/SAEs, 
monitoring, and reporting

Hematology, chemistry, coagulation panel, and urinalysis (central laboratory).  The 
following safety laboratory tests will be performed to assess the safety profile of CC-
93538:

Hematology:  red blood cell (RBC) count, total and differential white blood cell 
(WBC) count (basophils, eosinophils, lymphocytes, monocytes, and neutrophils), 
platelet count, hemoglobin (hgb), hematocrit (hct), mean corpuscular volume 
(MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin 
concentration (MCHC)

Blood chemistry:  indices included at all required chemistry timepoints are 
sodium, potassium, chloride, calcium, magnesium, phosphate, blood urea 
nitrogen, glucose (random, at timepoints not requiring fasting), albumin, alkaline 
phosphatase, creatinine, creatine phosphokinase (CPK), ALT/SGPT, AST/SGOT, 
gamma glutamyltransferase (GGT), amylase, total bilirubin, direct bilirubin and C 
reactive protein (CRP); in addition, fasting lipid panel (total cholesterol, 
triglycerides, high-density lipoprotein, and low-density lipoprotein) and fasting 
glucose (instead of random glucose) will be performed only at Day 1 and Week 
16/EOT/ET.

Coagulation:  Prothrombin time (PT), activated partial thromboplastin time 
(aPTT), and international normalized ratio (INR)

Urinalysis:  leukocytes, specific gravity, bilirubin, blood, glucose, ketones, pH, 
protein, and urobilinogen

Testing for hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV (central 
laboratory) will be performed at screening only.

HBV:   Hepatitis B surface antigen (HBsAg) screening test and hepatitis B core 
antibody (HBcAb) test will be performed.  Subjects who test positive for HBsAg 
will be excluded from the study.  For subjects who test positive only for HBcAb, 
an HBV deoxyribonucleic acid (DNA) test must be performed.  If the HBV DNA 
test is positive, the subject will be excluded from the study.  If the HBV DNA test 
is negative (without antiviral therapy) and ALT and AST are ≤ ULN, the subject 
will be eligible for this study.

HCV:  HCV antibody (anti-HCV IgG) test will be performed.  Subjects testing 
positive for HCV antibody and have a positive confirmatory test (HCV 
ribonucleic acid [RNA]) will be excluded from the study.  Subjects with evidence 
of cleared HCV infection (eg, HCV antibody positive subjects who are negative 
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
51
Protocol CC-93538-AD-001 Final: 13 Jan 2021
for HCV RNA) and who have not received anti-HCV therapy for at least 12 
weeks will be eligible for participation.

HIV:  An HIV antibody test will be performed.  Subjects testing positive for HIV 
(enzyme-linked immunosorbent assay [ELISA] test result, confirmed by western 
blot) will be excluded from the study.

Testing for tuberculosis (TB) will be performed at screening only.  Active TB must 
be ruled out according to local medical practices.  TB must be assessed with a TB 
skin test, QuantiFERON Gold test, or other interferon gamma release assay (IGRA) 
(eg, T-SPOT).  Subjects with latent TB must have documentation of completed 
prophylactic treatment by local standard of care.  Subjects with an indeterminate test 
result using any IGRA test, must be discussed for eligibility on a case by case basis 
by the Sponsor’s Medical Monitor or designee.  Subjects with latent TB who were 
only partially treated or who are currently receiving prophylactic treatment will not be 
eligible for randomization.

Serum pregnancy test (only for FCBP).  A test for the β-subunit of serum human 
chorionic gonadotropin (β-hCG) must be performed at screening in females of 
childbearing potential.  Urine (or serum) β-hCG will be performed at Day 1 and at the 
timepoints outlined in the Table of Events (Table 4).  In the event of a positive urine 
test, the subject is not to be dosed, and confirmation with a serum pregnancy test 
should be performed.  At screening and at each subsequent study visit, the 
Investigator will counsel FCBP subjects on pregnancy precautions for the duration of 
the study.

Physical examination:  A complete physical examination (including evaluation of 
heart, lung, head and neck, abdomen, neurological assessment, and extremities) will 
be performed.

Height and weight.

Vital signs: Heart rate, blood pressure (systolic and diastolic), respiratory rate, and 
temperature will be assessed.  Blood pressure and pulse will be assessed in a sitting 
position and once the subject is at rest.  An automated validated device may be used, 
if available.  

Electrocardiogram (ECG):  Single 12-lead ECG will be conducted only at the 
Screening Visit when the subject is at rest and may be repeated to confirm any 
abnormal findings.

AD disease activity assessments: 

vIGA-AD 

EASI

BSA

Pruritus NRS
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
52
Protocol CC-93538-AD-001 Final: 13 Jan 2021
6.1.1.
Additional Information Regarding Safety Laboratory Assessments
Analysis of samples will be conducted by a central laboratory.  Details regarding collection of 
samples, shipment of samples, reporting of results, laboratory reference ranges, and alerting 
abnormal values will be supplied to the site before site initiation in a Study Laboratory Manual. 
The results of the analysis will be made available to each site by the central laboratory. 
Additional and repeat laboratory safety testing may be performed locally at the discretion of the 
Investigator.  As local laboratory data will not be collected in the electronic case report form 
(eCRF), if feasible, a sample should also be sent to the central laboratory.  In addition, when 
safety laboratory samples are being collected to further assess AEs, it is recommended that 
serum samples to assess ADA and PK also be collected and sent to the central laboratory, when 
feasible. Laboratory samples required to confirm study eligibility (eg, liver function test, 
serology panel, etc) are required to be performed by the central laboratory if a retest is required 
during Screening. Retesting of specific laboratory parameters to confirm eligibility is allowed 
once during screening. If upon retest the subject still does not meet eligibility criteria, the subject 
should be screen failed.
Investigators will be asked to comment on those abnormalities on the respective laboratory result 
page, including a notation of the clinical significance of each abnormal finding in the subject’s 
source documents. The laboratory reports/records will be filed with the subject’s source 
documents. Reporting of laboratory AEs is described in Section 10.3. 
6.1.2.
Screening Failures and Rescreening of Potential Subjects
A screen failure is defined as a subject who has given informed consent/assent and failed to meet 
the inclusion and/or exclusion criteria. Subjects who initially fail to meet the inclusion/exclusion 
criteria may be re-screened as per the assessment of the Investigator.  Subjects who are re-
screened will be required to be re-consented and have all required Screening Visit procedures 
performed.  Subjects may be re-screened only 1 additional time for the study without prior 
consultation with the Medical Monitor.  
6.1.3.
Rescreening of subjects who develop COVID-19 during the Screening Period
Molecular testing for asymptomatic COVID-19 infection is not required in this study.  However, 
where local requirements or institutional practice are more restrictive, asymptomatic COVID-19 
screening may be performed locally, to ensure compliance with current local guidance.  In 
addition, some subjects may develop suspected or confirmed symptomatic COVID-19 infection, 
or it is discovered that subjects have asymptomatic COVID-19 infection during the Screening 
Period.  In such cases, subjects may be considered eligible for the study after meeting all 
Inclusion/Exclusion Criteria related to active infection, and after meeting the following criteria: 

At least 10 days (20 days for severe/critical illness) have passed since symptoms first 
appeared or positive test result, and

At least 24 hours have passed since last fever without the use of fever-reducing 
medications, and

Symptoms (eg, cough and shortness of breath) have resolved, and
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
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Protocol CC-93538-AD-001 Final: 13 Jan 2021

In the opinion of the Investigator, there are no COVID-19 sequelae that may place the 
subject at a higher risk of receiving investigational treatment, and 

Negative follow-up molecular test for COVID-19 based on institutional, local and/or 
regional guidelines and/or requirements
6.2.
Treatment Period
On Day 1, prior to randomization in the, the baseline assessments (including laboratory 
assessments, and the optional skin biopsy), as shown in the Table of Events Section 5, Table 4,
will be completed prior to the administration of IP.  The Investigator will review all available 
information to confirm subject eligibility.

Screening laboratory tests will be used to determine eligibility for randomization with 
the exception of pregnancy tests, which will need to be confirmed by the Day 1 test 
results.

A urine (or serum) pregnancy test must be performed for all females of childbearing 
potential on Day 1 and the results reviewed prior to randomization.  A negative 
pregnancy test result must be obtained prior to randomization.  If the urine pregnancy 
test result is positive but this is believed to be a false positive, the site must perform a 
serum pregnancy test at the local laboratory to confirm pregnancy status.

Baseline laboratory tests will be performed on Day 1 for comparison with follow-up 
tests.  However, the results of these tests will not be available prior to randomization 
on Day 1.

The baseline vIGA-AD, EASI, BSA, and the subject reported Pruritus NRS 
performed on 1 Day will be used to assess subject eligibility; the stratification data 
point for vIGA-AD score will be provided for randomization.
After eligibility has been confirmed and baseline assessments have been completed, eligible 
subjects will be randomized to treatment on Day 1.  Subsequent visits, assessments and 
procedures will be performed as per the Table of Events Section 5.  

Assessment of inclusion/exclusion criteria to confirm eligibility (Day 1 only)

Concomitant therapy

Assessment of AEs/SAEs. In addition, starting at Day 1, device (ie, pre-filled 
syringe) failures or malfunctions should be captured, and device related AEs should 
also be collected. 

Hematology, chemistry, fasting lipid panel, and urinalysis

Urine (or serum) pregnancy test (only for FCBP)

Physical examination (A complete physical examination (including evaluation of 
heart, lung, head and neck, abdomen, neurological assessment, and extremities) or an 
abbreviated (interim/brief) physical examination (including areas with previously 
noted abnormalities and/or that are associated with any new complaints from the 
subject) will be performed according to the Table of Events Section 5, Table 4
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
54
Protocol CC-93538-AD-001 Final: 13 Jan 2021

Weight

Vital signs

Serum antibodies to CC-93538

Serum CC-93538 PK assessment

Whole blood and serum biomarkers assessment

SARS-CoV-2 serology assessment

Pharmacogenetic assessment, if applicable per government and local regulations, will 
be collected one time at Day 1 (note, the sample may be obtained at any subsequent
visit).

Optional Skin Biopsy 

AD disease activity and efficacy assessments: 

vIGA-AD

EASI

BSA

SCORing Atopic Dermatitis (SCORAD) Index

Pruritus NRS

PROMIS Sleep Disturbance SF

Patient Oriented Eczema Measure (POEM)

Dermatology Life Quality Index (DLQI)

Hospital Anxiety and Depression Scale (HADS)

IP administration
Refer to Section 6.5 for a detailed description of the efficacy assessments and outcome measures 
conducted throughout the study.
6.2.1.
End of Treatment or Early Termination
For subjects who complete treatment phase of the study (Week 16) or discontinue the study 
prematurely for any reason (ie, subjects that do not complete Week 16) an EOT/ET visit will be
conducted.  For subjects who discontinue the study prematurely, every attempt should be made 
to complete the assessments detailed in the ET Visit conducted as close as possible to the time of 
study discontinuation.  If study discontinuation occurs at the regularly scheduled visit, the ET 
Visit and all corresponding ET Visit procedures should be conducted. In addition, these subjects 
should return for the Follow-up Visits.  
The evaluations that will be performed at the EOT/ET Visit are specified in Table of Events in 
Section 5.
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
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Protocol CC-93538-AD-001 Final: 13 Jan 2021
6.3.
Follow-up Period 
6.3.1.
Safety Follow-up (Initial [Week 24] and Final [Week 32])
All subjects will be followed for 16 weeks after the EOT/ET visit for AE reporting, as well as 
SAEs made known to the Investigator at any time thereafter that are suspected of being related to 
IP, as described in Section 10.1. Subjects will return for an Initial (Week 24) and a Final (Week 
32) Follow-up Visit at 8 and 16 weeks, respectively after completion of the EOT/ET Visit.  For 
subjects who prematurely discontinue from the study, the 16 Week Follow Up Period should be 
based off of the date of last study visit conducted during the Treatment Phase of the study (eg,
the ET visit) and therefore, may be conducted earlier then Week 24 and Week 32. 
The evaluations that will be performed at the Follow Up Visits are specified in Table of Events
Section 5, Table 5.
6.4.
Efficacy Assessments
The following efficacy assessments are completed by the Investigator include the validated 
Investigator Global Assessment for Atopic Dermatitis, Eczema Area and Severity Index, , Body 
Surface Area (BSA) % , and the SCORing Atopic Dermatitis Index.Clinical efficacy evaluations 
of atopic dermatitis will be performed by an experienced and qualified medical professional,
with experience in the conduct of AD clinical trials.
All efficacy evaluators must receive and document protocol specific and applicable efficacy 
assessment scales training prior to performing the evaluations. To assure consistency and reduce 
variability, the same evaluator must assess all dermatological clinical evaluations for any 
individual subject throughout the study whenever possible; a back-up experienced, and qualified, 
protocol-trained evaluator will only be allowed on rare occurrences, when the designated 
evaluator is unable to perform the evaluation.  Every effort should be made to ensure that the 
same assessor conducts the assessments at all study visits for a given subject.
6.4.1.
Validated Investigator Global Assessment 
The vIGA-AD is a validated 5-point assessment intended to assess the global severities of key 
acute clinical signs of AD, including erythema, induration/papulation, oozing/crusting 
(lichenification excluded). (Simpson, 2020) The rating of cleared (0), almost cleared (1), mild 
(2), moderate (3) and severe (4), will be assessed at scheduled visit specified in Section 5.  The 
vIGA-AD must be conducted before the EASI assessment. The IGA is a static evaluation 
conducted without regard to the score obtained at a previous visit.  Further details on the vIGA-
AD assessment are reference in Appendix C.
6.4.2.
Eczema Area and Severity Index
The EASI is a composite scoring system assessed by the Investigator based on the proportion of 
each of the 4 body regions (head and neck, upper limbs, lower limbs, and trunk) affected with 
AD and the intensity of each of 4 main signs of AD (eg, erythema, induration/papulation, 
excoriation, and lichenification) and is based on a 4-point scale of 0 (none), 1 (mild), 2
(moderate), and 3 (severe).
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
Protocol CC-93538-AD-001
Celgene International II Sàrl
Confidential and Proprietary 
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Protocol CC-93538-AD-001 Final: 13 Jan 2021
Assessment of the 4 main clinical signs is performed separately for 4 body regions: head and 
neck, upper limbs, trunk (including axillae and groin) and lower limbs (including buttocks). The 
total EASI score ranges from 0 to 72, with higher scores indicative of more severe disease.
Further details on the EASI assessment are referenced in Appendix D.
6.4.3.
Body Surface Area 
Body Surface Area involvement will be calculated from the sum of the number of handprints of 
skin afflicted with atopic dermatitis in a body region. The number of handprints of skin afflicted 
with atopic dermatitis in a body region can be used to determine the extent (%) to which a body 
region is involved with AD. When measuring, the handprint unit refers to the size of each 
individual subject’s hand with fingers in a closed position.  BSA will be calculated by the 
Investigator or qualified designee using the 1% handprint rule, in which the area represented by 
the palm with all 5 digits adducted together is approximately 1% of the subject's BSA Further 
details related to the BSA assessment are referenced in Appendix E.
6.4.4.
SCORing Atopic Dermatitis Index
The SCORAD is a validated scoring index for atopic dermatitis, which combines extent (0 to 
100), severity (0 to 18), and subjective symptoms (0 to 20) based on pruritus and sleep loss, each 
scored (0 to 10). The subject will assess the subjective symptoms (itch and sleepless) part of the 
assessment.  Further details related to the SCORAD index are referenced in Appendix F
6.5.
Subject Reported Efficacy Assessments and Outcome Measures
Subject reported efficacy assessments and patient reported outcome measure relevant to AD 
include the following assessments:

Pruritus Numeric Rating Scale

PROMIS Sleep Disturbance Short Form 8a

Patient Oriented Eczema Measure 

Dermatology Quality of Life Index 

Hospital Anxiety and Depression Scale
6.5.1.
Pruritus Numeric Rating Scale 
Pruritus will be assessed by the subject using the Pruritus NRS, which was developed and 
validated as a single item, patient reported outcome (PRO) of itch severity. Clinical response is 
indicated by a ≥2 to 4-point change from baseline in Peak Pruritus NRS score (Yosipovitch, 
2019) The intensity of pruritus will be assessed based on last 24 hours using a validated 11-point
NRS, ranging from 0 (“no pruritus”) to 10 (“the worst pruritus imaginable”). The subject will 
complete an electronic diary recording the intensity of their pruritus on daily basis, through 
Week 4, and weekly (eg, on study visit/study drug administration days) thereafter through the 
Week 16 visit. 
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
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Celgene International II Sàrl
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Protocol CC-93538-AD-001 Final: 13 Jan 2021
6.5.2.
PROMIS Sleep Disturbance Short Form 
The PROMIS Sleep Disturbance Short Form 8a is an 8-question subject questionnaire, designed 
to capture the subject’s perceptions of sleep quality, sleep depth, and restoration associated with 
sleep over the past week. The questionnaire is scored by: [sum of items x 8) ÷ number items 
answered]. The higher the total score, the more severe the symptom. Total scores less than 24 
suggest no to slight sleep disturbance, 24 to 28 suggest mild disturbance, 29 to 38 moderate 
disturbance, and greater than 38 severe sleep disturbance
The subject will complete the questionnaire onsite at study visits. 
6.5.3.
Patient Oriented Eczema Measure 
The Patient Oriented Eczema Measure (POEM) is a validated tool used for monitoring atopic 
eczema severity.  It is a 7-item questionnaire completed by the subject to assess the severity of 
eczema over the last week. The 7 questions each carry equal weight, and the responses are 
scored from 0 to 4 for a total score range of scored 0 to 28: To date, 2 published studies have 
broadly concurred that the minimally important change (MIC) of the POEM is 3 points
(Howells, 2018).
The subject will complete the questionnaire onsite at study visits. 
6.5.4.
Dermatology Quality of Life Index 
The DLQI will be completed by the subject at study visits.  It is self-administered, easy-to-use, 
dermatology-specific quality of life (QOL) questionnaire that consists of 10 questions related to 
a subjects’ perception of the impact of skin diseases on different aspects of their QOL over the 
last week. Questions are scored from 0 to 3, giving a possible total score range from 0 (meaning 
no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life).
6.5.5.
Hospital Anxiety and Depression Scale (HADS) 
The HADS is questionnaire completed by the subject that assesses anxiety and depression in a 
non-psychiatric population. The HADS has 2 subscales (depression and anxiety), both with 7 
questions. Responses are based on the relative frequency of symptoms over the past week, using 
a four-point scale ranging from 0 (not at all) to 3 (very often indeed). The HADS is completed by 
the subject at study visits.
6.6.
Safety Assessments
The safety parameters outlined in Section 5 that will be assessed in this study are the similar to
those used in previously or currently conducted clinical studies of CC-93538.  Careful safety 
monitoring of clinical and laboratory findings by both the sponsor’s medical monitors and by the 
Investigators has been implemented in this protocol. As this will be the first clinical study to 
further explore the safety and efficacy profile of CC-93538 at higher cumulative exposures, 
additional risk minimization measures, such as the frequency of onsite visits, ongoing blinded 
safety reviews of the study data, oversight from an internal Safety Management Team (SMT), 
and oversight from an external independent Data Monitoring Committee (DMC), will be 
implemented throughout this Phase 2 study to ensure that the safety of the subjects is adequately 
Approved
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Approved
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EDMS Doc. Number: 25275066 - 25256042
Cendakimab (CC-93538)
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monitored.  An overview of the additional safety oversight measures for the study are 
summarized below.
6.6.1.
Onsite Visit Frequency 
All subjects will return to the site weekly for the first 3 weeks for routine safety monitoring, IP 
administration, and a 30-minute post IP administration observation period.  Subjects will either 
return to the clinic weekly throughout the 16-week treatment period, or starting at Week 3, 
subjects may have the option to return to the clinic every other week for IP administration, and 
have their alternate week injections administered at home by a visiting home health nurse.  
Subjects who utilize the home health nurse option will be required to return to the site every 2 
weeks at a minimum (eg, Week 4 [Visit 5/Day 29], Week 6 [Visit 7/Day 43], Week 8 [Visit 
9/Day 57, Week 10 [Visit 11/Day 71], Week 12 [Visit 13/Day 85, Week 14 [Visit 15/Day 99], 
and Week 16 [Visit 17/Day 113]) to ensure additional safety assessments, such as the collection
safety laboratory samples, and onsite assessments by Investigator and site personnel can be 
performed.  Subjects who utilize the home health services option for any visits will still be 
contacted by site personnel (within 24 hours) to assess for any changes in concomitant 
medication use, and assess for AEs, to ensure there is continuity in the safety oversight being 
performed by the Investigator and site personnel. 
6.6.2.
Blinded Safety Data Reviews
From the start of the study (defined as first subject randomized) blinded safety reviews will be 
conducted by the internal study team/blinded data review team members on an ongoing basis. In 
addition, safety data will also be assessed by the SMT on a regular basis, and specific members 
of the SMT may also participate in the ongoing study data review related activities.  The 
expected frequency of these planned reviews is outlined below:

A preliminary interim blinded safety review involving the internal study team and the 
SMT will also be conducted after the first 8 subjects have received at least 4 weeks of 
treatment with IP.  A similar review will be initiated after the first 8 Japanese subjects 
have received at least 4 weeks of treatment. The purpose of these preliminary interim 
reviews will be to review data in a blinded, aggregate fashion to assess for any 
potential clinically significant safety findings early in the study conduct.  

From the start of the study (as defined as first subject randomized) ongoing blinded 
safety reviews will be conducted by the internal study team/data review team 
members on approximately a monthly basis.  More frequent review may be conducted 
on an ad-hoc basis if needed.
6.6.3.
Internal Safety Management Team
In addition to ongoing safety monitoring conducted by Investigators and study personnel, 
cumulative and interval blinded AEs, adverse events of special interest (AESI), SAEs, 
discontinuations due to AEs, and abnormal laboratory findings will be reviewed internally by the 
Sponsor Safety Management Team (SMT). The SMT is comprised of lead representatives from 
multiple Sponsor functions engaged in the CC-93538 development program. The scope, conduct, 
processes, and accountabilities are specified by the Sponsor’s Standard Operating Procedure 
(SOP). 
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Subject or study level safety assessments, and any subsequent study conduct related 
recommendations and/or actions provided by the SMT will be made from blinded data only.  The 
DMC will be informed of relevant subject or study level decisions made by the SMT. 
6.6.4.
Data Monitoring Committee Safety Oversight
A DMC, that is independent of the study team, and SMT, has been established to provide an 
additional level of safety oversight.   The DMC will function in advisory capacity, making 
recommendations the to study team and SMT based on their independent assessment of the 
safety data.  Members of the internal study team/data review team or SMT may also consult with 
the DMC on an ad-hoc basis throughout the duration of the study to discuss relevant safety 
findings (eg, SAE, AESI, findings related to subject discontinuation, etc) that may arise during 
study the conduct of the study. Additional details related to DMC structure and oversight are 
available in Section 9.9.3.
6.7.
Anti-drug Antibody Assessments
Serum samples to assess blood levels of antibodies to CC-93538 will be obtained pre-dose at 
study visits during the Treatment Period, at the EOT/ET visit, and the Follow-up Visits at the 
timepoints outlined in the Table of Events Section 5. 
Details of the procedures to be followed for sample collection, processing, storage, shipment, 
and testing will be documented in a separate Study Laboratory Manual.
The development of serum antibodies to CC-93538 will be monitored to assess the impact of 
immunogenicity on safety, PK, and efficacy of CC-93538.  The impact of immunogenicity will 
be evaluated by considering the results of PK, pharmacodynamic, and immunogenicity data 
taken together.  Samples will be stored for additional analysis if necessary.
Further analysis on samples that are positive for ADA may be performed, including assessment 
of neutralizing antibodies when warranted.  Samples will be stored for up to 5 years after study 
completion.
6.8.
Subject Reported Outcomes 
Patient reported outcome measure that will be assessed during the study are summarized above 
in Section 6.5.
6.9.
Pharmacokinetics 
Serum samples to assess CC-93538 concentrations will be obtained pre-dose at study visits at 
study visits during the Treatment Period, at the EOT/ET visit, and at the Follow-up Visits at the 
timepoints outlined in the Table of Events in Section 5. 
Details of the procedures to be followed for sample collection, processing, storage, shipment, 
and testing will be documented in a separate Study Laboratory Manual.
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6.10.
Biomarkers, Pharmacodynamics, Pharmacogenomics 
6.10.1.
Whole Blood and Serum Biomarker Assessments
Blood samples will be obtained pre-dose at study visits during the treatment period, at the 
EOT/ET visit, and the Follow-up Visits at the timepoints outlined in the Table of Events 
(Section 5) to evaluate levels of various biomarkers in whole blood and serum, including but not 
limited to peripheral blood eosinophils, IgE, lactate dehydrogenase, IL-13, IL-22, CCL17 
(TARC), and CCL18 (PARC), and possible assessments of SARS-CoV-2 serologic status, at the 
timepoints define in the Table of Event (Table 4, Table 5).  Serum will be collected for 
measurements of SARS-CoV-2 serology (anti-SARS-CoV-2 total or IgG) per national and local 
regulations. Of note, serum will be collected for SARS-CoV-2 serology at Day 1 (baseline), 
EOT/ET Visit, as well as approximately 4 weeks after a documented or suspected SARS-CoV-2 
infection, if applicable.
A pharmacogenomics sample will be collected only at one timepoint and is scheduled at Day 1 
(see Section 5) for biomarker assessment including but not limited to IL-13 single nucleotide 
polymorphism (SNP) characterization.  The pharmacogenetic sample will be collected from 
subjects, provided that necessary governmental and local approvals have been obtained.  If 
needed, the pharmacogenetic sample can be collected at any subsequent timepoint during the 
study.
These samples will be shipped to a central laboratory for analysis.  Details of the procedures to 
be followed for sample collection, processing, storage, and shipment will be documented in a 
separate Study Laboratory Manual.
6.10.2.
Tissue Biomarker Assessments
Skin punch biopsies will be optional but will be critical to a full understanding of response to 
these therapies in AD patients. Looking to future studies, having as many skin samples as 
possible will also allow for greater understanding of which tissue measures may have viable 
blood/serum surrogates and what can only be assessed accurately from biopsies. Skin punch 
biopsies from the site of the same AD lesion will be taken at baseline, at the EOT/ET, and at the 
Final Follow Up Visit.  For comparison, a biopsy of adjacent nonlesional skin will be taken at 
baseline, in order to provide a reference point.  Samples will either be frozen, placed in formalin, 
or sent into an equivalent process as appropriate for the experimental end use of the material (eg, 
separate processing for RNA extraction). Details for the biopsy procedures will be provided in 
the Study Laboratory Manual.
6.11.
Additional and Optional Research
Additional and optional research as described below may be performed using left-over samples 
originally collected for another test required in this study or using samples collected specifically 
for biomarker testing. The research may involve genetic tests using DNA or RNA and may lead 
to the development of new diagnostic tests.
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6.11.1.
Additional Research
Additional research related to the study drug and/or disease may be performed. The results of 
this additional research could help to improve the diagnosis and/or the treatment of this disease 
in the future. 
6.11.2.
Optional Research
Optional research not related to the study drug or the subject’s disease may be performed. The 
subject’s decision to participate in this optional research will not impact their ability to 
participate in the main study.
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85], Week 14 [Visit 15/Day 99], and Week 16 [Visit 17/Day 113]) during the treatment phase of 
study for scheduled laboratory collections, and additional safety and efficacy assessments. In 
addition, on the weeks that the IP is not administered in-clinic, the subject will be contacted by 
site personnel (within 24 hours) to assess for any changes in concomitant medication use and 
assess for AEs. 
Subjects for whom home health care provider services are not available in their region, or who 
choose not to utilize the service, will be required return to the clinic weekly to receive all of their 
IP injections. 
The SC doses should be administered in 
, in the abdomen or other
appropriate alternate location including the thigh or back of the upper arm (rotating the injection 
site each time), avoiding any blood vessels, thickened or tender skin, scars, fibrous tissue, stretch 
marks, bruises, redness, nevi, or other skin imperfections.
7.2.1.
Administration by a Visiting Home Health Care Provider
Starting at Week 3, subjects may have the option to return to the clinic every other week for IP 
administration, and have their alternate week injections administered at home by a visiting home 
health nurse.  Subjects who utilize the home health nurse option will be required to return to the 
site every 2 weeks at a minimum (eg, Week 4 [Visit 5/Day 29]. Week 6 [Visit 7/Day 43], Week 
8 [Visit 9/Day 57], Week 10 [Visit 11/Day 71], Week 12 [Visit 13/Day 85], Week 14 [Visit 
15/Day 99], and Week 16 [Visit 17/Day 113]) during the treatment phase of study for scheduled 
laboratory assessments, and additional safety and efficacy assessments. The home health care 
providers will be trained and will be able to monitor for injection site reactions at the time of 
administration. Within 24 hours of the home health care provider visit, the subject will be 
contacted by the site personnel to assess for any changes in AEs and/or concomitant medications.
Subjects for whom home health nurse services are not available in their region, or who choose 
not to utilize the visit home health nurse service option, will be required return to the clinic 
weekly for their injections.
7.2.2.
Missed Dose(s)
If subjects are unable to take a dose on the usually scheduled day:

They may take the dose within ±3 days of the normal dosing day and then continue 
dosing on their regular day the next week 

If the dose cannot be taken within ±3 days of the normal dosing day, they should wait 
to take their next dose on their regular dosing day the following week 
Any missed doses will be captured within the study records. If 3 or more consecutive doses are 
missed, the subject will be required to permanently discontinue IP.
7.2.3.
Overdose 
An overdose is any dose of IP given to a subject or taken by a subject that exceeds the dose 
described in the protocol.  There is no information regarding overdose with CC-93538.  Any 
overdose, with or without associated AEs, must be promptly reported to the Medical Monitor. 
See Section 10.1. Any doses of IP administered more frequently than the minimum of 3 calendar 
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days in between dose administrations allowed by visit window, further described in 
Section 7.2.2, should be reported as an overdose.
7.2.4.
Dose Adjustments
There is no provision for dose adjustments in this study. Subjects who cannot tolerate their 
assigned dose of IP, as determined by the Investigator, will be permanently discontinued from 
IP.
7.2.5.
Guidelines for Temporary Interruption of Dosing
Dosing for subject should be interrupted (temporary discontinuation of IP) if any of the 
following events occur:

The subject experiences any AE, intercurrent medical condition, or major surgery that 
could present an unreasonable risk to the subject due to study treatment continuation, 
as determined by the Investigator.

The subject experiences a single or multiple severe laboratory abnormalities. 
Laboratory tests should be repeated for confirmation within 48 to 72 hours from when 
the abnormality was first observed, when pragmatically possible.

The subject experiences an infection requiring parenteral treatment with antibiotic, 
antifungal, antiviral, antiparasitic, or antiprotozoal medications.

For an infection requiring oral treatment with antibiotic, antifungal, antiviral, 
antiparasitic, or antiprotozoal medications for longer than 2 weeks, interruption of IP 
is not required; however, the Investigator should determine if an interruption of 
dosing is in the best interest of the subject.

For local infections and recurrent infections, the Investigator should determine the 
appropriate action related to the interruption of IP.  Depending on the severity of the 
infection, the Investigator should contact the Medical Monitor to determine if 
additional actions, such as discontinuation of IP would be in the best interest of the 
subject.

For subjects who develop suspected or confirmed symptomatic COVID-19 infection, 
or it is discovered that subjects have asymptomatic COVID-19 infection during the 
Treatment Period.  IP should be temporary interrupted until the following conditions 
are met: 
For symptomatic subjects:

At least 10 days (20 days for severe/critical illness) have passed since symptoms 
first appeared or positive test result, and

At least 24 hours have passed since last fever without the use of fever-reducing 
medications, and

Symptoms (eg, cough and shortness of breath) have resolved, and

In the opinion of the Investigator, there are no COVID-19 sequelae that may place 
the subject at a higher risk of receiving investigational treatment, and,
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
Experiences 2 separate occurrences of severe injection site reactions (ISR) that last 
longer than 24 hours.

A severe ISR is defined as an ISR that manifests with symptoms causing severe 
discomfort/pain; symptoms requiring medical/surgical attention/intervention; 
interference with activities of daily life (ADLs) including inability to perform 
daily social and functional activities (eg, absenteeism and/or bed rest); and/or 
when drug therapy is required

Becomes pregnant

Uses prohibited systemic immunosuppressive or immunomodulating drugs 

Uses systemic rescue therapy

Misses 3 or more consecutive doses
These subjects will be encouraged to remain in the study and complete all required study 
assessments (which the exception of dosing with IP) remaining in the treatment period and 
follow up period of the study.  In order to prevent missing data, the site staff will ensure attempts 
are made to reach subjects by phone or email that do not maintain contact with the Investigator.  
Any subject discontinuing the study prematurely will be asked to complete the ET Visit and the 
Initial and the Final Follow-up Visits.
Additional events that are considered sufficient reasons for discontinuing a subject from the IP
are summarized in Section 11.1.
7.3.
Method of Treatment Assignment
Subjects enrolled in the study will be centrally randomized on Day 1 after all screening and 
baseline assessments have been completed and the Investigator has verified that the subject is 
eligible per the inclusion (Section 4.2) and exclusion criteria (Section 4.3).
Subjects will be randomized (1:1:1:1) to receive either CC-93538 (
 mg QW, 
 mg Q2W, 
or 
 mg Q2W) or placebo for 16 weeks. Treatment assignment will be stratified by geographic 
region (Japan versus rest of world). Within the rest of world region only, randomization will 
also be stratified by disease severity based on the Day 1 baseline validated Investigator Global 
Assessment for Atopic Dermatitis (vIGA-AD) score (3 [moderate] or 4 [severe]).  
Randomization will occur on Day 1 (Baseline) through the use of Interactive Response 
Technology (IRT) system, also referred to as an Interactive Web Response System (IWRS) 
system.
Treatment groups are described in Section 7.2. The treatment each subject will receive will not
be disclosed to the Investigator, study center personnel, subject, Sponsor or their representatives.
The treatment codes will be held according to the IWRS. Further instructions will be provided in
a separate IWRS manual.
The study blind should be maintained for persons responsible for the ongoing conduct of the
study (after all subjects have completed the Week 16 assessments for endpoint analysis).  
Blinded persons may include but are not limited to: Clinical Research Physician (also referred to
as Clinical Trial Physician), Clinical Research Scientist, Clinical Trial Manager, Study
Statistician, Data Manager, Programmers, and Clinical Research Associates (CRAs). For details
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of IP used and intervals between visits will be kept during the study.  Drug accountability will be 
noted by the field monitor during site visits and at the completion of the study. The IP should be 
dispensed by the Investigator, or by a qualified individual under the Investigator’s supervision.  
An up-to-date treatment inventory/dispensing record must be maintained.
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8.
CONCOMITANT MEDICATIONS AND PROCEDURES
All treatments (including prescription and over the counter [OTC] medications, herbal and 
dietary supplements, dietary modifications, and procedures) used by subjects within the 4 weeks 
(28 days) prior to the first Screening Visit or at any time during the study are regarded as prior or 
concomitant treatments and must be documented on the appropriate section of the eCRF.  In 
addition, a history of previous treatments for AD will be documented.  
All concomitant treatments, including blood and blood products, used from 28 days prior to the 
first Screening Visit until the Final Safety Follow-up Visit, or Final Study Visit must be reported 
on the eCRF. 
8.1.
Permitted Concomitant Medications and Procedures
The following concomitant medications are permitted during the study:

Oral antihistamines are permitted; however, the dose and regimen should remain 
stable from at least 2 weeks prior to the Day 1 (Baseline) Week 16, EOT/ ET visit). 
Subjects should also refrain from dosing within 24 hours prior to a study visit.

Subjects may use inhaled corticosteroids, leukotriene receptor antagonists (eg, 
montelukast), or mast cell stabilizers (eg, cromolyn sodium) for indications other than 
AD, such as asthma, if on stable doses/regimens for at least 4 weeks prior to the first 
Screening Visit and regimens should remain stable throughout the treatment duration 
of the study. If one of these medications was recently discontinued, it must have been 
discontinued at least 4 weeks prior to the first Screening Visit.

Medically necessary dose adjustments (eg to treat unanticipated exacerbations, etc) 
will be permitted; however, changes should consistent with local treatment 
guidelines. In addition, the Medical Monitor should be consulted to discuss the 
potential impact of the medication changes.

Ophthalmic corticosteroids are allowed for subjects receiving a stable dose to treat 
allergic conjunctivitis.
Unless prohibited, subjects may be administered any other medications necessary for the 
treatment of concurrent medical conditions or AEs, as deemed necessary by the Investigator. 
Following Day 1, addition of concomitant medications or any change in the dosage should be 
limited to those considered medically necessary.
8.2.
Prohibited Concomitant Medications and Procedures
The introduction of medications or therapies for other medical conditions known to affect AD 
(eg, systemic corticosteroids, mycophenolate-mofetil, interferon gamma (IFN-y), Janus kinase 
inhibitors, biologic therapies, TCS (except when given for rescue therapy), TCI, cyclosporine, 
azathioprine, methotrexate, phototherapy, etc) are not permitted during the study. 
Additional details related to the concomitant medications and procedures that are prohibited 
throughout the duration of the study are initially identified in the exclusion criteria (Section 4.3)
are summarized below.
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
Topical treatments that could affect the assessment AD (eg, corticosteroids, 
calcineurin inhibitors, tars, antibiotic creams, topical antihistamines) within 7 days of 
the Day 1 visit, and throughout the duration of study.    

Treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or 
antifungals within 2 weeks prior to Day 1; however, during the study, use will be 
allowed to treat infection AEs.

Phototherapy narrowband UVB (NB-UVB) or broad band phototherapy within 4 
weeks prior to the baseline visit, and throughout the duration of the study. 

Systemic immunosuppressive or immunomodulating drugs (eg, azathioprine, 
cyclosporine, systemic corticosteroids, IFN-γ, Janus kinase inhibitors, methotrexate, 
mycophenolate-mofetil, etc.) within 4 weeks prior to the Baseline visit, and 
throughout the duration of the study.

Treatment with immunomodulatory biologics as follows, and throughout the duration 
of the study:

Dupilumab within 3 months of Baseline visit.

Cell-depleting biologics, including to rituximab, within 6 months prior to the 
Baseline visit.

Other immunomodulatory biologics within 5 half-lives (if known) or 16 weeks 
prior to Baseline visit, whichever is longer

With the exception of oral antihistamines, any additional medications and/or 
treatments that could affect AD are also prohibited throughout the study. 

Due to the potential to affect AD with ultraviolet light exposure, subjects must also 
avoid prolonged exposure to the sun and not to use tanning booths, sun lamps or other 
ultraviolet light sources during the study.

Concurrent treatment with another IP, including through participation in an 
interventional trial for COVID-19 are prohibited throughout the duration of the study. 
Prospective subjects may not participate in a concurrent IP study or have received an 
IP within 5 drug half-lives prior to signing the ICF/assent for this study. Further, for 
subjects who received an investigational COVID-19 vaccine as part of a clinical trial 
prior to the first Screening Visit, enrollment must be delayed until the biologic impact 
of the vaccine is stabilized, as determined by discussion between the Investigator and 
the Clinical Trial Physician.

Live attenuated vaccines are prohibited within one month prior to the first Screening 
Visit, and throughout the duration of the study.
8.3.
Required Concomitant Medications and Procedures
Non-medicated topical emollient should be applied twice daily for ≥7 days prior to the 
Baseline/Day 1 visit and application (at the same twice daily frequency) should continue 
throughout the study.  On study visit days, subjects must not moisturize or apply emollient 
before the visit.  The last application emollient should be applied the night before the planned 
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study visit.  Non-medicated emollient is allowed after the visit is completed, and the same type 
of emollient should be used throughout the duration of the study.
8.4.
Rescue Medication
In the event a subject develops intolerable AD symptoms that requires rescue therapy, exceptions 
related to prohibited medications, such as TCS use, will be permitted. The use of rescue therapy 
should be discouraged throughout the treatment phase of trial, and reserved for only severe 
symptoms associated with AD flares.  In such cases, subjects may continue study participation, 
while continuing concomitant rescue therapy use; however, discontinuation of IP may be 
required depending on the type of rescue medication that is administered.  

Subjects requiring rescue therapy should consider the addition of TCS prior to 
considering systemic treatment. Any subject who requires TCS rescue therapy 
treatment are encouraged to continue the TCS for as brief a period as possible (eg less 
than 7 days), while continuing with treatment with IP, and maintaining the study visit 
schedule.

Any subject requiring systemic rescue therapy to treat their AD during the treatment 
phase of the study will be discontinued from IP and will be encouraged to continue 
participation in the study without IP administration. Subjects who decline further 
participation in the study should proceed with the Early Termination Visit and follow 
up visit assessments.  Subjects requiring systemic rescue therapy during the follow up 
period of the study should continue the study visits as planned.  All instances of 
rescue therapy administration that occur during the course of study participation will
be captured accordingly within the source documentation in the eCRF.
The impact of rescue therapy will also be evaluated by defining these endpoints as missing for 
subjects who initiate rescue therapy prior to Week 16 and analyzed according to methods 
described in Section 9.
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9.
STATISTICAL CONSIDERATIONS
9.1.
Overview
This is a Phase 2, multicenter, global, randomized, double-blind, placebo-controlled, parallel-
group study to evaluate the safety and efficacy of CC-93538 in adult subjects with moderate to 
severe AD. Subjects will be randomized to receive study medication for 16 weeks and the 
randomization will be stratified by geographic region (Japan versus rest of world) and, within 
RoW region only, randomization will also be stratified by disease severity based on baseline 
vIGA-AD score (3 [moderate] or 4 [severe]). An independent DMC will be used to review the 
safety data regularly during the course of the study.
Analysis details not explained in the statistical section of the protocol will be provided in the 
Statistical Analysis Plan (SAP).  
9.2.
Study Population Definitions
The following analysis populations will be used in the statistical analysis:
Modified intent to treat (mITT) Population
All randomized participants who received at least 1 dose of IP.
The mITT population will be used as the primary population for all efficacy parameters.  
Subjects who prematurely withdraw from the trial for any reason and for whom an assessment is 
not performed for any reason will still be included in the mITT population.  Subjects will be 
included in the treatment group to which they are randomized.  Subjects who were randomized 
with a misreported stratum will be classified according to their original (misreported) stratum. 
Safety Population
The Safety population will consist of all subjects who received at least one dose of IP.  This 
population will be used for all summaries of safety data.  Subjects randomized to placebo who 
receive any dose of CC-93538 will be summarized in the CC-93538 group.  Subjects randomized 
to CC-93538 who receive only placebo will be summarized in the placebo group; otherwise, they 
will be summarized in the CC-93538 group.
Pharmacokinetic Population
All subjects who received at least one dose of active drug and have at least one measurable 
concentration data.
Biomarkers
All participants that received any study treatment and have any available biomarker 
measurement.
9.3.
Sample Size and Power Considerations
Approximately 200 subjects will be randomized in this Phase 2 dose ranging study. 
Randomization will be equal among the 4 dose groups of placebo, 
 mg Q2W, 
 mg Q2W, 
and 
 mg QW (approximately 50 subjects per group). 
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Assuming a 10% dropout rate, a sample size of 45 subjects per group will provide approximately 
90% power to detect a treatment difference relative to placebo (difference in means) of 35% with 
respect to the primary endpoint of percentage change from baseline in EASI scores at Week 16.  
In these power calculations superiority over placebo for a particular dose group is met if the 
lower bound of the (2-sided) 95% confidence interval (z-score) for the treatment difference 
exceeds zero (adjusted for multiplicity).
The sample size calculations are based on the following considerations for comparing mean 
percentage changes from baseline in EASI scores at Week 16 versus placebo. In particular, the
recent Phase 2b study of dupilumab reported an observed mean for placebo of 18.1% and 
corresponding treatment differences of 50.1% (standard error [SE = 6.7%]) and 55.7%                
(SE = 6.7%), for the doses of 300 mg Q2W, and 300 mg QW, respectively (Thaçi, 2016). This 
study evaluating CC-93538 is designed to detect a (true) treatment difference relative to placebo 
of 35%.  We assume a (true) mean of 20% for placebo, and means for the active dose groups 
corresponding to treatment differences of 25% 
 mg Q2W), 30% 
mg Q2W), and 35% 
(
 mg QW), with a common standard deviation (SD) of 50%. We note that the common SD 
assumption of 50% for the percentage change from baseline in EASI scores at Week 16 was also 
assumed in the dupilumab Phase 2b study design (Thaçi, 2016). Under these assumptions, it is
estimated that with a sample size of 45 subjects per group the study provides approximately 90% 
power to detect superiority relative to placebo for at least 1 dose at the overall type-1 error of α = 
0.05 (two-sided) using a hierarchical testing approach (in the order of 
mg QW versus 
placebo, 
mg Q2W versus placebo, and 
 mg Q2W versus placebo). 
In addition, the study will provide more than 90% power to detect superiority relative to placebo 
for at least one dose with respect to the key secondary endpoint of vIGA-AD response (0-clear, 
1-almost clear) at Week 16 assuming true proportions of 2% (placebo), 15% 
 mg Q2W), 
25% (
mg Q2W), and 25% 
 mg QW). We note that the Phase 2 dupilumab study 
reported proportions of 30% and 33% for the doses of 300 mg Q2W, and 300 mg QW, 
respectively (Thaçi, 2016).  The hierarchical testing approach used for the primary endpoint was 
utilized to maintain the overall type-1 error of α = 0.05 (two-sided) with respect to the IGA 
response endpoint.  However, multiplicity adjustments are not implemented across endpoints 
jointly (eg, for both the primary and key secondary endpoints simultaneously).
9.4.
Background and Demographic Characteristics
Summaries for the demographics, baseline characteristics, medical history, prior medications, 
and protocol deviations will be presented for the mITT population by treatment groups.  
Concomitant medications will be presented for the Safety population by treatment groups.  
Individual listings will also be provided, including concomitant medical procedures for the 
Safety population.
9.5.
Subject Disposition
The disposition of subjects will be summarized with numbers and percentages by treatment 
group for all enrolled subjects.  Summaries will include the number and percentage of subjects in 
the following categories:
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
Randomized, dosed (at least one dose of study treatment), permanently discontinued 
from IP, discontinued from the study, discontinued from IP and remained in study 
follow up, and completed study

Primary reasons for discontinuation from the study
9.6.
Efficacy Analysis
9.6.1.
Efficacy Analysis of the Primary Endpoint
9.6.1.1.
Percentage Change from Baseline in EASI Scores at Week 16
The primary efficacy endpoint of percentage change from baseline in EASI scores at Week 16 
will be analyzed using an analysis of covariance (ANCOVA) model, based on the modified 
intent to treat (mITT) population, with treatment group indicators as the main effects adjusting 
for baseline EASI scores, and the stratification factors of vIGA-AD score (3 [moderate] or 4 
[severe]) and region (Japan versus RoW) as covariates. For each of the active treatment arms, 
the adjusted mean percentage changes from baseline and corresponding differences versus 
placebo in EASI scores at Week 16 will be estimated (based on Least-Squares Means) along 
with 95% Wald confidence intervals (CIs) and p-values.
Missing EASI scores at Week 16 (eg, due to study dropout or other reasons for lack of 
assessment) will be handled using a multiple imputation (MI) approach (SAS Institute, 2015)
under a missing at random (MAR) assumption.  In the sequel we refer to this as the MI approach.
To adjust for multiplicity, a standard hierarchical approach will be utilized by conducting 
comparisons, each at the 2-sided 0.05 alpha-level (based on the aforementioned adjusted p-
values), in the order of 
mg QW versus placebo,
 mg Q2W versus placebo, and 
mg 
Q2W versus placebo.
Sensitivity analyses will be conducted to support the primary analysis by utilizing an alternative 
missing data approach as well as by assessing the impact of rescue therapy. The first sensitivity 
analysis will replace the MI approach for missing EASI scores at Week 16 with imputation by 
LOCF (last observation carried forward). The second and third sensitivity analyses will evaluate 
the impact of rescue therapy by defining EASI scores after rescue therapy (prior to Week 16) 
initiation as missing.  The second sensitivity analysis will apply the MI approach with the 
addition (further degree) of missingness due to rescue.  The third sensitivity analysis will 
combine the first and second sensitivity analyses by replacing the MI approach in the second 
sensitivity analysis with LOCF.
9.6.1.2.
Subgroup Analysis of Primary Endpoint
To assess whether the treatment effect is consistent across various groups, subgroup analyses 
will be performed for the primary endpoint at Week 16.  Treatment differences and 2-sided 95% 
CIs will be provided for each subgroup listed below.  Forest plots for the treatment differences
by subgroup will also be provided. 
1. Non-elderly adults [< 65 years] versus elderly adults [ ≥ 65 years])
2. vIGA-AD baseline score (4 versus 3)
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3. Sex (female versus male)
4. Region (Japan versus Rest of world) 
5. Race (white versus non-white)
6. Prior experience with systemic immunosuppressive drugs
If there are not enough subjects (eg, < 8% mITT population, based on observed cases) in each 
subgroup and treatment category, the corresponding subgroup analyses will not be performed; 
instead, summary statistics will be provided. Details will be described in the SAP
Additional planned subgroup analyses may be considered and further defined in the SAP.
9.6.2.
Efficacy Analysis of Secondary Endpoints
9.6.2.1.
Analysis Methods
For the first key secondary endpoint of proportion of subjects with both a vIGA-AD score of 0 
(clear) or 1 (almost clear) and a reduction of 2 or more points in vIGA-AD score from Baseline 
at Week 16 will be analyzed based on the mITT population using a stratified 
Cochran-Mantel-CMH test at a two-sided 5% significance level.  The randomization 
stratification levels are: (1) Japan region, (2) RoW region and vIGA-AD score 3, and (3) RoW 
region and vIGA-AD score 4. Estimates of the differences in proportions between each treatment 
group versus placebo, and associated 95% confidence intervals will be provided along with p-
values. Missing endpoint values (eg, due to study dropout or other reasons for lack of 
assessment) will be imputed as non-responders.  A sensitivity analysis will be conducted based 
on defining subjects who initiate rescue therapy (prior to Week 16) as missing and treated as 
non-responders. 
The second key secondary endpoint of proportion of subjects with at least a 75% improvement 
from baseline in Eczema Area and Severity Index (EASI-75) at Week 16 will be analyzed in the 
same manner as above.
The hierarchical testing approach used for the primary endpoint will be utilized to adjust for 
multiplicity with respect to the 3 active doses for each of these key secondary endpoints.  
However, multiplicity adjustments are not implemented across the primary and 2 key secondary 
endpoints simultaneously.
The following endpoints will be analyzed in the same manner as the key secondary endpoints, 
excepting that p-values will not be provided:

The secondary endpoint of proportion of subjects with Pruritus NRS change of ≥ 4 from 
Baseline at Week 16

The secondary endpoint of proportion of subjects with a 90% improvement from Baseline 
in EASI (EASI-90) at Week 16
The following endpoints will be analyzed in the same manner as the primary endpoint, excepting 
that p-values will not be provided:

The secondary endpoint of percentage change from baseline in Pruritus NRS at Week 16 

The secondary endpoint of percent change in SCORAD Scores from Baseline at Week 16 
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
The secondary endpoint of mean percent change in Body Surface Area (BSA) involved 
with AD from Baseline at Week 16 
For the secondary endpoint of time to achieve at least 4 points of improvement in the severity of 
pruritus NRS scale in the first 16 weeks of treatment, the distribution of times to the first event of 
4-point improvement will be compared based on Kaplan-Meier (K-M) and log-rank approaches.  
Comparisons versus placebo, for each dose group separately, will be based on a stratified log-
rank test with associated p-value provided. The stratification levels are: (1) Japan region, (2) 
RoW region and IGA score 3, and (3) RoW region and vIGA-AD score 4. The K-M estimates 
for the cumulative proportions of subjects achieving a 4-point improvement, by specific 
timepoints, will be provided by dose group as well as differences with placebo and associated 
95% confidence intervals. These will be reported at various timepoints (eg, Day 1 to 28, 
followed by weekly assessments). Censoring rules will be described in the SAP.
9.7.
Safety Analysis
All analyses of safety data will be conducted using the Safety population by treatment for the 
entire study duration of 32 weeks.  The assessment of safety will include AEs, SAEs, AEs 
leading to discontinuation of study treatment, and AEs leading to discontinuation from the study;
changes from baseline in laboratory values and vital signs; and incidence and type of laboratory, 
vital signs, and physical examination abnormalities.  Individual data listings will also be 
provided.
Adverse events will be monitored during the trial, and the data will be summarized by worst 
severity grade. Adverse events, with focus on treatment-emergent AEs, will be summarized by 
Medical Dictionary for Regulatory Activities (MedDRA) system organ class, and preferred term.  
Investigational product-related AEs, AEs leading to death or to discontinuation from treatment, 
events assessed as moderate or severe, IP-related events, and SAEs, and events of interest.
Laboratory assessments will be performed by a central laboratory.  All summaries will be based 
on the Standard International System of Units (SI) provided by the central lab.  Each subject’s 
hematology, blood chemistry, and urinalysis values will be flagged as “low”, “normal”, or 
“high” relative to the normal ranges of the central laboratory. 
Summary statistics of actual values and changes from baseline in vital signs will be provided by 
visit.
9.8.
Interim Analysis
No formal interim analysis is planned for this study.
9.9.
Other Topics
9.9.1.
Analysis of Exploratory Endpoints
Exploratory analyses will be conducted on the exploratory efficacy endpoints listed in Section 2. 
Exploratory efficacy endpoints will be summarized using descriptive statistics by treatment 
group.  For continuous endpoints, number of subjects (n), mean, SD, SE, median, minimum, and 
maximum will be provided.  Binary endpoints will be summarized by number and percentages.  
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9.9.2.
Pharmacokinetics, Pharmacodynamics and Exposure-Response
Serum trough concentrations (Ctrough) of CC-93538 will be summarized with descriptive statistics 
by treatment and visit.  Additional analysis may be conducted as appropriate (eg, by ADA 
status).
Population PK analysis will be performed using nonlinear mixed-effects modeling to 
characterize the population PK of CC-93538 and to identify key covariate effects (eg, 
immunogenicity, intrinsic and extrinsic factors).  Data from other studies may be included if 
appropriate.  Exposure-response and pharmacodynamic relationships will be conducted for 
efficacy, safety, and biomarker endpoints.  Details on the studies and methodology will be 
outlined in a separate PK Analysis Plan, and results will be issued separately from the clinical 
study report as a stand-alone report.
9.9.3.
Data Monitoring Committee
Additional safety monitoring will be performed by an external, independent Data Monitoring 
Committee (DMC). A DMC will be convened that will include physicians with experience in 
treating subjects with type 2 inflammatory diseases, as well as a statistician, all of whom are not 
otherwise involved in the study conduct and for whom there is no identified conflict of interest.
During the study, the DMC will review selected data (to be specified in the DMC charter) on a 
regular basis for the assessment of benefit-risk and determination of study continuation. An 
independent third party will prepare the reports of aggregate data summaries and individual 
subject data listings, as appropriate, for the DMC members for each scheduled meeting. 
Operational details for the DMC, including a blinding plan to assure that all personnel involved 
in the conduct of the study remain blinded to the results of data reviews, will also be described in 
the DMC charter.  The DMC will function in advisory capacity, making recommendations based 
on their independent assessment of the safety data.  Unblinded safety data may be reviewed on a 
periodic or ad-hoc basis by the DMC, as needed, to further enhance the ongoing assessment of 
the risk/benefit of the IP.  
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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 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 7.2.3 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. 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 CC-93538 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 16 weeks after the last dose of IP, or the last Follow Up visit, whichever is longer, as well 
as those SAEs made known to the Investigator at any time thereafter that are suspected of being 
related to IP.  All AEs (serious/non-serious) will be recorded on the CRF and in the subject’s 
source documents.  Refer to Section 10.5 for instructions on how to report SAEs to Drug Safety. 
10.2.
Evaluation of Adverse Events
A qualified Investigator will evaluate all adverse events as to: 
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);
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
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 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.
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. 
The following grading scale should be used to evaluate severity/intensity:
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
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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.
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 IP
that has not been manufactured or provided by Celgene, 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. 
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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.
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 either a female subject of childbearing 
potential or partner of childbearing potential of a male subject are immediately reportable events.  
10.4.1.
Females of Childbearing Potential
Pregnancies and suspected pregnancies (including elevated β-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 5 months of the subject’s last dose of IP are considered immediately reportable 
events.  Investigational product is to be discontinued immediately. The pregnancy, suspected 
pregnancy, or positive pregnancy test must be reported to Celgene Drug Safety immediately by 
email, phone or facsimile, or other appropriate method, using the Pregnancy Initial Report Form, 
or approved equivalent form.  
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 Celgene Drug Safety immediately about the outcome of the pregnancy (either normal or 
abnormal outcome) using the Pregnancy Follow-up Report Form or approved equivalent form.
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11.
DISCONTINUATIONS
11.1.
Treatment Discontinuation
The following events are considered sufficient reasons for permanently discontinuing a subject 
from the IP:

Adverse event 

Physician decision

Lack of efficacy

Protocol deviation

Withdrawal by subject 

Death

Lost to follow-up

Non-compliance with IP 

Other (to be specified on the eCRF)
Subjects who are permanently discontinued from IP will be encouraged to continue participation 
in the study without IP administration in order to complete all remaining required study 
assessments including efficacy evaluations.  Subjects who decline further participation in the 
study should complete the early termination visit, and follow up visit assessments.  Subjects who 
discontinue early from IP and/or study participation will not be replaced.
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 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 

Physician decision

Withdrawal by subject 

Death

Lost to follow-up

Other (to be specified on the eCRF)
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The reason for study discontinuation should be recorded in the eCRF and in the source 
documents.  Because follow-up of subjects who discontinue from the study prematurely is of 
particular importance, every attempt should be made to collect all or specific final data on a 
discontinued subject.
11.3.
Emergency Contact
In emergency situations, the Investigator should contact the responsible Clinical Research
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, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page). This global 
Emergency Call Center is available 24 hours a day and 7 days a week. The representatives are 
responsible for obtaining your call-back information and contacting the on-call Celgene/contract 
research organization Medical Monitor, who will then contact you promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls. 
11.4.
Emergency Identification of Investigational Products
The blind must not be broken during the course of the study unless in the opinion of the 
Investigator, it is absolutely necessary to safely treat the subject.  If it is medically imperative to 
know what IP the subject is receiving, IP should be temporarily discontinued if, in the opinion of 
the Investigator, continuing IP can negatively affect the outcome of the subject’s treatment.
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 IRT by using an 
emergency unblinding personal identification number (PIN), and the Investigator should call IRT 
for unblended dose information.
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12.
REGULATORY CONSIDERATIONS
12.1.
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 Celgene, its authorized representative,
and Investigator abide by Good Clinical Practice (GCP), as described in International Council on 
Harmonisation (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.
12.2.
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations.  Celgene 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 Celgene 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 Celgene on public registry websites) is considered Celgene confidential 
information.  Only information that is previously disclosed by Celgene on a public registry 
website may be freely disclosed by the Investigator or its institution, or as outlined in the Clinical 
Trial Agreement.  Celgene 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 Celgene.  Information proposed for posting on the Investigator’s or their 
institution’s website must be submitted to Celgene 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, Celgene 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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12.3.
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 the study subject must be maintained in the Investigator’s 
study files and a copy given to the study subject.
12.4.
Confidentiality
Celgene 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). Celgene requires 
the Investigator to permit Celgene'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.
12.5.
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene 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.
12.6.
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 Celgene or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 
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Celgene 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 Celgene and the 
IRB/EC prior to use.  
12.7.
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.
12.8.
Termination of the Study
Celgene 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 Celgene 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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13.
DATA HANDLING AND RECORDKEEPING
13.1.
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.
13.2.
Data Management
Data will be collected via CRF and entered into the clinical database per Celgene 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.
13.3.
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, Celgene, 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 Celgene 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 Celgene prior to destruction of any 
records. If the Investigator is unable to meet this obligation, the Investigator must ask Celgene 
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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14.
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by Celgene or its authorized representative
for compliance with applicable government regulations with respect to current GCP and SOPs.
14.1.
Study Monitoring and Source Data Verification
Celgene 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 
Celgene 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 Celgene 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.
14.2.
Audits and Inspections
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within Celgene.  Representatives of this unit will conduct audits of clinical research 
activities in accordance with Celgene SOPs, and/or Bristol Meyer Squibb 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 Celgene immediately.
14.3.
Investigational Medicinal Product Quality Issues
Issues that call into question investigational medicinal product (IMP) safety, purity, potency, 
quality and identity (e.g., evidence of suspected tampering of product) must be reported as soon 
as possible to your study Clinical Trial Monitor and/or Clinical Trial Manager or designee. 
Report an issue or concern with all sponsor supplied IMP,  non-investigational medicinal product 
(NIMP) or auxiliary medicinal product (AxMP), suspected to have occurred before the product 
was transferred to the responsibility of the investigational site (eg, during manufacturing, 
packaging and labeling, storage, and/or distribution).
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This includes suspected quality issues of components co-packaged with the drug, labelling, and 
IMP device/drug combination products, and medical devices. 
In the event of a suspected product quality issue, the immediate action to be taken by site is to 
quarantine the affected product. Do not dispose of the product unless retention presents a risk to 
personnel (eg, cytotoxic, risk of injury from broken glass or sharps).
When reporting, provide as much product information as possible. Suspected IMP quality issues 
will be investigated and a response will be provided back to the investigational site.
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15.
PUBLICATIONS
As described in Section 12.2, all protocol- and amendment-related information, with the 
exception of the information provided by Celgene on public registry websites, is considered 
Celgene confidential information and is not to be used in any publications.  Celgene protocol-
related information proposed for use in a publication must be submitted to Celgene for review 
and approval, and should not be utilized in a publication without express written approval from 
Celgene, or as described in the Clinical Trial Agreement.
Celgene will ensure Celgene-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 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 external authorship, as well as selection of first authorship, will be based on 
several considerations, including, but not limited to, contribution to protocol development, study 
recruitment, data quality, participation in data analysis, participation in study steering committee 
(when applicable) and contribution to abstract, presentation and/or publication development.
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16.
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Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, 
double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). Br J 
Dermatol. 2020 Sep 30.
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Thoracic Society Conference. 2010 May 14-19; New Orleans, LA; USA: Abstract 6644.
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Yosipovitch G, Reaney M, Mastey V, Ecket L, Abbe A, Nelson L, et al. Peak Pruritus Numerical 
Rating Scale: psychometric validation and responder definition for assessing itch in moderate
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APPENDIX A. TABLE OF ABBREVIATIONS
Table 6:
Abbreviations and Specialist Terms
Abbreviation or 
Specialist Term
Explanation
AD 
Atopic dermatitis
ADL
Activity of daily life 
ADAs
Anti-drug antibodies
AE
Adverse event
AESI
Adverse events of special interest
ALT
Alanine aminotransferase (SGPT)
aPTT
Activated partial thromboplastin time
AST
Aspartate aminotransferase (SGOT)
AxMP
Auxiliary medicinal product
AUC
Area under the curve
β-hCG
β-subunit of human chorionic gonadotropin
BSA
Body surface area
CCL17
Chemokine (C-C motif) ligand 17
CCL18 
Chemokine (C-C motif) ligand 18 
CI
Confidence interval
Cmax
Maximum plasma concentration of drug
CMH
Cochran-Mantel-Haenszel
COVID
Corona virus disease 
CRF
Case report form
CRO
Contract research organization
CPK
Creatine phosphokinase
CRP
C reactive protein
CRS
Clinical research scientist
Ctrough
Serum trough concentration
DLQI
Dermatology Life Quality Index 
DMC
Data Monitoring Committee
DNA
Deoxyribonucleic acid
EASI
Eczema Area and Severity Index
EASI-50
Improvement of at least 50% in Eczema Area and Severity Index
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Table 6:
Abbreviations and Specialist Terms (Continued)
Abbreviation or 
Specialist Term
Explanation
EASI-75
Improvement of at least 75% in Eczema Area and Severity Index
EASI-90
Improvement of at least 90% in Eczema Area and Severity Index
EC
Ethics Committee
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
ELISA 
Enzyme-linked immunosorbent assay
EoE
Eosinophilic esophagitis
EOT
End of treatment
E/R
Exposure/response
ET
Early Termination 
Fc
Fragment, crystallizable
FCBP
Females of childbearing potential
FDA
Food and Drug Administration
GCP
Good Clinical Practice
HADS
Hospital Anxiety and Depression Scale
HBcAb
Hepatitis B core antibody
HBsAg 
Hepatitis B surface antigen
HBV
Hepatitis B virus 
Hct 
Hematocrit
HCV
Hepatitis C virus
Hgb 
Hemoglobin
HIV
Human immunodeficiency virus
ICF
Informed consent form
ICH
International Council on Harmonisation
IFN-y
Interferon gamma
IgE
Immunoglobulin E
IgG1κ
Immunoglobulin G1 Kappa
IGRA
Interferon gamma release assay
IL
Interleukin
IL-4
Interleukin-4 
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Table 6:
Abbreviations and Specialist Terms (Continued)
Abbreviation or 
Specialist Term
Explanation
IL-4R
Interleukin-4 receptor
IL-5
Interleuikin-5 
IL-13
Interleukin-13 
IL-13Rα1
IL-13 receptor alpha 1
IL-13Rα2
IL-13 receptor alpha 2 
IL-22
Interleukin-22
IMP
Investigational medicinal product
IND
Investigational New Drug
INR
International normalized ratio
IP
Investigational product
IRB
Institutional Review Board
IRT
Interactive Response Technology
ISR
Injection site reaction
IV
Intravenous
IUD
Intrauterine device 
IUS
Intrauterine hormone-releasing system
K-M
Kaplan-Meier
LOCF 
Last observation carried forward
mAb
Monoclonal antibody
MAR
Missing at random
MCH
Mean corpuscular hemoglobin
MCHC
Mean corpuscular hemoglobin concentration
MCV
Mean corpuscular volume
MedDRA
Medical Dictionary for Regulatory Activities
mITT
Modified intent to treat
MI
Multiple imputation
MOA
Mechanism of action
NIMP
Non-investigational medicinal product
NOAEL
No observed adverse effect level
NRS
Numeric Rating Scale
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Table 6:
Abbreviations and Specialist Terms (Continued)
Abbreviation or 
Specialist Term
Explanation
PARC
Pulmonary and activation-regulated chemokine
PD
Pharmacodynamics
PFS
Pre-filled syringe
PK
Pharmacokinetics
POEM
Patient Oriented Eczema Measure
PT
Prothrombin time
QOL
Quality of life
QW
Once weekly
Q2W
Every other week
RBC
Red blood cell count
RNA
Ribonucleic acid
RoW
Rest of world
SAE
Serious adverse event
SAP
Statistical analysis plan
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
SC
Subcutaneous
SCORAD
SCORing Atopic Dermatitis Index
SD
Standard deviation
SE
Standard error
SGOT
Serum glutamic oxaloacetic transaminase 
SGPT
Serum glutamic pyruvic transaminase
SI
Standard International System of Units
SMT
Safety Management Team
SOP
Standard operating procedure
SUSAR
Suspected unexpected serious adverse reaction
t1/2
Half-life
TARC
Thymus- and activation-regulated chemokine
TB
Tuberculosis
TEAE
Treatment emergent adverse event
TCI
Topical calcineurin inhibitor
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Table 6:
Abbreviations and Specialist Terms (Continued)
Abbreviation or 
Specialist Term
Explanation
TCS
Topical corticosteroid
Th2
Type 2 T helper
tmax
Time to the observed maximum concentration
ULN
Upper limit of normal
US
United States 
vIGA-AD
Validated Investigator Global Assessment for Atopic Dermatitis
WBC
White blood cell count
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APPENDIXB. HANIFIN/RAJKA DIAGNOSTIC CRITERIA FOR 
ATOPIC DERMATITIS
Diagnosis of atopic dermatitis requires the presence of at least 3 basic features plus 3 or more
minor features as listed below:
Basic Features:Must have three or more basic features:
Pruritus
Typical morphology and distribution
Flexural lichenification or linearity in adults
Chronic or chronically-relapsing dermatitis
Personal or family history of atopy (asthma, allergic rhinitis, atopic dermatitis)
Minor Features:  Plus, three or more minor features
Xerosis
Ichthyosis, palmar hyperlinearity, or 
keratosis pilaris
Immediate (type 1) skin-test reactivity
Elevated serum IgE
Early age of onset
Tendency toward cutaneous infections 
(especially Staph. aureus and Herpes
simplex)/impaired cell-mediated immunity
Tendency toward non-specific hand or foot 
dermatitis
Nipple eczema
Cheilitis
Recurrent conjunctivitis
Dennie-Morgan infraorbital fold
Keratoconus
Anterior subcapsular cataracts
Orbital darkening
Facial pallor/facial erythema
Pityriasis alba
Anterior neck folds
Itch when sweating
Intolerance to wool and lipid solvents
Perifollicular accentuation
Food intolerance
Course influenced by environmental or 
emotional factors
White dermographism/delayed blanch
Reference: (Hanifin, 1980
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APPENDIX C. VALIDATED INVESTIGATOR GLOBAL ASSESSMENT 
SCALE FOR ATOPIC DERMATITIS (V-IGA™)
Instructions: The IGA score is selected using the descriptors below that best describe the overall 
appearance of the lesions at a given time point. It is not necessary that all characteristics under 
Morphological Description be present.
Score
Morphological Description
0-Clear
No inflammatory signs of atopic dermatitis (no erythema, no 
induration/papulation, no lichenification, no oozing/crusting). Post-inflammatory 
hyperpigmentation and/or hypopigmentation may be present.
1-Almost clear
Barely perceptible erythema, barely perceptible induration/papulation, and/or 
minimal lichenification.  No oozing or crusting.
2-Mild
Slight but definite erythema (pink), slight but definite induration/papulation, 
and/or slight but definite lichenification.  No oozing or crusting.
3-Moderate
Clearly perceptible erythema (dull red), clearly perceptible 
induration/papulation, and/or clearly perceptible lichenification. Oozing and 
crusting may be present.
4-Severe
Marked erythema (deep or bright red), marked induration/papulation, and/or 
marked lichenification. Disease is widespread in extent. Oozing or crusting may 
be present.
Copyright ©2017 Eli Lilly and Company - Used with the permission of Eli Lilly and Company under a Creative 
Commons Attribution-NoDerivativ es 4.0 International License - https://creativecommons.orq/licenses/by-nd/4.0/
Reference (Simpson, 2020)
1. In indeterminate cases, please use extent to differentiate between scores. For example: 
Patient with marked erythema (deep or bright red), marked papulation and/or marked 
lichenification that is limited in extent, will be considered "3- Moderate".
2. Excoriations should not be considered when assessing disease severity.
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APPENDIX D. ECZEMA AREA AND SEVERITY INDEX (EASI)
The EASI scoring system uses a defined process to grade the severity of the signs of eczema and 
the extent affected:
1. Select a body region
Four body regions are considered separately:

Head and neck

Trunk (including the genital area)

Upper extremities

Lower Extremities (including the buttocks)
2. Assess the extent of eczema in that body region
Each body region has potentially 100% involvement. Using the table below, give each 
respective body region a score of between 0 and 6 based on the percentage involvement. 
Precise measurements are not required.
% involvement
0
1 - 9%
10 - 29%
30 - 49%
50 - 69%
70 - 89%
90 - 100%
Region score
0
1
2
3
4
5
6
3. Assess the severity of each of the four signs in that body region:

Erythema

Edema/papulation

Excoriation

Lichenification
4. Grade the severity of each sign on a scale of 0 to 3:
0
None
Take an average of the severity across the involved region.
Half points (1.5 and 2.5) may be used. 0.5 is not permitted – if a sign is present 
it should be at least mild (1)
Palpation may be useful in assessing edema/papulation as well as 
lichenification
1
Mild
2
Moderate
3
Severe
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APPENDIX D. ECZEMA AREA AND SEVERITY INDEX (EASI)
(CONTINUED)
5. The assessed parameters are inserted into a table (example shown below for age≥8 
years). The final EASI score ranges from 0 to 72.
Body region
Erythema
Edema/
papulation
Excoriation
Lichenification
Area
score
Multiplier
Score
Head/neck
(             +
+
+
)
X
X 0.1
Trunk
(             +
+
+
)
X
X 0.3
Upper
extremities
(             +
+
+
)
X
X 0.2
Lower
extremities
(             +
+
+
)
X
X 0.4
The final EASI score is the sum of the 4 region scores
(0-72)
EASI guidance v3 January 2017 (www.homeforeczema.org)
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APPENDIX E. BODY SURFACE AREA
Determine BSA using the subject handprint = 1% rule.
The handprint unit refers to the size of each individual subject’s hand with fingers adducted (eg 
in a closed position) measured from the wrist to the proximal interphalangeal (PIP) and thumb.
Estimate the number of handprint it takes to cover the affected AD area. Add up the number of
handprints to give a total estimate of the area covered in AD.
Below are estimates when entire areas of the body are covered:
Table 7:
Handprint Assessment of BSA
Body Region 
Total Number of Handprints 
Estimated per Body Region
Total Estimated BSA% per 
Body Region
Head and Neck
10
10%
Upper Limbs
20
20%
Trunk (including axillae and
groin/genitals)
30
30%
Lower Limbs (including buttocks)
40
40%
Additional guidance:

When many small lesions are present, lesions may be counted in combination to 
achieve the handprint 1% measure. 

Areas of a lesion that have cleared should not be counted

Final BSA% calculation should be cross checked against across other efficacy 
parameters (eg, % involvement assessed via during EASI) to ensure consistency 
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APPENDIX F.
SCORING ATOPIC DERMATITIS INDEX
The SCORAD Index formula is: A/5 + 7B/2 + C.
A=Extent (maximum score of 100%)
To determine extent of AD, rule of 9 is used to calculate body surface area affected by AD as a 
percentage of the whole-body surface area. Body surface area as percentage of total body surface 
area for each body region is as follows:

Head and neck 9%;

Upper limbs 9% each;

Lower limbs 18% each;

Anterior trunk 18%;

Back 18%;

1% for genitals.
The score for each body region is added up to determine the BSA affected by AD.
B=Severity (maximum score of 18)
A representative area of AD is selected. In this area, the severity of each of the following signs is 
assessed as none (0), mild (1), moderate (2) or severe (3).

Erythema (reddening);

Edema (swelling)/papulation;

Oozing/crusting;

Excoriation (scratch marks);

Skin thickening (lichenification);

Xerosis (dryness) (this is assessed in an area where there is no inflammation).
The severity scores are added together.
C= Subjective Symptoms (maximum score of 20)
Subjective symptoms (ie, itch and sleep loss) are each scored by the subject using a visual analog 
scale (VAS) where “0” is no itch (or no sleep loss) and “10” is the worst imaginable itch (or 
sleep loss). 
The value for each should reflect the average on a 10-point scale for the last 3 days/nights. These 
scores are added together.
SCORAD Total Score: The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 
+ C (can range from 0 to 103).
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