A Phase 3, Multicenter, Multinational, Open-Label Extension Study to Evaluate the Long-Term Safety of CC-93538 in Adult and Adolescent Subjects With Eosinophilic Esophagitis
Phase: PHASE3
Conditions: Eosinophilic Esophagitis
Sponsor: Celgene

Official Title of Study: 
A Phase 3, Multicenter, Multinational, Open-Label Extension Study 
to Evaluate the Long-Term Safety of CC-93538 in Adult And 
Adolescent Subjects with Eosinophilic Esophagitis 
NCT Number: NCT04991935 
Document Date (Date in which document was last revised): 30 Jun 2023 

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
1
A PHASE 3, MULTICENTER, MULTINATIONAL, OPEN-LABEL EXTENSION STUDY 
TO EVALUATE THE LONG-TERM SAFETY OF CC-93538 IN ADULT AND 
ADOLESCENT SUBJECTS WITH EOSINOPHILIC ESOPHAGITIS
PROTOCOL NUMBER:
CC-93538-EE-002
COMPOUND NUMBER:
CC-93538 (BMS-986355)
DATE FINAL:
26 Feb 2021
AMENDMENT No. 0.1 DE DATE:
01 Dec 2021
AMENDMENT 1.0 DATE:
10 May 2022
ADMINISTRATIVE LETTER No. 01 DATE:
06 Dec 2022
AMENDMENT 2.0 DATE:
30 Jun 2023
EudraCT NUMBER:
2020-004335-24
EU TRIAL NUMBER
2023-506278-10-00
IND NUMBER:
119240
SPONSOR NAME/ADDRESS:
Celgene International II Sàrl
Route de Perreux 1
2017 Boudry 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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CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION 
24/7 PPD Medical Monitor Safety Hotline
North American Regional Contact
EMEA & APAC Regional Contact
Phone: +1-888-483-7729
Phone: +44-122-337-4240
Fax: +1-888-529-3580
Fax: +44-122-337-4102
Sponsor Clinical Trial Physician 
Contact Information:
Name:
Title:
Address: Bristol-Myers Squibb
                3401 Princeton Pike
                Lawrenceville, NJ 08648
Phone:
E-mail:
The back-up 24-hour global emergency contact call center should only be used if you are not 
able to reach the PPD Medical Monitor(s) or Clinical Trial Physician(s) or designee for 
emergency calls.
Back-up 24-hour Global Emergency Contact Call Center: +1-877-501-7738
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Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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SPONSOR:  CELGENE INTERNATIONAL II SÀRL
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Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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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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Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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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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CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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OVERALL RATIONALE FOR PROTOCOL AMENDMENT 2:
Protocol Amendment 2 is being implemented to support the introduction of a new autoinjector (AI) 
presentation for administration of CC-93538 (BMS-986355) as a weekly subcutaneous (SC) dose 
by a 
 injection at a concentration of 
 mg/mL. The details on the transition of current 
and new subjects to the new AI presentation, timing of visits, and the inclusion of the AI 
Administration Questionnaire are incorporated in the body of the protocol. This amendment also 
includes the preliminary results from Study IM042-003, a single dose pharmacokinetic study 
comparing the AI and pre-filled syringe (PFS) presentations. 
The following summary of changes outlines the revisions to the various sections of Protocol 
Amendment 2.
This amendment includes changes from approved Administrative Letter 01, and those changes are 
not listed in the table below. The Protocol Summary was updated to reflect changes made in the 
body of the protocol.
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 2
Section Number & 
Title
Description of Change
Brief Rationale
Throughout 
Pre-filled syringe (PFS) has been 
replaced with autoinjector (AI) in 
multiple places throughout the 
protocol.
Upon the implementation of 
this amendment, the 
CC-93538 360 mg SC dose
will be administered via a
new AI presentation.
Section 1.1, Disease 
Background: 
Eosinophilic 
Esophagitis
Deleted part of a sentence that is no
longer accurate and included a new
statement for Food and Drug 
Administration and European 
Medicines Agency approval of 
dupilumab as new treatment for 
eosinophilic esophagitis (EoE).
Updated the background 
information to include new 
available treatments for EoE.
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Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 2
Section Number & 
Title
Description of Change
Brief Rationale
Section 1.2.2, Clinical 
Studies
Updated the list of CC-93538 
clinical studies with results 
available.
Study CC-93538-CP-002 was 
completed with the results 
available in the clinical study 
report.
These changes include the 
preliminary results of Phase 1 
Study IM042003, which 
provides the pharmacokinetic 
(PK) comparability, safety, 
tolerability, and 
immunogenicity of 
 
subcutaneous (SC) injections 
of CC-93538 administered 
using an AI versus PFS. 
Section 1.2.2.6, Phase 
1 Study, IM042-003
Section 1.3.3, 
Rationale for Dose, 
Schedule and Regimen 
Selection
A new section was added providing 
background information and data 
regarding Study IM042-003. 
Section updated to include the 
rationale for the introduction of the 
 AI 
presentation.
To include the preliminary 
results of Phase 1 Study 
IM042-003 Part 1, which 
provides PK comparability, 
safety, tolerability, and 
immunogenicity of 
 SC 
injections of CC-93538 
administered using an AI 
versus PFS. 
The results of Study IM042-
003 support the introduction 
of the 
 AI presentation 
in Protocol Amendment 2.
Section 1.2.2.2, Phase 
2 Study, CC-93538-
AD-001
A new section was added to 
provide information on Study CC-
93538-AD-001. 
To include a brief description 
of the Phase 2 Study 
CC-93538-AD-001 evaluating
CC-93538 for 
moderate-to-severe atopic 
dermatitis.
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Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
9
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 2
Section Number & 
Title
Description of Change
Brief Rationale
Section 1.3.2, 
Rationale for the Study 
Design
Advisory panel of patients, 
caregivers, and feedback from the 
members of the EoE community 
was consulted for input on protocol 
design and development of patient-
facing materials and recruitment 
initiation.
To provide information on the 
involvement of patients, 
caregivers, and patient 
advocacy groups in the study 
design/implementation
process. 
Table 1, Study 
Objectives
Table 2, Study 
Endpoints
A new exploratory objective and 
endpoint has been added to estimate 
the frequency of successful self-
administration of CC-93538 by AI 
under supervised (in-clinic) and 
unsupervised (at home) conditions.
To account for the change in 
the presentation of 
administration of CC-93538 
from PFS to AI.
Table 2, Study 
Endpoints
A new exploratory endpoint has 
been added to estimate the 
proportion of subjects previously 
treated with CC-93538 in Study 
CC-93538-EE-001 and with peak 
esophageal eosinophil count 
≤6/high power field (hpf) at open 
label extension (OLE) baseline who 
continue to have a peak esophageal 
eosinophil count ≤ 6/hpf throughout 
the OLE study.
To analyze the trend of peak 
eosinophil count in subjects 
previously treated with 
CC-93538 in Study 
CC-93538-EE-001 with 
histologic response at OLE 
baseline who continue to 
demonstrate response in the 
OLE study, as an assessment 
of durability of response.
Table 2, Study 
Endpoints
Added the time point of Week 104 
for evaluation of clinical response 
endpoints 
 
.
To enable further evaluation 
of EoE symptoms with the 
mDSD at the end of Year 2.
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Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 2
Section Number & 
Title
Description of Change
Brief Rationale
Section 3.2.1, Open-
label Treatment Period
Table 3, Table of 
Events for the Open-
label Extension Study
Section 6.2, Open-label 
Extension Treatment 
Period
Increased the maximum acceptable 
interval between the last dose of 
investigational product (IP) in 
Study CC-93538-EE-001/CC-
93538-DDI-001 to the first dose in 
the OLE study (increased from 14 
to 21 days).  
Subjects will not be allowed to be 
enrolled in the study if there will be 
a delay of > 21 days from 
CC-93538 dosing in Study 
CC-93538-EE-001 or in Study 
CC-93538-DDI-001, unless 
discussed with the Medical 
Monitor.
Accounting for unavoidable 
situations that may cause 
delays in the first dose in OLE 
(eg. coronavirus disease 2019
restrictions, unavailability of 
IP supplies, scheduling issues)
and for increased flexibility 
for sites to enroll subjects on 
this study and receive 
CC-93538.
Section 3.2.3, 
Worsening of EoE 
Symptoms or Lack of 
Improvement
Removed the requirement to 
discontinue study treatment for 
subjects who demonstrate persistent 
lack of improvement or worsening 
of EoE symptoms. The text has 
been updated to state that these 
subjects should be evaluated to 
determine if the continuation of 
study treatment is appropriate.  
For clarification purposes.
Section 3.2.4, Planned 
Database Locks
New section added for planned 
database locks.
Section added to provide 
information on the multiple 
database locks planned 
throughout the study.
Section 3.3, Study 
Duration in Subjects
In Japan, subjects may continue in 
the study until marketing launch is 
obtained in the country or the 
Sponsor discontinues the study, 
whichever comes first.
In Japan, the term “this study” in 
this protocol will automatically be 
replaced with “post-marketing 
clinical study” on and after the date 
of marketing approval.
To incorporate 
country-specific requirements.
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Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 2
Section Number & 
Title
Description of Change
Brief Rationale
Section 4.2, Inclusion 
Criteria 4)
The definition of female of 
childbearing potential was updated 
to include those who have not 
undergone a bilateral 
salpingectomy.
For clarification purposes.
Section 4.3, Exclusion 
Criteria 1) and 4)
Section 8.2, Prohibited 
Concomitant 
Medications and
Procedures

Added Schatzki's rings and a 
history of fundoplication as 
exclusion criteria, and updated
nomenclature for eosinophilic 
gastroenteritis to eosinophilic
gastritis and/or duodenitis.

Included JAK inhibitors and
phosphodiesterase-4 inhibitors 
as examples of 
immunomodulating drugs and 
as prohibited concomitant 
medications on study.
For clarification purposes.
Table 3, Table of 
Events for the Open-
label Extension Study

Included an additional AI 
Administration Visit for 
switching to the new IP 
presentation.

Footnote y added to provide the 
window for the First AI 
Administration Visit.

AI Administration 
Questionnaire updated with 
additional time points.

Footnote w has been updated to 
include the time points for the
AI Administration 
Questionnaire collection (as 
applicable).

This First AI 
Administration Visit is 
being added to expedite 
the switch to the new AI 
presentation for subjects 
whose next scheduled 
visit is not within 4 weeks 
of the Protocol 
Amendment 2
implementation and IP 
availability at the site.

To denote the time points 
when the AI 
Administration 
Questionnaire is
performed.
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Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 2
Section Number & 
Title
Description of Change
Brief Rationale
Table 3, Table of 
Events for the Open-
label Extension Study
Section 6.2, Open-label 
Extension Treatment 
Period
Section 6.4.2.1, 
Modified Daily 
Symptom Diary 
(mDSD)

Additional time points added for 
mDSD collection on the 28 days 
prior to the Quarterly (Q)4 Visit 
at the end of Year 2 (Week 
104).  

Phone call reminders added 
within a couple days prior to 
Week 100 and prior to Week 
102.

Modified 2 footnotes (l and m) 
regarding timing for phone call 
reminders to complete the 
mDSD and the time points for 
collection of mDSD at the end 
of Year 2 for consistency with 
Table 3. 
To continue collection of the 
mDSD at the end of Year 2 to 
assess the effects of CC-
93538 on clinical response 
longer term.
Table 3, Table of 
Events for the Open-
label Extension Study

Additional time points added for 
serum CC-93538 PK 
assessment at Q1 and Q3 Visits.

Additional time points added for 
serum antibodies to CC-93538 
assessment at Week 16 and 36 
of Year 1 and at the Q1 and Q3 
Visits at Year 2 and beyond.
To acquire more data on the 
drug product presentations.
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Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 2
Section Number & 
Title
Description of Change
Brief Rationale
Section 6.2, Open-label 
Extension Treatment 
Period

Discussion with Medical 
Monitor was added if there is a 
delay of > 21 days from 
CC-93538 dosing in Study 
CC-93538-EE-001 or in Study 
CC-93538-DDI-001 to 
enrollment in this study.

Revised and provided additional
guidance on the baseline 
esophagogastroduodenoscopy 
(EGD) at Day 1.

Time points for the AI 
Administration Questionnaire 
were removed from this section
for simplification and replaced 
with reference to the Table of 
Events.

Change in the number of 
days to align with the 
longest window allowed 
between dosing in the CC-
93538-EE-001/CC-93538-
DDI-001 studies.

To provide further 
clarification on the timing 
of the baseline EGD 
procedure in the OLE 
study.

Overall simplification of 
text and consolidation of 
information to the Table 
of Events.
Section 6.2.2, First 
Autoinjector
Administration Visit
A new section for the First AI 
Administration Visit and the 
required evaluations has been 
added. 
To include the assessments 
that will be conducted in the 
First AI Administration Visit.
Section 6.4.2.1, 
Modified Daily 
Symptom Diary 
(mDSD)
 
 
 
 
 
Section 6.4.2.7, 
Worsening of EoE 
Symptoms, EoE Flare, 
the EoE Flare 
Assessment Visit, and 
Lack of Improvement
Removed the requirement to 
discontinue study treatment for 
subjects who demonstrate persistent 
lack of improvement or worsening 
of EoE symptoms. The text has 
been updated to state that these 
subjects should be evaluated to 
determine if the continuation of 
study treatment is appropriate.    
For clarification purposes.
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Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 2
Section Number & 
Title
Description of Change
Brief Rationale
Section 6.9.2, 
Autoinjector (AI)
Administration 
Questionnaire/PFS 
Administration 
Questionnaire
This section has been revised to 
align with the introduction of the 
AI presentation and a switch to the 
AI Administration Questionnaire
going forward. 
The introduction of a new AI 
presentation requires an AI 
Administration Questionnaire 
to evaluate the successful self-
administration of CC-93538 
by the AI.
Section 6.6.1, Serum 
CC-93538 Assessments
Statement added, “ in the event 
dosing occurs during a non-clinic 
visit day, it is still acceptable to 
obtain the serum samples”.  
For clarification purposes.
Section 7.1, 
Description of 
Investigational 
Product(s)
CC-93538 AI information has been 
provided.
Treatment information for the 
AI has been added.
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Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 2
Section Number & 
Title
Description of Change
Brief Rationale
Section 7.2, Treatment 
Administration and 
Schedule

AI implementation details have 
been added for subjects
beginning the OLE study with 
the AI and for ongoing subjects
switching to the AI, with
requirements for the first dose
of the AI and completion of the 
AI Administration 
Questionnaire.  Further, 
requirements for a First AI 
Administration Visit are noted.

Additionally, text is included to 
clarify that if IP is not available 
on site at the time of Protocol 
Amendment 2 site approval, 
then subjects should continue 
receiving the 
 
weekly SC injection using the 
 PFS presentation, 
until the availability of the new 
IP (AI) presentation. Subjects 
who self-administer with the 
PFS presentation should 
continue to complete the PFS 
Administration Questionnaire 
until the switch to the new AI 
presentation.

To provide clarification as 
to which assessments will 
be conducted in the First 
AI Administration Visit.

To provide clarification on 
which IP presentation 
should be provided to 
subjects and the 
questionnaire that should 
be completed in the event 
the IP (AI) is not available 
on site at the time of 
Protocol Amendment 2 
site approval.
Section 9.7, Safety 
Analysis
Updated information based on the 
AI administration has been added.
Updated per changes in 
Protocol Amendment 2.
Section 9.9.1,
Pharmacokinetics, 
Pharmacodynamics and 
Exposure-Response
Additional text added to describe 
how Serum trough concentrations 
(Ctrough) of CC-93538 will be 
summarized for subjects in the OLE 
Study, CC-93538-EE-002 and 
subjects transitioning from the 
Phase 1 Study, CC-93538-DDI-
001.
For clarification purposes. 
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Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 2
Section Number & 
Title
Description of Change
Brief Rationale
Section 10.6, Adverse 
Events of Special 
Interest
Adverse events of special interest 
(AESIs) will be reported to the 
electronic data capture and 
identified by the Sponsor 
programmatically.
Updates made to include 
Sponsor capture and review of 
AESIs in addition to the 
Investigator. 
Section 11.1, 
Treatment 
Discontinuation
Section 11.2, Study 
Discontinuation
Clarified that protocol deviation 
that may impact subject safety is a 
sufficient reason for permanent 
discontinuation from CC-93538.
For clarification purposes.
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Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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PROTOCOL SUMMARY
Study Title
A Phase 3, Multicenter, Multinational, Open-label Extension Study to Evaluate the Long-term 
Safety of CC-93538 in Adult and Adolescent Subjects with Eosinophilic Esophagitis
Indication
CC-93538, also known as BMS-986355 (nonproprietary name, cendakimab), 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).  Eosinophilic esophagitis (EoE) is a chronic immune/antigen-mediated esophageal 
disease characterized clinically by symptoms related to esophageal dysfunction and histologically 
by eosinophil-predominant inflammation, and IL-13 has been shown to be a key driver of disease 
pathology in patients with EoE.
The Phase 3 program will include a multicenter, multinational, randomized, double-blind, placebo-
controlled 24-week induction and 24-week maintenance study to evaluate the efficacy and safety 
of CC-93538 in adult and adolescent subjects with eosinophilic esophagitis (EoE; Study 
CC-93538-EE-001) with a separate, optional Open-label Extension study (OLE; Study CC-93538-
EE-002). 
Additionally, a Phase 1, open-label, single-sequence study will be employed to evaluate potential 
disease-mediated drug-drug interactions with selected cytochrome P450 (CYP) substrates and to 
assess the safety of CC-93538 with or without CYP substrates in adult subjects with active 
eosinophilic esophagitis receiving CC-93538 (Study CC-93538-DDI-001). 
Subjects participating in Study CC-93538-EE-001 or Study CC-93538-DDI-001 will be offered
the opportunity to enroll in the OLE Study CC-93538-EE-002. Globally, the Phase 3 studies will 
include subjects who have had an inadequate response to corticosteroid therapy or are intolerant 
to corticosteroid therapy as well as subjects who are naïve or have had an adequate response to 
corticosteroid therapy.  However, in Germany, Spain, and the United Kingdom, only subjects who 
have had an inadequate response to corticosteroid therapy or are intolerant to corticosteroid therapy 
(as defined in Protocol CC-93538-EE-001) will be enrolled in the studies.
Results of the Phase 2 Study, RPC02-201, in adult subjects with EoE showed that administration 
of CC-93538 180 mg and 360 mg subcutaneously (SC) weekly for 16 weeks reduced the mean
esophageal eosinophil count (the primary endpoint) and improved other inflammatory parameters.
A greater reduction in dysphagia symptoms was observed with the CC-93538 360 mg dose
although it did not reach statistical significance. The study also demonstrated the safety and 
tolerability of CC-93538 in adult subjects with symptomatic EoE who were treated with one of 
2 dose levels (CC-93538 180 mg or 360 mg SC) compared to placebo.  CC-93538 was generally 
safe and well tolerated for up to 68 weeks of treatment in Study RPC02-201 (including data from 
a 52-week CC-93538 Open-label Extension).  These data support the continued development of 
CC-93538 as a novel treatment for EoE.  The single pivotal Phase 3 study is designed to confirm
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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and extend the findings obtained from the positive Phase 2 study with CC-93538, and the OLE 
study will continue to investigate the long-term safety profile of CC-93538 in adult and adolescent 
subjects with EoE.
Objectives (Primary and Secondary)
Primary Objective

To evaluate the long-term safety and tolerability of CC-93538 in subjects with EoE
Secondary Objective

To characterize the immunogenicity profile of CC-93538 following long-term treatment
See Section 2 for a complete list of study objectives, including all exploratory objectives.
Study Endpoints (Primary and Secondary)
Primary Endpoint

Safety and tolerability of long-term treatment with CC-93538 evaluated by the incidence, 
severity, and relationship to CC-93538 of adverse events (AEs), serious adverse events (SAEs), 
clinical laboratory abnormalities, changes in vital signs, and physical examination 
abnormalities.
Secondary Endpoint

Immunogenicity of CC-93538 assessed through the incidence of anti-drug antibodies to CC-
93538 including neutralizing antibodies when warranted.
See Section 2 for a complete list of study endpoints including all exploratory endpoints.
Study Design
The OLE study is a Phase 3, open-label, uncontrolled study to explore the long-term effects of 
treatment with CC-93538 360 mg SC once weekly in adult and adolescent subjects with EoE who 
had previously participated in the Induction and Maintenance Study, CC-93538-EE-001.  
Approximately, 259 of the 399 subjects aged 12 to 75 years and weighing ≥ 40 kg at the time of 
screening and initially randomized in Study CC-93538-EE-001 are expected to participate in the 
OLE study assuming an overall drop-out rate of 35% in Study CC-93538-EE-001.  Of these,
approximately 239 adults and approximately
adolescents aged 12 to 17 years at the time of 
screening in Study CC-93538-EE-001 are anticipated to enroll. 
In Austria, Germany, Spain, and Switzerland, adolescent subjects will not be enrolled.  Subjects 
participating in Study CC-93538-EE-001 who do not qualify for entry into the Maintenance Phase, 
including subjects who experience a severe EoE flare requiring endoscopic intervention and/or 
rescue therapy during the Induction Phase or subjects who complete Week 48 of the Maintenance 
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CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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Phase may be eligible.  In addition, subjects must have demonstrated sufficient investigational 
product (IP) compliance and must not have been permanently discontinued from IP in Study CC-
93538-EE-001 and, in the opinion of the Investigator, must have experienced no clinically 
significant AEs related to IP that would preclude further dosing. Additionally, approximately 
subjects aged 18 to 75 years initially enrolled in Study CC-93538-DDI-001 and who completed 
Period 2 of Study CC-93538-DDI-001 will be offered an opportunity to enroll in the OLE Study 
CC-93538-EE-002.
During the Open-label Treatment Period, all subjects will be administered CC-93538 at a dose of 
360 mg SC once weekly.  Clinical laboratory tests, vital signs, physical examinations (including 
height and weight), pregnancy tests, esophagogastroduodenoscopy (EGD), clinical symptom 
assessment, subject-reported outcomes, serum CC-93538 concentrations, serum antibodies to CC-
93538 (to monitor for immunogenicity), concomitant medications, AE assessments, and relevant 
biomarker measurements in tissue biopsy and blood samples will be performed in accordance with 
the Table of Events (Table 3).
Subjects may discontinue from the study at any time. Furthermore, subjects who demonstrate a 
persistent lack of improvement or worsening of EoE symptoms during the course of the study 
should be discontinued.  Subjects who discontinue the study at or after 2 years of participation (ie, 
the Quarterly 4 Visit in Year 2 [Week 104]) will complete an End of Treatment Visit within 2 
weeks after the final dose of CC-93538 and 2 Safety Follow-up Visits at 8 and 16 weeks, 
respectively, after the final dose of CC-93538 for the assessment of safety and clinical status. 
Subjects who discontinue the study before Week 104 will complete an Early Termination Visit.
The study will be conducted in compliance with International Council for Harmonisation (ICH) 
Good Clinical Practices (GCPs).
Study Population
The study population will consist of:

Male and female adult and adolescent subjects with EoE aged 12 to 75 years (inclusive, at the 
time of screening in Study CC-93538-EE-001) who have participated in the core Phase 3 
Induction and Maintenance Study, CC-93538-EE-001. Subjects who have completed Study 
CC-93538-EE-001 and subjects who do not meet entry criteria to the Maintenance Phase in 
Study CC-93538-EE-001, including subjects who have a severe EoE flare requiring 
endoscopic intervention and/or rescue therapy during Study CC-93538-EE-001 may be eligible 
to participate in the OLE study.

Male and female adult subjects with EoE aged 18 to 75 years (inclusive, at the time of screening 
in Study CC-93538-DDI-001) who have participated in Study CC-93538-DDI-001. Subjects 
who have completed Week 18/End of Study Treatment Visit of Period 2 may be eligible to 
participate in the OLE study.
Note:  In Study CC-93538-EE-001, countries or sites with local restrictions that prohibit 
enrollment of adolescents (aged 12 to 17 years inclusive) will only enroll subjects who are 18 years 
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CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
20
of age or older.  Enrollment of adolescent subjects will begin only after the applicable regulatory
requirements for enrolling subjects in that age group have been satisfied and the necessary health 
authority and Ethics Committee approvals have been granted.  Where national or regional 
guidelines for the definition of adolescence differ from the definition stated above, the national or 
regional guidelines may be used to determine eligibility.  In Austria, Germany, Spain, and 
Switzerland, adolescent subjects will not be enrolled.
Length of Study
Subjects will begin participation in the OLE study on OLE Day 1 and following completion of all 
baseline assessments (including those obtained from either the Study CC-93538-EE-001 Induction 
Phase Week 24 or Maintenance Phase Week 48 Visit, as applicable, or the Study CC-93538-DDI-
001 Week 18/End of Treatment Visit, as applicable) will receive the first OLE dose of CC-93538. 
Subjects will receive weekly doses of CC-93538 during the Open-label Treatment Period for a 
minimum of 2 years or as long as they are participating in the study, will complete an End of 
Treatment Visit within 2 weeks after the final dose, and will complete the 2 Safety Follow-up 
Visits at 8 and 16 weeks after the final dose. Subjects may participate in the Open-label Treatment 
Period as early as 24 weeks after beginning enrollment in the Induction Phase of the core Phase 3 
Study CC-93538-EE-001 or as late as following Week 48 of the core study.  
Additionally, subjects who complete Period 2 in Study CC-93538-DDI-001 may be eligible to 
participate in the Open-label Extension (OLE) study.
Individual subject participation in the OLE study will be for a minimum of 2 years but may extend 
for a longer duration. Where applicable per local or national regulations, subjects may continue 
in the study until marketing approval (or marketing launch in Japan) is obtained in the country or 
the Sponsor discontinues the study, whichever comes first.  In Japan, the term “this study” in this 
protocol will automatically be replaced with “post-marketing clinical study” on and after the date 
of marketing approval.
The End of Study is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up (the Final 16-week Safety Follow-up Visit), 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 pre-specified in the protocol, whichever is the later date.
Study Treatments
All subjects in the OLE study will receive CC-93538 360 mg SC once weekly. The dosing regimen 
for the OLE may be revised after results from the Induction and Maintenance Study, CC-93538-
EE-001, are available and the optimal dosing regimen is confirmed.  The CC-93538 360 mg SC 
dose will be administered by a 
 provided in a 
 autoinjector 
(AI) at a concentration of 
mg/mL. 
The original protocol required CC-93538 weekly SC dosing to be administered by 
 
of 
 mL each at a concentration of 
 mg/mL. With the implementation of Protocol 
Amendment 1 (dated 10 May 2022), all subjects in the study and any subjects newly entering the 
study began receiving a 
 pre-filled syringe (PFS) presentation. As 
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Final: 30 Jun 2023
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of Protocol Amendment 2, all subjects currently in the study and any new subjects entering the 
study will start receiving a 
 AI once Protocol Amendment 2 is 
implemented, informed consent is obtained, and IP is available on-site.  For currently enrolled 
subjects, a switch to the new AI presentation will occur at the next regularly scheduled study visit
or at a First AI Administration Visit in case the next scheduled protocol visit is not within 4 weeks 
of Protocol Amendment 2 site approval, once the IP is available on site. This First AI 
Administration Visit is added to expedite the switch to the new AI presentation.
Overview of Key Safety Assessments

Type, frequency, severity, seriousness, and relationship of AEs to IP

Clinically significant changes in vital signs, physical examinations, and laboratory findings 

Presence of and clinical effects of anti-drug antibodies (ADAs) including assessment of 
neutralizing antibodies if warranted
For additional details about key safety assessments, please refer to the Table of Events (Table 3).
Overview of Key Efficacy Assessments

Number of dysphagia days (DD) and modified Daily Symptom Diary (mDSD) composite score 
using the mDSD instrument

Enumeration of esophageal eosinophil count (peak esophageal eosinophil count) by analysis 
of hematoxylin and eosin (H&E) stained esophageal biopsies

EoE Endoscopic Reference Score (EREFS)

EoE histology scoring system (EoEHSS)
For additional detail about key efficacy assessments, please refer to the Table of Events (Table 3).
Statistical Methods
Analysis Population
The analysis population that will be used in the statistical analysis is the OLE population which 
consists of all subjects receiving at least one dose of IP during the OLE.  
The OLE population consists of subjects who are originally randomized to the 3 arms in 
CC-93538-EE-001: placebo in both the Induction Phase and the Maintenance Phase, CC-93538 
360 mg SC once weekly in the Induction Phase and CC-93538 360 mg SC once every other week 
in the Maintenance Phase, and CC-93538 360 mg SC once weekly in both the Induction Phase and 
the Maintenance Phase. These subjects can enter the OLE either: after completing Week 24 of the 
Induction Phase or after completing Week 48 of the Maintenance Phase.
Subjects will be analyzed based on the treatments received during the core Induction and 
Maintenance Study, CC-93538-EE-001, defined as:
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Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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
For subjects who enter OLE after completing Week 24 of the Induction Phase, based on the 
treatment(s) the subjects received in CC-93538-EE-001 before they enter OLE, there are 2
different cohorts: 

Cohort A:  Subjects receiving placebo in the Induction Phase but did not enter the 
Maintenance Phase (denoted as “PBO/-”)

Cohort B:  Subjects receiving CC-93538 360 mg SC once weekly in the Induction Phase 
but did not enter the Maintenance Phase (denoted as “360 mg QW/-”)

For subjects who enter after completing Week 48 of the Maintenance Phase, based on the 
treatment(s) the subjects received in CC-93538-EE-001 before they entered OLE, there are 3
different cohorts:

Cohort C:  Subjects receiving placebo in both the Induction Phase and the Maintenance 
Phase (denoted as “PBO/PBO”)

Cohort D:  Subjects receiving CC-93538 360 mg SC once weekly in the Induction Phase 
and CC-93538 360 mg SC once every other week in the Maintenance Phase (denoted as 
“360 mg QW/360 mg Q2W”)

Cohort E:  Subjects receiving CC-93538 360 mg SC once weekly in both the Induction 
Phase and the Maintenance Phase (denoted as “360 mg QW/360 mg QW”).
The OLE population will also consist of subjects who completed Period 2 of the Phase 1 open-
label drug-drug interaction study and met the eligibility criteria for Study CC-93538-EE-002.
Safety Analysis (Primary Endpoint): 
The assessment will include AEs, SAEs, AEs leading to discontinuation of study treatment, 
changes from baseline in laboratory values and vital signs, and incidence and type of laboratory, 
vital signs, and physical examination abnormalities.  All safety endpoints will be summarized by 
cohort (subjects from Study CC-93538-DDI-001 will be summarized separately) using descriptive 
statistics.  No statistical hypothesis testing will be performed on any safety results.
Overall safety and tolerability will be summarized for each drug presentation: the 360-mg dose of 
CC-93538 administered by 
 at a concentration of 
 mg/mL 
CC-93538, or by 
 at a concentration of 
 mg/mL CC-93538 administered
with the PFS device, or by 
 at a concentration of 
 mg/mL CC-93538
administered with the AI device utilizing descriptive statistics.
Efficacy Analysis (Exploratory Endpoints): 
Efficacy analyses will be descriptive for each of the Study CC-93538-EE-001 pre-defined cohorts
and will include the exploratory endpoints except for pharmacokinetic (PK) and biomarker 
endpoints.  The analyses of the PK endpoints and the immunogenicity secondary endpoint will be 
described separately in the PK Analysis Plan.  The biomarker endpoints and the related analyses 
will be described separately in the Biomarker Analysis Plan.  Subjects from Study CC-93538-
DDI-001 will be summarized separately.
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CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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For continuous endpoints (ie, mean change over time), descriptive statistics including number of 
subjects (n), mean, standard deviation (SD), median, minimum, and maximum will be provided 
by cohort at each time point.  In addition, the 95% confidence interval (CI) for the mean estimates 
will be presented for the following endpoints:  
 
 
 the mean change over time in the endoscopic features of EoE as measured by the EREFS 
from baseline, the mean change over time in the histologic features of EoE as measured by the 
EoE histology scoring system (EoEHSS) from baseline, and the mean change over time in mDSD 
composite score from baseline.
For categorical endpoints (ie, proportions), descriptive statistics including counts and percentages 
will be provided by cohort at each time point.  In addition, the 95% CI for the mean estimates will 
be presented for the following endpoints:  the proportion of subjects with histologic response 
defined as a peak esophageal eosinophil count ≤ 6/high-power field (hpf) and the proportion of 
subjects with histologic response defined as a peak esophageal eosinophil count < 15/hpf.
For subjects who enter the OLE study with clinical, histologic, or clinical and histologic response 
after completing the Maintenance Phase in Study CC-93538-EE-001, the durability of response 
will be reported as proportion of subjects who continue having their clinical, histologic, or clinical 
and histologic response at each time point, and will be reported by subjects’ original treatment in 
the Maintenance Phase.
External Data Monitoring Committee
An external, independent Data Monitoring Committee (DMC) will be convened and will be 
comprised of physician experts with experience in treating subjects with EoE, and 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 the duration of DMC implementation during the OLE 
study, will also be described in the DMC Charter.
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Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 2:...............................................7
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 2............................................7
PROTOCOL SUMMARY ........................................................................................................17
TABLE OF CONTENTS..........................................................................................................24
LIST OF TABLES....................................................................................................................28
LIST OF FIGURES ..................................................................................................................29
1
INTRODUCTION..................................................................................................30
1.1
Disease Background:  Eosinophilic Esophagitis......................................................30
1.2
Investigational Product:  CC-93538 ........................................................................32
1.2.1
Mechanism of Action ..............................................................................................32
1.2.2
Clinical Studies.......................................................................................................33
1.2.2.1
Phase 1 Study, M10-378.........................................................................................33
1.2.2.2
Phase 2 Study, CC-93538-AD-001..........................................................................34
1.2.2.3
Phase 1 Study, RPC02-1901 ...................................................................................34
1.2.2.4
Phase 1 Study, CC-93538-CP-001..........................................................................34
1.2.2.5
Phase 1 Study, CC-93538-CP-002..........................................................................35
1.2.2.6
Phase 1 Study, IM042-003......................................................................................36
1.2.2.7
Phase 2 Study, RPC02-201.....................................................................................36
1.3
Rationale ................................................................................................................38
1.3.1
Study Rationale and Purpose..................................................................................38
1.3.1.1
Benefit-Risk Assessment..........................................................................................39
1.3.2
Rationale for the Study Design................................................................................40
1.3.3
Rationale for Dose, Schedule and Regimen Selection..............................................40
1.3.4
Rationale for Pharmacodynamics and Potential Predictive Biomarkers..................42
2
STUDY OBJECTIVES AND ENDPOINTS...........................................................43
3
OVERALL STUDY DESIGN ................................................................................47
3.1
Phase 3 Program Design.........................................................................................47
3.2
Open-label Extension Study Design........................................................................48
3.2.1
Open-label Treatment Period..................................................................................49
3.2.2
End of Treatment and Safety Follow-up Visit..........................................................50
3.2.3
Worsening of EoE Symptoms or Lack of Improvement ............................................50
3.2.4
Planned Database Locks.........................................................................................51
3.3
Study Duration for Subjects....................................................................................51
3.4
End of Study...........................................................................................................52
4
STUDY POPULATION.........................................................................................52
4.1
Number of Subjects ................................................................................................52
4.2
Inclusion Criteria....................................................................................................52
4.3
Exclusion Criteria...................................................................................................54
5
TABLE OF EVENTS.............................................................................................57
6
PROCEDURES......................................................................................................64
6.1
Screening Period.....................................................................................................64
6.2
Open-label Extension Treatment Period..................................................................65
6.2.1
Additional Information Regarding Safety Laboratory Assessments .........................70
6.2.2
First Autoinjector Administration Visit ...................................................................70
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6.2.3
EoE Flare Assessment Visit ....................................................................................70
6.2.4
Early Termination or End of Treatment Visit ..........................................................71
6.3
Follow-up Period....................................................................................................72
6.3.1
Safety Follow-up Visits (Interim 8-week and Final 16-week)...................................72
6.4
Efficacy Assessment...............................................................................................72
6.4.1
Esophagogastroduodenoscopy (EGD) ....................................................................72
6.4.2
Clinical Symptoms of EoE.......................................................................................73
6.4.2.1
Modified Daily Symptom Diary (mDSD).................................................................73
6.4.2.2
Patient Global Impression of Severity (PGI-S)........................................................74
6.4.2.3
Clinician Global Impression of Severity (CGI-S) ....................................................74
6.4.2.4
Global Impression of Change in EoE Symptoms (GIC-EoE) ...................................75
6.4.2.5
Eosinophilic Esophagitis Symptom and Activity Index (EEsAI)...............................75
6.4.2.6
Pediatric Eosinophilic Esophagitis Symptom Severity Module (PEESS)..................75
6.4.2.7
Worsening of EoE Symptoms, EoE Flare, the EoE Flare Assessment Visit, 
and Lack of Improvement........................................................................................76
6.5
Anti-drug Antibody Assessments............................................................................76
6.6
Pharmacokinetics....................................................................................................77
6.6.1
Serum CC-93538 Assessments ................................................................................77
6.7
Biomarkers, Pharmacodynamics, Pharmacogenomics.............................................77
6.7.1
Circulating Biomarker Assessments........................................................................77
6.7.2
Tissue Biomarker Assessments................................................................................77
6.8
Additional and Optional Research...........................................................................78
6.8.1
Additional Research ...............................................................................................78
6.8.2
Optional Research..................................................................................................78
6.9
Subject-Reported Outcomes....................................................................................78
6.9.1
Health-related Quality of Life.................................................................................78
6.9.2
Autoinjector (AI) Administration Questionnaire/PFS Administration 
Questionnaire.........................................................................................................78
6.10
Health Resource Utilization....................................................................................79
6.11
Endolumenal Functional Lumen Imaging Probe (EndoFLIPTM) Sub-study..............79
7
DESCRIPTION OF STUDY TREATMENTS........................................................81
7.1
Description of Investigational Product(s)................................................................81
7.2
Treatment Administration and Schedule .................................................................81
7.2.1
Self-Administration.................................................................................................83
7.2.2
Missed Dose(s) .......................................................................................................83
7.2.3
Dose Adjustments ...................................................................................................84
84
7.2.5
Criteria for Discontinuation of Dosing ...................................................................85
7.2.6
Rescue Therapy ......................................................................................................85
7.3
Method of Treatment Assignment...........................................................................85
7.4
Packaging and Labeling..........................................................................................85
7.5
Investigational Product Accountability and Disposal ..............................................85
7.6
Investigational Product Compliance........................................................................86
8
CONCOMITANT MEDICATIONS AND PROCEDURES....................................87
8.1
Permitted Concomitant Medications and Procedures...............................................87
8.1.1
Rescue Therapy ......................................................................................................87
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8.2
Prohibited Concomitant Medications and Procedures..............................................87
8.3
Required Concomitant Medications and Procedures................................................88
9
STATISTICAL CONSIDERATIONS ....................................................................89
9.1
Overview................................................................................................................89
9.2
Study Population Definitions ..................................................................................89
9.3
Sample Size and Power Considerations...................................................................90
9.4
Background and Demographic Characteristics........................................................90
9.5
Subject Disposition.................................................................................................90
9.6
Efficacy Analysis....................................................................................................91
9.7
Safety Analysis.......................................................................................................91
9.8
Interim Analysis .....................................................................................................92
9.9
Other Topics...........................................................................................................92
9.9.1
Pharmacokinetics, Pharmacodynamics and Exposure-Response.............................92
9.9.2
Internal Safety Management Team..........................................................................92
9.9.3
External Data Monitoring Committee.....................................................................93
9.9.4
Steering Committee.................................................................................................93
10
ADVERSE EVENTS..............................................................................................94
10.1
Monitoring, Recording and Reporting of Adverse Events .......................................94
10.2
Evaluation of Adverse Events.................................................................................95
10.2.1
Seriousness.............................................................................................................95
10.2.2
Severity/Intensity ....................................................................................................96
10.2.3
Causality ................................................................................................................97
10.2.4
Duration.................................................................................................................97
10.2.5
Action Taken...........................................................................................................97
10.2.6
Outcome .................................................................................................................97
10.3
Abnormal Laboratory Values..................................................................................97
10.4
Pregnancy...............................................................................................................98
10.4.1
Females of Childbearing Potential .........................................................................98
10.5
Reporting of Serious Adverse Events......................................................................99
10.5.1
Safety Queries ........................................................................................................99
10.6
Adverse Events of Special Interest........................................................................100
10.7
Expedited Reporting of Adverse Events................................................................100
11
DISCONTINUATIONS .......................................................................................102
11.1
Treatment Discontinuation....................................................................................102
11.2
Study Discontinuation ..........................................................................................103
11.3
Emergency Contact...............................................................................................104
12
REGULATORY CONSIDERATIONS.................................................................105
12.1
Good Clinical Practice..........................................................................................105
12.2
Investigator Responsibilities .................................................................................105
12.3
Subject Information and Informed Consent...........................................................106
12.4
Confidentiality......................................................................................................106
12.5
Protocol Amendments...........................................................................................106
12.6
Institutional Review Board/Independent Ethics Committee Review and 
Approval ..............................................................................................................107
12.7
Ongoing Information for Institutional Review Board/ Ethics Committee ..............107
12.8
Termination of the Study ......................................................................................108
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13
DATA HANDLING AND RECORDKEEPING...................................................109
13.1
Data/Documents ...................................................................................................109
13.2
Data Management.................................................................................................109
13.3
Record Retention..................................................................................................109
14
QUALITY CONTROL AND QUALITY ASSURANCE......................................111
14.1
Study Monitoring and Source Data Verification....................................................111
14.2
Audits and Inspections..........................................................................................111
14.3
Investigational Medicinal Product Quality Issues..................................................111
15
PUBLICATIONS .................................................................................................113
16
REFERENCES.....................................................................................................114
17
APPENDICES......................................................................................................119
APPENDIX A
TABLE OF ABBREVIATIONS...........................................................119
APPENDIX B
MODIFIED DAILY SYMPTOM DIARY (MDSD) .............................123
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LIST OF TABLES
Table 1:
Study Objectives ....................................................................................43
Table 2:
Study Endpoints .....................................................................................44
Table 3:
Table of Events for the Open-label Extension Study...............................57
Table 4:
Abbreviations and Specialist Terms......................................................119
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CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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LIST OF FIGURES
Figure 1:
Overall Study Schema ............................................................................47
Figure 2:
Open-label Extension Study Schema ......................................................49
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1
INTRODUCTION
1.1
Disease Background: Eosinophilic Esophagitis
Eosinophilic esophagitis (EoE) is a chronic, debilitating, allergic/immune-mediated disease due to 
chronic esophageal inflammation with the development of dysphagia that affects food intake and 
quality of life.  The disease is characterized by symptoms related to esophageal dysfunction and 
by eosinophil-predominant inflammation of the esophageal mucosa.
While eosinophils are present in specific regions of the gastrointestinal (GI) tract, they are not 
normally found in the esophagus.  Patients with EoE demonstrate esophageal tissue infiltration of 
significant numbers of eosinophils and other pro-inflammatory cells, including mast cells and B 
and T lymphocytes (Mulder, 2011), the latter characterized by an enrichment of  CD4+ T 
regulatory and type 2 cytokine producing effector type 2 T helper (Th2) cells (Wen, 2019).  This 
infiltrating cellular profile along with over expression of cytokines, particularly interleukin-13 (IL-
13) and interleukin-5 (IL-5), strongly suggests that EoE is a type 2 cell-mediated inflammatory 
disease.  Many patients with EoE have other atopic diseases including asthma and food allergies, 
supporting the view that EoE likely represents a disease in which type 2 cells and eosinophils play 
key pathogenic roles (Straumann, 2012). 
Interleukin-13 is a pleotropic cytokine that has been shown to have a critical role in the 
immunopathogenesis of type 2 inflammation characteristic of EoE (Wechsler, 2014).  Pre-clinical 
and in vitro modeling have shown that IL-13 is overexpressed in the esophageal mucosa of EoE 
subjects and induces a gene transcript profile that overlaps with the EoE-specific esophageal 
transcriptome (Blanchard, 2007).  Interleukin-13 modulates cellular and molecular pathways 
involved in eosinophil recruitment (Brightling, 2010), esophageal barrier function (Sherrill, 2014), 
and tissue remodeling and fibrosis (Zuo, 2010).  Simulated altered expression of IL-13 and 
simulated blockade of IL-13 in animal models have also been shown to cause fluctuations in EoE 
disease status, esophageal function, and other related clinical consequences (Zuo, 2010; Kottyan, 
2014; Rothenberg, 2015a).
The extensive tissue remodeling, including epithelial thickening, and fibrosis that also 
characterizes EoE leads to esophageal stricture and narrowing.  Esophageal dysfunction, with 
symptoms of dysphagia (the most common symptom), chest pain and upper abdominal pain, and 
food bolus impaction is a direct consequence of these structural changes (Straumann, 2012).  
Natural history studies and molecular endotype analysis in adults demonstrate that EoE is a 
progressive fibrostenotic disease that, if not treated, usually leads to stricture formation (Shaheen, 
2018; Shoda, 2018).  The risk of stricture formation is proportional to the duration of untreated 
disease (Schoepfer, 2013; Dellon, 2014).  If left untreated, EoE transitions to a more fibrotic state 
that is associated with increased morbidity and further decreased quality of life.
In the United States (US), the prevalence of EoE increases with age and peaks in the age range of 
30 to 44 years (Dellon, 2018a).  An internal analysis conducted in March of 2019 using US 
commercial claims data demonstrated an increasing EoE prevalence rate over the last several years 
(MarketScan Database, 2018).  From 2011 to 2017, the prevalence for individuals aged 0 to 64 
years was 4.15 (95% confidence interval [CI]: 4.09 to 4.21) per 10,000 persons in 2011 and 10.73 
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(95% CI: 10.58 to10.88) per 10,000 persons in 2017.  Further, in 2017, adolescent patients, which 
will be included in the Phase 3 program, made up 10.7% of the total patients with EoE aged 12 to 
64 years. 
In the European Union (EU), the prevalence of EoE was reported to be between 1.4 in 10,000 
persons (Dellon, 2015), and 4.8 in 10,000 persons (Giriens, 2015). A pooled estimate from a meta-
analysis of population-based studies in North America, Europe, and Australia placed the 
prevalence of EoE somewhere in the middle of the range (2.27 per 10,000; 95% CI 1.34 to 3.60) 
(Arias, 2016).  Further, a rise in the incidence of EoE in multiple countries has been reported 
(Moawad, 2018).  Moreover, an additional meta-analysis of studies mainly conducted in North 
America (US and Canada) and Europe reported a pooled prevalence of 3.42 per 10,000 inhabitants 
with a 95% CI 2.31 to 4.75 (Navarro, 2019).
Although the definitive etiology of EoE is unknown, several factors that influence the risk of EoE 
have been identified.  Eosinophilic esophagitis is a disorder most likely triggered by food and/or 
aeroallergens (de Bortoli, 2017).  Disease pathogenesis involves activation of epithelial 
inflammatory pathways, impaired barrier function, increased production and/or activity of 
transforming growth factor-β, and induction of allergic inflammation by eosinophils and mast cells 
(Rothenberg, 2015b). 
The diagnosis of EoE is based on symptoms related to esophageal dysfunction, the presence of 
eosinophil-predominant inflammation on esophageal biopsy, characteristically consisting of a 
peak value of ≥15 eosinophils per high-power field (or approximately 60 eosinophils per mm2), 
and assessment of other causes that may be responsible for, or contributing to, symptoms and 
esophageal eosinophilia, particularly gastroesophageal reflux disease (GERD) (Dellon, 2018b).
The clinical manifestations commonly observed in adults with EoE include dysphagia, food 
impaction, chest pain that is often centrally located and may not respond to proton  pump inhibitors 
(PPIs), GERD-like symptoms/refractory heartburn, and upper abdominal pain (Kapel, 2008; 
Sgouros, 2006; Gonsalves, 2006; Shoda, 2018).  The clinical manifestations of EoE observed in 
adolescents include dysphagia and food impactions (Furuta, 2015).
The management of EoE includes pharmacologic, endoscopic, and dietary interventions, as 
outlined in a 2011 consensus statement (Liacouras, 2011) and guidelines provided by the United 
European Gastroenterology group (Lucendo, 2017).  Response to a trial of PPI therapy was 
previously used to rule out diagnosis of EoE.  However, recent studies have demonstrated that the 
demographics, endoscopic features, EoE biomarkers, and gene expression profiles do not reliably 
distinguish EoE from PPI-responsive esophageal eosinophilia.  Therefore, consensus 
recommendations have now advocated removal of a PPI trial for the purposes of establishing a 
diagnosis of EoE (Dellon, 2018b; Molina-Infante, 2016).  Proton pump inhibitors (PPIs) are 
instead viewed as a viable treatment alternative for EoE (through off-label use) with an overall 
clinical response and histologic response rate of 30% to 70% (Lucendo, 2017).  Given the ease of 
administration and long-term clinical experience, PPIs have been positioned as a first-line 
pharmacological option for most patients with EoE (Dellon, 2018b; Lucendo, 2017).  For patients 
without symptom and histologic improvement after PPI therapy, PPI therapy is discontinued.  The 
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current standard of care for both naïve and relapsing patients also included topical corticosteroids 
(swallowed or inhaled preparations) as first line treatment (as an add-on to PPIs or as stand-alone).  
Overall response rates are 60% to 80%.  However, the majority of patients relapse within 1 to 4 
months following discontinuation, requiring additional courses of therapy, and most patients lose 
response even if the steroids are continued long-term.  Nevertheless, steroids continue to be 
prescribed mostly off-label.  Although the dispersible tablet formulation of budesonide 
(JorvezaTM) was approved in the EU in early 2018 for the treatment of EoE in adults over 18 years 
of age, it is not currently approved in the US. The US Food and Drug Administration (FDA) has 
more recently approved dupilumab as a new treatment for EoE in adults and pediatric patients 12 
years and older, weighing at least 40 kg (US Food and Drug Administration, 2022). Dupilumab 
was also approved in the European Union (EU) to treat EoE in adults and adolescents 12 years and 
older, weighing at least 40 kg, who are inadequately controlled by, are intolerant to, or who are 
not candidates for conventional medicinal therapy in January 2023 (European Medicines Agency, 
2023).  Dupilumab is a monoclonal antibody against interleukin (IL)-4 receptor alpha that blocks 
IL-4 and IL-13 co-signaling through a shared receptor component, decreasing type 2 inflammation. 
Weekly treatment with dupilumab for 24 weeks in the pivotal study demonstrated histologic 
remission in approximately 60% of patients and improvements in symptomatic scores (Dellon, 
2022; Straumann, 2022). Dupilumab’s approval marks the introduction of use of biologics in the 
EoE treatment paradigm (Nhu, 2022).
Non-pharmacologic treatment strategies include dietary therapy and endoscopic dilations. Dietary 
therapy usually consists of an elemental formula, a 6-food elimination diet (SFED), or targeted 
elimination diet (Dellon, 2012).  Challenges to this approach include difficulty in compliance, 
effects on quality of life and social activities because patients have to avoid common foods such 
as milk and gluten (Straumann, 2018), and the frequent need for endoscopies to properly assess 
response to changes in food exposure.  Dilation of esophageal strictures has been reported to be 
effective for relieving dysphagia in adults and children with EoE (Lucendo, 2018), but it has no 
effect on underlying inflammation (Schoepfer, 2010; Robles-Medranda, 2010) and is not free of 
procedural complications (Schoepfer, 2014a).  Dilation is often reserved for patients who have 
failed other therapy. However, dilation may be required as initial therapy in EoE patients (often 
adults) who have high-grade strictures (Dellon, 2013; Furuta, 2007). 
Despite the recent advances in EoE treatment, significant unmet need still exists for a new and 
effective immunomodulatory treatment with an improved safety and tolerability profile, especially 
for long-term management.
1.2
Investigational Product: CC-93538
1.2.1
Mechanism of Action
CC-93538, also known as BMS-986355 (nonproprietary name, cendakimab), is a recombinant, 
humanized, high-affinity neutralizing (immunoglobulin G1 kappa [IgG1κ]) monoclonal antibody 
(mAb).  CC-93538 is highly selective for human IL-13 and was generated by humanization of a 
rodent anti-human IL-13 mAb, which was identified using hybridoma technology through 
immunization of mice with human Q110 variant recombinant IL-13.  
 
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 of CC-93538 is mutated at 
 
 to reduce effector function as suggested by literature reports (Hezareh, 2001; Lo, 2017). 
CC-93538 is produced by mammalian cell expression.
IL-13 is a cytokine that is expressed by a large number of cell types including most leukocytes, 
mast cells, epithelial cells, fibroblasts, and smooth muscle cells (Brightling, 2010).  CC-93538 has 
high affinity for wild-type IL-13 and a common variant of IL-13, Q110, which is associated with 
and enhances human allergic inflammation (Vladich, 2005).  
 
  This binding in turn prevents IL-13 
from binding to both IL-13 receptor alpha 1 (IL-13Rα1) and IL-13 receptor alpha 2 (IL-13Rα2) 
(Ying, 2010), where IL-13Rα1 and IL-13Rα2 may be implicated in inflammation and in the 
progression of tissue remodeling or fibrosis in EoE, respectively (Doran, 2017; Hershey, 2003; 
Fichtner-Feigl, 2006; Fichtner-Feigl, 2008).  
1.2.2
Clinical Studies
CC-93538 has been investigated in a Phase 1 clinical study in healthy adults and adults with 
mild-to-moderate controlled asthma, Study M10-378; a Phase 2 clinical study in adults with 
moderate-to-severe atopic dermatitis, Study CC-93538-AD-001; and a Phase 2 clinical study in 
adults with EoE, Study RPC02-201.  Additional Phase 1 single-dose pharmacokinetic (PK) studies 
in adult healthy volunteers, RPC02-1901, CC-93538-CP-001, and CC-93538-CP-002 were also
completed, and preliminary results are available for a fourth PK study, IM042-003 Part 1.
1.2.2.1
Phase 1 Study, M10-378
The PK of CC-93538 was examined in healthy adults (between 18 and 55 years of age, inclusive) 
and adults with mild-to-moderate asthma in Study M10-378.  The PK data included results from 
16 healthy subjects after intravenous (IV) infusion over the 0.3 mg/kg to 10.0 mg/kg CC-93538 
dose range, 12 subjects with mild-to-moderate asthma after IV infusion over the 0.3 mg/kg to 10.0 
mg/kg dose range, and 8 subjects with mild-to-moderate asthma after subcutaneous (SC)
administration of 0.3 or 3.0 mg/kg for 3 weekly doses.  After IV administration, the exposures, as 
determined by CC-93538 area under the curve (AUC) and observed maximum serum
concentration (Cmax), increased in a dose-dependent manner and were similar in healthy subjects 
and subjects with asthma.  The median time to the observed maximum concentration (tmax) for CC-
93538 following SC administration in subjects with asthma was approximately 108 hours or 4.5 
days.  The mean estimated volume of distribution at steady state for CC-93538 ranged from 69.7 
to 97.7 mL/kg, and the mean systemic clearance for CC-93538 ranged from 0.106 to 0.154 
mL/hr/kg.  The mean terminal elimination half-life (t½) for CC-93538 ranged from 16.4 to 26.7 
days.  See Section 1.2.2.7 for PK results from Phase 2 Study RPC02-201. 
In Study M10-378, CC-93538 was well tolerated and had an acceptable safety profile when 
administered as a single dose up to 10.0 mg/kg IV or as 3 weekly doses of 0.3 and 3.0 mg/kg SC.  
There were no deaths.  One serious adverse event (SAE) of bunionectomy which was considered 
unrelated to study drug was reported in a healthy subject.  The adverse event (AE) profile in healthy 
adults was similar to that observed in subjects with asthma.  No dose-related increases or 
administration-specific trends in treatment-emergent AEs (TEAEs) were observed.  No subjects 
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discontinued study treatment due to a TEAE.  No infusion-related reactions were reported.  Anti-
drug antibodies (ADAs) were detected in approximately 28% (10 of 36 subjects) of subjects 
receiving CC-93538 but were usually transient and did not interfere with CC-93538 PK.
1.2.2.2
Phase 2 Study, CC-93538-AD-001
Study CC-93538-AD-001 is an ongoing, 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 atopic dermatitis. A total of 220 subjects were randomized in the 
study, and the clinical study conduct is complete. The study results were still being analyzed, and
the clinical study report (CSR) was not yet final at the time of protocol finalization.
1.2.2.3
Phase 1 Study, RPC02-1901
Study RPC02-1901 was a Phase 1, randomized, open-label, single-dose parallel-group study to 
characterize the PK of CC-93538 in healthy adult subjects following a single 360 mg IV infusion 
or 360 mg SC administration using the 150 mg/mL formulation.  Twenty-four healthy adult 
subjects were randomized to receive a single CC-93538 360 mg dose either via IV infusion (N =
12) or SC injection (N = 12).  Following SC administration, the absorption of CC-93538 was slow 
with a median tmax of approximately 
 hours (approximately  days).  CC-93538 showed a long 
elimination t½ of approximately 
 to 
 hours (approximately 
 to 
 days) and a small 
volume of distribution of approximately L.  The SC bioavailability of CC-93538 was estimated 
to be approximately 
.  Anti-CC-93538 antibodies were detected in 
 of 24 subjects. Of those 
 subjects,  had pre-existing antibodies and there was no indication that the response increased 
after treatment.  Thus, in  out of 24 (
) subjects, treatment-induced ADAs were detected.  Of 
those 
subjects for which treatment-induced ADAs were detected, the ADA titers were low for 
of them.  However,  subject had titers that were higher than the others (
).  Despite 
this, there was no indication that exposure was impacted in that subject or in any of the subjects 
who had treatment-induced antibodies.  None of the subjects who had treatment-induced ADAs
had TEAEs suspected by the Investigator to be related to CC-93538.  
There were no deaths, SAEs, AEs leading to discontinuation, or infusion/injection site or 
hypersensitivity reactions.  The most frequently reported (2 or more subjects) TEAEs were 
.  A single 360 mg IV infusion or SC administration of CC-93538 (for 
each route of administration) was well tolerated and had an acceptable safety profile in healthy 
adult subjects in Study RPC02-1901.
1.2.2.4
Phase 1 Study, CC-93538-CP-001
Study CC-93538-CP-001 was a Phase 1, randomized, open-label, single-dose study to evaluate the 
PK of CC-93538 in healthy Japanese and Caucasian adult subjects.  Forty-eight subjects (24 
Japanese and 24 Caucasians) received either a single 180 mg or 360 mg SC dose of CC-93538.  
Following SC administration of either 180 mg or 360 mg, the absorption of CC-93538 was slow 
with a median tmax of 5.4 to 7.5 days.  A long elimination t½ of approximately 18.7 to 23.4 days 
and a small volume of distribution of approximately 7.4 to 9.8 L were observed.  The 90% CI for 
the least squares geometric mean ratios for Cmax and AUC from a combined dose analysis were 
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found to be approximately within the typical 80% to 125% bound.  These data suggest that the PK 
of CC-93538 is similar between Japanese and Caucasian subjects.
Anti-drug antibodies were detected in 20 of 48 subjects.  Of the 20 subjects (41.7%) with positive 
anti-CC-93538 antibody response, 12 TEAEs were reported; 1 of which (injection site pain) was 
considered by the Investigator to be related to study drug.  There was no indication that CC-93538 
exposure was impacted in any of the subjects with positive ADAs, and ADA response did not 
impact the safety of CC-93538 following a single 180 mg or 360 mg SC dose.  There were no 
deaths, SAEs, or TEAEs leading to study discontinuation.  All TEAEs were mild to moderate in 
severity.  The only TEAEs reported in 2 or more subjects included
 
. Overall, CC-93538 was well tolerated and had an 
acceptable safety profile in healthy Japanese and Caucasian adult subjects following a single SC 
dose of 180 mg or 360 mg.
1.2.2.5
Phase 1 Study, CC-93538-CP-002
Study CC-93538-CP-002 was an open-label, randomized, parallel design study to evaluate the PK 
comparability, safety, tolerability, and immunogenicity of a single SC dose of 360 mg CC-93538
using 2 different drug concentrations, 180 mg/mL and 150 mg/mL, in healthy adult subjects. A 
total of 52 subjects were enrolled and randomized 1:1 to receive a single 360 mg SC dose of CC-
93538 using either 180 mg/mL (one injection of 2.0 mL) or 150 mg/mL (two injections of 1.2 mL 
each) drug concentrations.
During the CC-93538-CP-002 study, following SC administration of either the 150 mg/mL or 180 
mg/mL concentrations, the statistical comparison of PK parameters for CC-93538-CP-002 showed 
that the point estimate for the ratios of geometric least squares means of peak and total exposure 
parameters for the comparison of 180 mg/mL versus 150 mg/mL treatments were close to 1 and 
their 90% CI were contained entirely within 80% to 125%, indicating the two formulations were 
bio-comparable. The nonparametric analysis of serum CC-93538 tmax using Hodges-Lehmann 
showed the median difference between these treatments was not statistically significant.
The two concentrations of CC-93538, 150 mg/mL or 180 mg/mL, administered as a single dose of 
360 mg, were both safe and well tolerated in healthy adults. The two concentrations had similar 
PK profiles and were biocomparable. No differences were observed in safety, tolerability, or 
immunogenicity. Anti-drug antibodies developed on Day 56 or later in 8 subjects total (5 subjects 
receiving 150 mg/mL and 3 subjects receiving 180 mg/mL).
The ADA profiles were similar 
between subjects receiving 150 mg/mL and 180 mg/mL. There was no indication that the ADA 
response impacted the safety, tolerability, and PK of CC-93538 following a single SC dose of 
360 mg using either 150 mg/mL or 180 mg/mL. ADAs were not associated with differences in 
safety, tolerability, or PK.
Overall, 17 of 52 subjects (32.7%) reported at least one TEAE.  The majority of TEAEs were mild 
to moderate in severity. The most frequent TEAEs reported included injection site bruising (2
subjects from each treatment group) and coronavirus disease 2019 (COVID-19). No other TEAEs 
were reported in more than one patient. Overall, only 2 subjects reported at least one TEAE related 
to study drug (frequent bowel movements [one subject from the 150 mg/mL treatment group] and 
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injection site pain [one subject from the 180 mg/mL treatment group]). No deaths or SAEs were 
reported, and no subject had a TEAE that led to early discontinuation from the study. All TEAEs 
were recovered/resolved by the end of the study.
1.2.2.6
Phase 1 Study, IM042-003
Study IM042-003 was an open-label, randomized, 2-part parallel design study to compare the PK 
of single subcutaneous injections of CC-93538 administered with an AI versus PFS, and to 
evaluate the PK of CC-93538 when administered by the AI at different injection sites, in healthy 
subjects. A total of 104 subjects were enrolled. In Part 1 of the study, 64 subjects were randomized 
1:1 to receive CC-93538 360 mg SC either by PFS or by AI in the abdomen. In Part 2 of the study, 
40 subjects were randomized 1:1 to receive CC-93538 360 mg SC by AI in either the upper arm 
or the upper thigh area. Part 2 began enrollment after the completion of Part 1; the results of which 
will be included in the final CSR. 
In Part 1 of the study, following SC administration of CC-93538 360 mg, either by PFS or AI, the 
preliminary statistical comparison of PK parameters showed that the 90% confidence interval (CI) 
for the ratios of geometric least squares means of peak and exposure parameters for the comparison 
of PFS vs AI were contained entirely within 80% to 125%, indicating the 2 devices (PFS and AI) 
are biocomparable.
Overall, 27 of 64 subjects (42.2%) reported at least 1 TEAE. There were 14 subjects (43.8%) who 
reported 29 TEAEs after receiving CC-93538 with the PFS and 13 subjects (40.6%) reported 18 
TEAEs after receiving CC-93538 with the AI. The most frequently reported TEAEs were 
arthropod bite (7 subjects), increased alanine aminotransferase (ALT) (5 [7.8%] subjects), and 
headache (4 [6.3%] subjects). Other TEAEs reported in more than one subject included injection 
site erythema, muscle strain, blood creatine phosphokinase (CPK) increased, and constipation. 
Except for 1 event of moderate TEAE (CPK elevation) which was determined not to be related to 
study drug by the Investigator, all TEAEs were mild in severity and were recovered/resolved at 
the end of the study. No deaths or SAEs were reported, and no subject had a TEAE that led to 
early discontinuation from the study. The safety profile of CC-93538 was comparable between 
subjects receiving a single dose of 360 mg/2 mL by PFS or AI.
Anti-drug antibodies (ADAs) were detected in 10 subjects (4 in the PFS arm and 6 in the AI arm
[1 subject in the AI arm had existing ADAs at baseline]). ADA profiles were similar between 
subjects receiving CC-93538 with the PFS or AI. There was no indication that the ADA response 
impacted the safety, tolerability, or PK of CC-93538 following a single SC dose of 360 mg with 
the PFS or AI.
The two presentations of CC-93538, given by PFS or AI, administered as a single dose of 360 mg, 
were well tolerated and had an acceptable safety profile in healthy adults. No differences were 
observed in safety, tolerability, or immunogenicity.
1.2.2.7
Phase 2 Study, RPC02-201
Study RPC02-201 was a Phase 2, multicenter, multinational, randomized, double-blind, placebo-
controlled parallel-group clinical study to evaluate the efficacy and safety of CC-93538 in adult 
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subjects with EoE (Hirano, 2019).  Subjects were stratified 1:1 by previously defined steroid 
refractory status, as determined by the Investigator (47% of enrolled subjects were steroid 
refractory).  After a Screening Period to determine eligibility, adult subjects with EoE were 
randomly assigned in a 1:1:1 ratio 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.  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 (86%) entered the OLE and 66 
(66.7%) subjects completed Week 52 of the OLE.
In Study RPC02-201, the primary endpoint (changes in esophageal eosinophil count) was met. The 
mean changes from baseline to Week 16 in mean esophageal eosinophil count measured in the 5 
most inflamed high-power fields (hpfs) from the esophageal biopsies in the placebo, CC-93538 
180 mg, and CC-93538 360 mg groups were -4.42, -94.76, and -99.90, respectively.  The 
difference in mean change from baseline to Week 16 between each CC-93538 group and the 
placebo group was statistically significant (p < 0.0001) for each comparison.  Ad hoc analysis 
showed statistically significant differences between both dose groups and placebo in the 
subgroups, subjects known to be steroid-refractory and subjects not known to be steroid-refractory.  
CC-93538 significantly reduced peak esophageal eosinophil count and increased the number of 
subjects with < 15 eosinophils/hpf.  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.  Improvements in dysphagia symptoms based on mean change 
from baseline to Week 16 in the Dysphagia Symptom Diary (DSD) composite score, as assessed 
by the DSD instrument over the prior 2 weeks were also observed (although not statistically 
significant; the study was not powered for this endpoint) with the 360 mg dose (-6.41 in the placebo 
group compared to -13.31 in the CC-93536 360 mg group).  Ad hoc analysis revealed a numerically 
greater decrease in DSD composite score was observed in the CC-93538 360 mg group compared 
with the placebo group for the subgroup of subjects known to be steroid-refractory; however, the 
difference trended toward but did not reach statistical significance (p = 0.0547).  An ad hoc analysis 
of the change from baseline to different time points in the DSD composite score demonstrated 
statistically significant differences between CC-93538 360 mg and placebo at Week 8 (p = 0.0197) 
and Week 12 (p = 0.0460) in subjects known to be steroid refractory.
For subjects that received active treatment in the DB Treatment Period, long-term treatment (52 
weeks) with CC-93538 360 mg in the OLE showed sustained improvements in esophageal 
eosinophil count and other inflammatory features of EoE.  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.  
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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%, 
12.9%, and 26.5% of subjects in the placebo, CC-93538 180 mg, and CC-93538 360 mg groups, 
respectively.  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.  No deaths were 
reported.  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).  Anti-drug antibodies were 
assessed and were not associated with any safety findings.  
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.  CC-93538 trough concentration 
data showed steady state was reached between Weeks 12 and 16 of dosing, consistent with the t½.
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.
Refer to the Investigator’s Brochure (IB) for detailed information concerning the available 
pharmacology, toxicology, drug metabolism, clinical studies, and adverse event profile of the 
investigational product (IP).
1.3
Rationale
1.3.1
Study Rationale and Purpose
There is strong preclinical evidence for the role of IL-13 in the underlying pathophysiology of 
EoE. Results of the CC-93538 Phase 2 EoE study indicate that targeting IL-13 with CC-93538 
significantly improved many of the important disease features of EoE and was well tolerated.  In 
this study (RPC02-201) of 99 adult subjects with EoE, weekly administration of CC-93538 360 mg 
SC reduced mean esophageal eosinophil count and improved other inflammatory and symptomatic 
parameters.  The Phase 2 data results therefore support the continued development of CC-93538 
as a novel treatment for EoE.  The single pivotal Phase 3 Study, CC-93538-EE-001, is designed to 
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Final: 30 Jun 2023
39
confirm and extend the findings obtained from the positive Phase 2 study with CC-93538, and the 
OLE Study, CC-93538-EE-002, will continue to investigate the long-term safety profile and 
durability of response of CC-93538 in adult and adolescent subjects with EoE.
Study CC-93538-DDI-001 is a Phase 1, open-label, single-sequence study designed to evaluate 
potential disease-mediated drug-drug interaction with selected cytochrome P450 substrates and to 
evaluate the safety of CC-93538 with or without CYP substrates in adult subjects with active 
eosinophilic esophagitis receiving CC-93538.  Subjects participating in the parent Study CC-
93538-DDI-001 will be offered the opportunity to transition to OLE Study CC-93538-EE-002,
allowing for continued access to CC-93538.
1.3.1.1
Benefit-Risk Assessment
As few treatment options exist for patients with EoE, there is an unmet need for new 
pharmacotherapies targeting the pathophysiology of EoE with a safety and tolerability profile 
acceptable for long-term treatment.  Based on the clinical safety and efficacy data with CC-93538 
reported to date, including results from the completed Phase 2 EoE study, the benefit-risk 
assessment of CC-93538 supports further development in EoE and other inflammatory conditions.  
The overall safety profile of CC-93538 remained consistent with the information that has been 
presented in the IB. Please refer to the IB for additional information.
While CC-93538 is a biologic immunomodulator targeting IL-13, it was well tolerated in the Phase 
2 study conducted in EoE subjects, without an increased risk of serious infection.  Other 
immunomodulatory biologics in development or marketed for type 2 inflammatory diseases with 
a related mechanism of action, for example, dupilumab (targeting the interleukin-4 [IL-4] 
receptor), lebrikizumab (targeting IL-13), and tralokinumab (targeting IL-13) also have not been 
associated with an increased risk of serious viral infections.  Although targeted coronavirus disease 
2019 (COVID-19) related research with these agents is limited, small studies conducted in patients 
with atopic dermatitis from high endemic areas (eg, Lombardy, Italy) provides supplemental, real-
world evidence that there does not appear to be an increased risk for COVID‐19 infection in 
patients treated with dupilumab (Carugno, 2020), which has a mechanism of action similar to CC-
93538.
In order to minimize the overall risk to subjects, this protocol has inclusion and exclusion criteria 
appropriate to the population and proposed treatments (see Section 4.2 and Section 4.3). 
Exclusionary screening tests will be used to identify latent tuberculosis (TB), viral hepatitis, human 
immunodeficiency virus (HIV), and other risk assessment, such as a detailed assessment of 
medical history, will be performed. Each study visit will include an assessment for AEs, and 
subjects who develop an intercurrent illness between study visits are encouraged to contact the 
Investigator, who will determine if a clinical assessment is required. The Sponsor has also 
developed guidance for Investigators on how to manage a subject with a clinical suspicion of, or a 
diagnosis of, COVID-19. This includes criteria for 
 permanently 
discontinuing IP (
and Section 7.2.5), and 
 
. In order to facilitate reporting of COVID-19 events that 
occur during the study, all AEs and SAEs related to severe acute respiratory syndrome coronavirus 
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2 (SARS-CoV-2) or COVID-19 must be reported from the time of consent (Section 10.1). In 
addition, such AEs or SAEs will also trigger additional data collection through supplementary
safety report forms, which will allow the Sponsor to further evaluate these events.
While the global COVID-19 pandemic has been identified as a potential risk to clinical trial 
subjects in general, and it may particularly affect individuals with underlying chronic diseases, the 
overall benefit-risk for participation in this EoE study with CC-93538 is considered favorable.  The 
individual benefit-risk considerations regarding COVID-19 infection remains the responsibility of 
the Investigator.  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.
Non-live COVID-19 vaccination is allowed and will be documented as a 
concomitant medication within the study.  The efficacy and safety of non-live vaccines (including 
non-live COVID-19 vaccines) in subjects receiving CC-93538 are unknown.
1.3.2
Rationale for the Study Design
The Phase 3 program includes a multicenter, multinational, randomized, double-blind, placebo-
controlled induction and maintenance study to evaluate the efficacy and safety of CC-93538 in 
adult and adolescent subjects with EoE (Study CC-93538-EE-001, the core Phase 3 study) with a 
separate, optional Open-label Extension study (OLE; Study CC-93538-EE-002).  
The current OLE Study CC-93538-EE-002 is an open-label, uncontrolled study design to evaluate 
the longer-term safety profile as well as durability of response of administration of a 
 
level of CC-93538. The study will enroll subjects who participated in and complete the Induction 
and Maintenance Study, CC-93538-EE-001, as well as subjects who do not qualify for entry into 
the Maintenance Phase of the study.  Subjects who experience a severe EoE flare requiring 
endoscopic intervention and/or rescue therapy during the Induction or Maintenance Phase and 
complete the Induction or Maintenance Phase, respectively will also have the opportunity to 
participate. In addition, subjects participating in the parent Study CC-93538-DDI-001 who 
complete assessments in Period 2 through the End of Treatment Visit (Week 18) and who meet all 
eligible criteria will be offered the opportunity to transition to the OLE Study CC-93538-EE-002.  
See Section 3.2 for details.  Rationale for the CC-93538 dose selection is discussed in 
Section 1.3.3.
An advisory panel of patients with EoE and their caregivers has been consulted and input has been 
sought on the protocol design and development of patient-facing materials and recruitment 
initiatives. A series of 3 advisory boards took place between March 2021 and March 2022. The 
feedback and insights from these members of the EoE community have been considered in the trial 
awareness and recruitment materials developed for the study. The Sponsor has ongoing 
partnerships with US-based and global patient advocacy groups to deliver trial awareness 
initiatives for the study.
1.3.3
Rationale for Dose, Schedule and Regimen Selection
Based on results from the Phase 2 Study RPC02-201, the CC-93538 360 mg SC once weekly dose 
was selected for Phase 3.  In addition, this study is designed to test if induction of response at the 
360 mg SC once weekly dose level followed by continued treatment at a lower dose level through 
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Final: 30 Jun 2023
41
administration of a less frequent dosing regimen would provide a similar persistence of response.  
PK modeling demonstrated the average exposure for the 
 mg dose once weekly and the 
 
mg dose once every other week is very similar.  The fluctuation between Cmax and Ctrough is larger 
in the 
 mg dose administered every other week compared to the 
 mg dose administered 
every week but this is not expected to result in any clinically relevant differences between the 2
regimens. Further, a dose higher than 
 mg SC once weekly is not expected to provide additional 
therapeutic benefit, as trough concentrations observed in the 
 mg SC once weekly dose during 
the DB Treatment Period in the Phase 2 study exceeded the estimated in vitro EC95 (95% of the 
maximal effective concentration) for IL-13 neutralization.  Data from Study RPC02-201 also 
provide support that the intravenous (IV) loading dose (10 mg/kg) is not required to achieve 
optimal efficacy.  Subjects in the placebo group from the DB Treatment Period who transitioned 
to the CC-93538 
 mg SC regimen without receiving the IV loading dose in the OLE showed 
improvement in dysphagia symptoms and comparable reduction in eosinophil count at Week 12 
of the OLE as was observed at Week 16 of the DB Treatment Period for subjects treated with 
CC-93538 
 mg with the IV loading dose. These subjects also showed a mean Ctrough
concentration (56.8 μg/mL) approximately 5-fold higher than the half maximal effective 
concentration (EC50; 10 μg/mL) at Week 2 of the OLE. Collectively, PK and efficacy data support 
the IV loading dose is not needed to achieve optimal efficacy. 
Therefore, because (1) the CC-93538 360 mg once weekly regimen has shown an effect on both 
histological and clinical endpoints in Study RPC02-201, (2) the CC-93538 
 mg once weekly 
regimen has shown a relevant histological but not clinical effect in the same study, and (3) the CC-
93538 
mg once every other week regimen is not expected to achieve average concentrations 
different than the 
 mg once weekly regimen, the 
 mg once weekly dose was selected for the 
Induction Phase and the 
 mg once weekly and 
 mg once every other week doses were 
selected for the Maintenance Phase in Study CC-93538-EE-001.  Furthermore, population PK 
analysis indicated that age is not a significant covariate for CC-93538 PK parameters suggesting 
adolescents with a body weight of at least 40 kg will display similar CC-93538 exposures to adults.
For the OLE Study, CC-93538-EE-002, all subjects will receive CC-93538 360 mg SC once 
weekly. The dosing regimen for the OLE (ie, a change to an every other week dosing regimen) 
may be revised after results from the Induction and Maintenance Study, CC-93538-EE-001, are 
available and the optimal dosing regimen is confirmed. A PFS presentation of 
 
administered as a 
instead of 
 of 
 each for 
the full dose of 360 mg was introduced in Protocol Amendment 1. In Protocol Amendment 2, the 
CC-93538 360 mg SC dose will be administered by a 
 provided in a
 AI. The Study CC-93538-CP-002 results demonstrated that a 
 of
 mg 
CC-93538, when administered as either a 
 at a concentration of 
 mg/mL or 
 
 at a higher concentration of
 mg/mL, were both safe and well tolerated in healthy 
adults. The two formulations had similar PK profiles and were biocomparable. No differences 
were observed in safety, tolerability, or immunogenicity. The ADA profiles were similar between 
subjects receiving
 mg/mL and 
 mg/mL. There was no indication that the ADA response 
impacted the safety and PK of CC-93538 following 
 SC dose of 
 mg using either 
 
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CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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mg/mL or 
 mg/mL.  ADAs were not associated with differences in safety, tolerability, or PK.
Overall, the results of Study CC-93538-CP-002 support the introduction of the 
 
PFS presentation administered as a 
in Protocol Amendment 1. Further, Study 
IM042-003 Part 1 preliminary results demonstrated that the 
 
. The two presentations of CC-93538, given by PFS or AI, administered as a 
 dose of 
 mg, were well tolerated and had an acceptable safety profile in healthy adults.  
 
  The results of Study IM042-003 support the 
introduction of the 
 AI presentation in Protocol Amendment 2. 
1.3.4
Rationale for Pharmacodynamics and Potential Predictive Biomarkers
EoE is characterized by eosinophil-predominant inflammation and additional pathogenesis 
including esophageal tissue remodeling and over-expression of cytokines.  Biomarkers that are 
thought to play a role in EoE disease pathogenesis, such as circulating periostin, eotaxin-3, and 
IL-13, and markers of epithelial mesenchymal transition (EMT), eotaxin-3, and periostin in 
esophageal biopsy tissue as well as Endolumenal Functional Lumen Imaging Probe (EndoFLIP™)
assessment will be evaluated for potential diagnostic or prognostic importance.
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2
STUDY OBJECTIVES AND ENDPOINTS
Table 1:
Study Objectives
Primary Objective
The primary objective of the study is:

To evaluate the long-term safety and tolerability of CC-93538 in subjects with eosinophilic 
esophagitis (EoE)
Secondary Objective
The secondary objective is:

To characterize the immunogenicity profile of CC-93538 following long-term treatment
Exploratory Objectives
The exploratory objectives are:

To estimate the long-term efficacy of CC-93538 in reducing dysphagia symptoms and
esophageal eosinophil counts

To estimate the long-term efficacy of CC-93538 in improving the endoscopic and histologic 
features of EoE

To assess trough concentrations of CC-93538 in subjects with EoE

To conduct a population pharmacokinetic (PK) analysis to characterize the population PK of 
CC-93538 and to evaluate the exposure-response or pharmacodynamic relationships between 
dose (or concentration) and efficacy, safety, and biomarkers

To estimate improvements in subject and clinician rating of disease severity and subject 
impression of change in EoE symptoms

To estimate improvements in patient-reported outcome measures of EoE symptoms

To estimate improvements in additional EoE symptoms reported by subjects

To estimate health-related quality of life and work productivity

To estimate the frequency of successful self-administration of CC-93538 by PFS under 
supervised (in-clinic) and unsupervised (at home) conditions

To estimate the frequency of successful self-administration of CC-93538 by AI under 
supervised (in-clinic) and unsupervised (at home) conditions

To estimate the utilization of health care resources 

To explore the clinical profile of CC-93538 as a function of EoE biomarker expression

To explore the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 
serologic status on subjects receiving CC-93538, on EoE, and to support health authority 
requests

To estimate improvements in esophageal distensibility in subjects participating in the 
EndoFLIP sub-study, if applicable
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Protocol CC-93538-EE-002
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Final: 30 Jun 2023
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Table 2:
Study Endpoints
For OLE study endpoints, OLE baseline will be used.  In the Statistical Analysis Plan, baseline 
comparisons will be defined and additional subgroup analyses will be described.
Endpoint
Name
Description
Timeframe
Primary
Safety and 
Tolerability
Safety and tolerability of long-term treatment with CC-
93538 evaluated by the incidence, severity, and 
relationship to CC-93538 of adverse events (AEs), serious 
adverse events (SAEs), clinical laboratory abnormalities, 
changes in vital signs, and physical examination 
abnormalities 
Baseline through 
Safety Follow-up 
Visit
Secondary 
Immuno-
genicity
Immunogenicity of CC-93538 assessed through the 
incidence of anti-drug antibodies, including neutralizing 
antibodies when warranted
Baseline through 
Safety Follow-up 
Visit
Exploratory
Change in DD 
Clinical 
Response
 
 
Baseline through 
OLE Week 24, 
Week 48, and 
Week 104
Eosinophil 
Histologic 
Response (≤ 
6/hpf)
The proportion of subjects with eosinophilic histologic 
response defined as a peak esophageal eosinophil count ≤ 
6/high-power field (hpf)  
OLE Weeks 24, 
48, and 104
Durability of
Histologic 
Response 
(≤6/hpf)
The proportion of subjects previously treated with CC-
93538 in CC-93538-EE-001 and with peak esophageal 
eosinophil count ≤ 6/hpf at OLE baseline who continue to 
have a peak esophageal eosinophil count ≤ 6/hpf
OLE Weeks 24, 
48, and 104
Eosinophil 
Histologic 
Response 
(<15/hpf)
The proportion of subjects with eosinophilic histologic 
response defined as a peak esophageal eosinophil count < 
15/hpf 
OLE Weeks 24, 
48, and 104
EREFS
The mean change over time in the endoscopic features of 
eosinophilic esophagitis (EoE) as measured by the EoE 
Endoscopic Reference Score (EREFS) from baseline 
OLE Weeks 24, 48 
and 104
EoEHSS
The mean change over time in the histologic features of 
EoE as measured by the EoE histology scoring system 
(EoEHSS) from baseline  
OLE Weeks 24, 
48, and 104
DD Clinical 
Responder 
Definition
The proportion of subjects with a ≥ 50% decrease in 
dysphagia days (DD) from baseline  
Baseline through 
OLE Week 24, 
Week 48, and 
Week 104
Clinical and 
Histologic 
Response 
Composite
The proportion of subjects with histologic response 
defined as a peak esophageal eosinophil count < 15/hpf 
and dysphagia symptom response defined as the 
proportion of subjects with ≥ 50% decrease in dysphagia 
days (DD) from baseline 
OLE Weeks 24, 
48, and 104
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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Table 2:
Study Endpoints
For OLE study endpoints, OLE baseline will be used.  In the Statistical Analysis Plan, baseline 
comparisons will be defined and additional subgroup analyses will be described.
Endpoint
Name
Description
Timeframe
Clinical and 
Histologic 
Response 
Composite
The proportion of subjects with histologic response 
defined as a peak esophageal eosinophil count ≤ 6/hpf 
and dysphagia symptom response defined as the 
proportion of subjects with ≥ 50% decrease in dysphagia 
days (DD) from baseline
OLE Weeks 24,
48, and 104
Durability of 
Response 
For subjects entering the OLE with clinical, histologic, or 
clinical and histologic response after completing the 
Maintenance Phase in Study CC-93538-EE-001, the 
proportion of subjects with response (clinical, histologic, 
or clinical and histologic) 
Baseline through 
OLE Week 24, at 
Week 48, and 
Week 104 for
clinical; Weeks 24,
48, and 104 for 
histologic
mDSD 
Composite 
Score
The mean change over time in modified Daily Symptom 
Diary (mDSD) composite score from baseline 
Baseline through 
OLE Week 24, 
Week 48, and 
Week 104
Pharmaco-
kinetics
Measurements of trough concentrations of CC-93538 in 
subjects with EoE
Through OLE 
Treatment Period
Population 
Pharmaco-
kinetics
CC-93538 population pharmacokinetic parameters and 
covariates
Through Safety 
Follow-up Visit
Exposure-
response, 
Pharmaco-
dynamic 
Relationship  
Exposure-response or pharmacodynamic relationships 
between dose (or concentration) and efficacy, safety, and 
biomarkers 
Through Safety 
Follow-up Visit
PGI-S
The proportion of subjects demonstrating improvements 
in Patient Global Impression of Severity (PGI-S) rating of 
EoE symptoms from baseline 
OLE Weeks 24, 
48, and beyond
CGI-S
The proportion of subjects demonstrating improvements 
in Clinician Global Impression of Severity (CGI-S) rating 
of EoE symptoms from baseline
OLE Weeks 24, 
48, and beyond
GIC-EoE
The proportion of subjects demonstrating improvements 
in Global Impression of Change in EoE symptoms (GIC-
EoE) from baseline
OLE Weeks 24 
and 48
EEsAI
The mean change in dysphagia clinical symptom 
frequency and severity as assessed by the Eosinophilic 
Esophagitis Activity Index (EEsAI) total score from 
baseline and proportion of subjects that meet various 
response thresholds (including but not limited to EEsAI 
score ≤ 20)
OLE Weeks 24, 
48, and beyond
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Table 2:
Study Endpoints
For OLE study endpoints, OLE baseline will be used.  In the Statistical Analysis Plan, baseline 
comparisons will be defined and additional subgroup analyses will be described.
Endpoint
Name
Description
Timeframe
PEESS
The mean change in adolescent subjects’ EoE symptoms 
using the Pediatric Eosinophilic Esophagitis Symptom 
Severity Module (PEESS) total metric score from 
baseline (adolescent subjects only)
OLE Weeks 24, 
48, and beyond
Additional 
EoE 
Symptoms
Additional EoE symptoms reported on the modified Daily 
Symptom Diary (mDSD) evaluated by the distribution of 
subject responses regarding solid food avoidance, 
percentage of days solid food avoidance was due to EoE 
symptoms, percentage of days pain was associated with 
swallowing food, and the mean change in pain rating 
from baseline     
Baseline through 
OLE Week 24, 
Week 48, and 
Week 104
Health-related 
Quality of Life
Changes in health-related quality of life (HRQoL) 
assessed by the 12-Item Short Form Health Survey (SF-
12v2) in adult subjects and the10-Item Short Form Health 
Survey for Children (SF-10) in adolescent subjects from 
baseline
OLE Weeks 24 
and 48
Work 
Productivity
Changes in Work Productivity as assessed by the Work 
Productivity and Activity Impairment Questionnaire: 
Specific Health Problem (WPAI:SHP) from baseline 
(adult subjects only)
OLE Weeks 24 
and 48
PFS 
Administration
The proportion of subjects who successfully administer 
CC-93538 by the 
 pre-filled syringe 
(PFS), as assessed by the PFS Administration 
Questionnaire 
Through OLE 
Week 48
AI
Administration
The proportion of subjects who successfully administer 
CC-93538 by the 
 autoinjector (AI), as 
assessed by the AI Administration Questionnaire 
Through OLE 
Year 2 
Health Care 
Resource 
Utilization
The proportion of subjects with complications of EoE 
including but not limited to emergency department visits 
for food impaction, use of rescue therapy, or esophageal 
dilations
Through Safety 
Follow-up Visit
Biomarkers
CC-93538 treatment response as a function of baseline (as 
collected in Study CC-93538-EE-001) interleukin-13 (IL-
13) single nucleotide polymorphism (SNP) 
characterization
OLE Weeks 24 
and 48
Biomarkers
CC-93538 treatment response as a function of baseline 
and change from baseline in circulating biomarkers 
(including but not limited to periostin, eotaxin-3, and IL-
13)
OLE Weeks 24 
and 48
Biomarkers
CC-93538 treatment response as a function of baseline 
and change from baseline in esophageal tissue biomarkers 
(including but not limited to markers of epithelial 
mesenchymal transition [EMT], periostin, and eotaxin-3) 
OLE Weeks 24, 
48, and 104
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Protocol CC-93538-EE-002
Celgene International II Sàrl
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Final: 30 Jun 2023
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Table 2:
Study Endpoints
For OLE study endpoints, OLE baseline will be used.  In the Statistical Analysis Plan, baseline 
comparisons will be defined and additional subgroup analyses will be described.
Endpoint
Name
Description
Timeframe
Biomarkers
Exploratory measurements of severe acute respiratory 
syndrome coronavirus 2 (SARS-CoV-2) serology (anti-
SARS-CoV-2 total or immunoglobulin G [IgG]) from 
serum samples collected at Week 48 and annually 
thereafter and the potential association between these 
measurements and selected endpoints related to safety, 
efficacy, and/or biomarkers
OLE Week 48 and 
annually thereafter
Biomarkers
The mean change in esophageal distensibility as 
measured by EndoFLIP from baseline, if applicable
OLE Weeks 24, 
48, and 104
3
OVERALL STUDY DESIGN
3.1
Phase 3 Program Design
The Phase 3 program includes a multicenter, multinational, randomized, double-blind, placebo-
controlled induction and maintenance study to evaluate the efficacy and safety of CC-93538 in 
adult and adolescent subjects with EoE (Study CC-93538-EE-001) with a separate, optional Open-
label Extension study (OLE; Study CC-93538-EE-002).
An overview of the overall Phase 3 program design is presented in Figure 1.
Figure 1:
Overall Study Schema
Abbreviations:  EGD = esophagogastroduodenoscopy; EoE = eosinophilic esophagitis; IP = investigational product; 
N = sample size; OLE = Open-label Extension; SC = subcutaneous injection.
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3.2
Open-label Extension Study Design
The OLE study is a Phase 3, open-label, uncontrolled study to explore the long-term effects of 
treatment with CC-93538 360 mg SC once weekly in adult and adolescent subjects with EoE who 
had previously participated in the core Induction and Maintenance Study, CC-93538-EE-001.  
Approximately 259 subjects of the 399 subjects initially randomized in the core study, Study CC-
93538-EE-001, are expected to participate in the OLE study assuming an overall drop-out rate of 
35% in Study CC-93538-EE-001.  Along with approximately 239 adult subjects, approximately 
 adolescent subjects aged 12 to 17 years (at the time of screening in Study CC-93538-EE-001)
are expected to participate in the OLE study from the approximately 
subjects who are expected 
to enroll in the Induction Phase of the core study. In Austria, Germany, Spain, and Switzerland, 
adolescent subjects will not be enrolled.  Globally, subjects aged 12 to 75 years of age with a body 
weight of ≥ 40 kg (at the time of screening in Study CC-93538-EE-001) who have a diagnosis of 
EoE and who meet one of the following criteria with respect to participation in Study CC-93538-
EE-001 will be given the opportunity to participate in the OLE study.

Subjects who do not qualify for entry into the Maintenance Phase including:

Subjects who experience a severe EoE flare requiring endoscopic intervention and/or 
concomitant rescue therapy during the Induction Phase will be eligible for the OLE after 
completion of Week 24 of the Induction Phase

Subjects who complete Week 48 of the Maintenance Phase including:

Subjects who experience a severe EoE flare requiring endoscopic intervention and/or 
concomitant rescue therapy during the Maintenance Phase will be eligible for the OLE 
after completion of Week 48 of the Maintenance Phase.
In addition, approximately 
adult subjects aged 18 to 75 years old (inclusive, at the time of 
screening) will be enrolled in Study CC-93538-DDI-001, and up to 
 of these subjects who 
completed Period 2 in Study CC-93538-DDI-001 will also be given the opportunity to participate 
in the OLE study.
Refer to the Worsening of Symptoms, EoE flare, and the EoE Flare Assessment Visit Section and 
the Entry to Maintenance Phase Section of the CC-93538-EE-001 protocol for more details.  In 
addition, in order to participate in the OLE, subjects must not have been permanently discontinued 
from IP and must have demonstrated sufficient IP compliance in Study CC-93538-EE-001 and, in 
the opinion of the Investigator, must have experienced no clinically significant adverse events 
(AEs) related to IP that would preclude further dosing.  The OLE study includes an Open-label 
Treatment Period, an End of Treatment Visit at or after a minimum of 2 years of participation, and 
2 Safety Follow-up Visits as presented in Figure 2.
2.0
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930185673
2.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
49
Figure 2:
Open-label Extension Study Schema
This study will empanel a Steering Committee (Section 9.9.4) and safety monitoring will be 
performed by an external, independent Data Monitoring Committee (Section 9.9.3) in addition to 
routine internal review by the Safety Management Team (Section 9.9.2).
The study will be conducted in compliance with the International Council for Harmonisation (ICH) 
of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical 
Practice (GCP) and applicable regulatory requirements.
3.2.1
Open-label Treatment Period
Because subjects eligible for the OLE study have all participated in Study CC-93538-EE-001 or 
Study CC-93538-DDI-001, there will be no Screening Visit, and baseline assessments will be 
obtained from either the Induction Phase Week 24 Visit or the Maintenance Phase Week 48 Visit 
in Study CC-93538-EE-001 assessments, as applicable. For subjects who are entering the OLE 
after completion of Study CC-93538-DDI-001, most baseline assessments will be obtained in 
Study CC-93538-DDI-001 and a few additional assessments will be collected on OLE Day 1. 
Additional OLE baseline assessments not performed at the final Induction Phase (Week 24) or 
final Maintenance Phase (Week 48) Visits of Study CC-93538-EE-001 or Week 18/End of 
Treatment Visit of Study CC-93538-DDI-001 should be conducted at the OLE Day 1 Visit in 
accordance with the Table of Events (Table 3); it is anticipated that this should occur for most 
subjects on the same day.  Subjects will not be allowed to enroll in the OLE study and receive 
CC-93538 on OLE Day 1 if there will be a delay of > 21 days from dosing in Study CC-93538-
EE-001 or Study CC-93538-DDI-001 unless discussed with the Medical Monitor (refer to Section 
6.2).  The 2 Safety Follow-up Visits in Study CC-93538-EE-001/Study CC-93538-DDI-001 are 
not required for subjects enrolling in the OLE study.
The esophagogastroduodenoscopy (EGD) procedure should not be repeated at the OLE Day 1 
Visit, as long as this assessment was conducted at the final Induction or Maintenance Phase Visit
2.0
Approved
930185673
2.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
50
of Study CC-93538-EE-001 or prior to the End of Treatment Visit in Study CC-93538-DDI-001
(refer to Section 6.2).
During the Open-label Treatment Period, all subjects will be administered CC-93538 at a dose of 
360 mg SC once weekly for as long as they are participating in the study or until the Investigator 
decides to withdraw the subject or the Sponsor decides to terminate the study.  
Clinical laboratory tests, vital signs, physical examinations (including height and weight), 
pregnancy tests (female of childbearing potential [FCBP] subjects only), EGD, clinical symptom 
assessment, subject-reported outcomes, serum CC-93538 PK concentrations, serum antibodies to 
CC-93538 (to monitor for immunogenicity), concomitant medications, AE/SAE assessments, and 
relevant biomarker measurements in tissue biopsy and blood samples will be performed in 
accordance with the Table of Events (Table 3). 
3.2.2
End of Treatment and Safety Follow-up Visit
The OLE Treatment Period is a minimum of 2 years.  While the duration may continue longer as 
detailed in Section 3.3, the end of the Treatment Period will be individualized for each subject.  
Subjects may discontinue from the study at any time. Subjects who discontinue the study at or 
after 2 years of participation (ie, the Quarterly 4 Visit in Year 2 [Week 104]) will complete an End 
of Treatment (EoT) Visit (Section 6.2.4) within 2 weeks after their final dose of CC-93538 and an 
Interim 8-week and a Final 16-week Safety Follow-up Visit (Section 6.3.1) at 8 weeks and 
16 weeks, respectively, after the final dose of CC-93538 for the assessment of safety and clinical 
status. End of Treatment and Safety Follow-up assessments should be performed in accordance 
with the Table of Events (Table 3).  Subjects who discontinue the study before Week 104 will 
instead complete an Early Termination (ET) Visit.
3.2.3
Worsening of EoE Symptoms or Lack of Improvement
Subjects with a worsening of EoE symptoms during the study will be required to complete the EoE 
Flare Assessment Visit per the Table of Events (Table 3).  Subjects with increased signs and 
symptoms of EoE are instructed to contact the Investigator and/or study staff to determine if an 
EoE Flare Assessment Visit is warranted.
Any worsening of EoE symptoms during study participation will be documented as an EoE flare.  
See Section 6.4.2.7 and Section 6.2.3 for the protocol definition of EoE flare and EoE Flare 
Assessment Visit details, respectively.
During the course of the study, subjects who demonstrate a persistent lack of improvement or 
worsening of EoE symptoms should be evaluated if continuation of study treatment is appropriate.  
While subjects will have the opportunity to continue participation in the OLE with use of rescue 
therapy as needed, based on clinical judgment, the Investigator should discontinue any subject in 
which study participation no longer is in the best interest of the subject.  Subjects who are 
discontinued from the OLE study will be asked to complete an ET/EoT Visit (Section 6.2.4) and 
the 2 Safety Follow-up Visits (Section 6.3.1).
2.0
Approved
930185673
2.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
51
3.2.4
Planned Database Locks
There will be multiple planned database locks occurring at different time points of the study as 
follows:

The first planned lock will occur in conjunction with the primary lock of one of the parent
studies, CC-93538-EE-001, to support the Biologics License Application (BLA) submission.
Preliminary findings of the primary and secondary endpoints available up to the data cutoff 
date will be summarized in a clinical study report (CSR). The safety data collected up to the 
data cutoff date will also be integrated with other studies to create the integrated summary of 
safety.

The second planned database lock will occur approximately when all the subjects in the parent
Study CC-93538-EE-001 complete (or discontinue) the safety follow-up period, or 
approximately 4 months after the first lock. The purpose of the second lock is to support the 
4 month safety update during the regulatory review process.

The last planned lock is also the final database lock of the study. The triggering timing is when 
all the subjects complete the safety follow-up period or discontinue from the study 
prematurely. 
Additional ad hoc database locks may be considered upon the request of regulatory agencies.
3.3
Study Duration for Subjects
Subjects will begin participation in the OLE study on OLE Day 1 and following completion of all 
baseline assessments (including those obtained from either the Induction Phase Week 24 or the 
Maintenance Phase Week 48 Visit in Study CC-93538-EE-001, as applicable) will receive the first 
OLE dose of CC-93538.  Subjects will receive weekly doses of CC-93538 during the Open-label 
Treatment Period for a minimum duration of 2 years and will complete an EoT Visit within 2 
weeks after the final dose and an Interim 8-week Safety Follow-up Visit and a Final 16-week 
Safety Follow-up Visit at 8 and 16 weeks, respectively, after the final dose. Subjects may 
participate in the Open-label Treatment Period as early as completion of Week 24 of the Induction 
Phase of Study CC-93538-EE-001 or as late as following Week 48 of Study CC-93538-EE-001.
Subjects from Study CC-93538-DDI-001 will be offered an opportunity to enroll in the OLE Study 
CC-93538-EE-002 following completion of assessments in Period 2 through Week 18/End of 
Treatment Visit.
Individual subject participation in the OLE study will be for a minimum of 2 years but may extend 
for a longer duration.  Where applicable per local or national regulations, subjects may continue 
in the study until marketing approval (or marketing launch in Japan) is obtained in the country or 
the Sponsor discontinues the study, whichever comes first.
Subjects may continue participation as long as they tolerate treatment and are receiving benefit 
from participation in the study. Participation may continue until the subject decides to withdraw 
from the study, the subject meets any of the discontinuation criteria, the Investigator decides to 
withdraw the subject from the study, or the Sponsor decides to terminate the study (see 
Section 12.8). 
2.0
Approved
930185673
2.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
52
3.4
End of Study
The End of Study is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up (the Final 16-week Safety Follow-up Visit), 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 pre-specified in the protocol, whichever is the later date.  The OLE study duration is 
described in Section 3.3 above.
4
STUDY POPULATION
4.1
Number of Subjects 
It is anticipated that approximately 259 subjects of the 399 subjects initially randomized in Study 
CC-93538-EE-001 will participate in the OLE Study, CC-93538-EE-002.  Of these subjects, it is 
estimated that approximately 
adolescent subjects aged 12 to 17 years of the 
that are expected 
to enroll in the Induction Phase of Study CC-93538-EE-001 will participate in the OLE study.  The 
study population will consist of males and females aged 12 to 75 years (inclusive) with a diagnosis 
of EoE who have participated in the core Phase 3 Induction and Maintenance Study, CC-93538-
EE-001.  Subject age and inclusion in the adolescent age group will be based on age at the time of 
screening in Study CC-93538-EE-001.  Subjects who completed Week 48 of the Maintenance
Phase and subjects who experienced a severe EoE flare requiring endoscopic intervention and/or 
concomitant rescue therapy may be eligible to participate according to Study CC-93538-EE-001 
protocol pre-specified criteria and as outlined in Section 4.2, Inclusion Criterion 1.
Approximately 
subjects who were enrolled in Study CC-93538-DDI-001 who completed
assessments in Period 2 through Week 18/End of Treatment Visit and who meet all eligibility
criteria will also be offered an opportunity to enroll in the OLE Study CC-93538-EE-002.
Note:  In Study CC-93538-EE-001, countries or sites with local restrictions that prohibit 
enrollment of adolescents (aged 12 to 17 years inclusive) will only enroll subjects who are 18 years 
of age or older.  Enrollment of adolescent subjects will begin only after the applicable regulatory 
requirements for enrolling subjects in that age group have been satisfied and the necessary health 
authority and Ethics Committee approvals have been granted.  Where national or regional 
guidelines for the definition of adolescence differ from the definition stated above, the national or 
regional guidelines may be used to determine eligibility.  In Austria, Germany, Spain, and 
Switzerland, adolescent subjects will not be enrolled.
Subjects will be re-consented/assented for the OLE study. To be eligible for the OLE study, 
subjects must have qualified for the core Phase 3 Induction and Maintenance Study CC-93538-
EE-001 or the Phase 1 Study CC-93538-DDI-001 and must meet the eligibility criteria below.
4.2
Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the study:
1)
a.
Subject must have participated in Study CC-93538-EE-001, and meets one of the
following criteria:
2.0
Approved
930185673
2.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
53
1. Subject experienced a severe EoE flare requiring endoscopic intervention and/or 
concomitant rescue therapy during the Induction Phase and has completed Week 24 of 
the Induction Phase; OR
2. Subject completed the Induction Phase and does not qualify for entry to the 
Maintenance Phase for reasons other than a severe EoE flare; OR
3. Subject experienced a severe EoE flare requiring endoscopic intervention and/or 
concomitant rescue therapy during the Maintenance Phase and completed Week 48 of 
the Maintenance Phase; OR
4. Subject completed Week 48 of the Maintenance Phase; 
b. OR Subject must have participated in Study CC-93538-DDI-001 and completed
assessments in Period 2 through Week 18/End of Treatment Visit.
2)
Subject must have had ≥80% and ≤ 120% overall compliance of IP use in Study CC-93538-
EE-001 or Study CC-93538-DDI-001, and subject must not have been permanently 
discontinued from IP while participating in Study CC-93538-EE-001 or Study CC-93538-
DDI-001.
3)
Subject must have, in the opinion of the Investigator, experienced no clinically significant 
AEs related to IP in Study CC-93538-EE-001 or Study CC-93538-DDI-001 that would 
preclude further dosing.
4)
Female subject 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; and 2) has not undergone a hysterectomy or bilateral oophorectomy or bilateral 
salpingectomy; 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). An FCBP must:
a.
Have 2 negative pregnancy tests as verified by the Investigator prior to starting study 
therapy in Study CC-93538-EE-001 or Study CC-93538-DDI-001 and an additional 
negative result prior to continuing study therapy in the OLE. She must agree to ongoing 
pregnancy testing during the course of the study and through the Final 16-week Safety 
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 and as applicable per national and local regulations (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]): 
* 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.
2.0
Approved
930185673
2.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
54

combined hormonal (estrogen and progestogen containing) contraception, which 
may be oral, intravaginal, or transdermal
Note: Intravaginal and transdermal combined hormonal contraception are not 
approved in Japan and would therefore not be an acceptable method of 
contraception for subjects enrolled in this region.

progestogen-only hormonal contraception associated with inhibition of ovulation, 
which may be oral, injectable, or implantable
Note: progestogen-only hormonal contraception is not approved in Japan and 
would therefore not be an acceptable method of contraception for subjects enrolled 
in this region.

placement of an intrauterine device (IUD)

placement of an intrauterine hormone-releasing system (IUS)

bilateral tubal ligation; or bilateral tubal occlusion (if an implantable device was 
recently placed, the subject must use an additional effective method of birth control 
until full occlusion has been confirmed and documented)    

vasectomized partner (vasectomized partner is a highly effective birth control 
method provided that the partner is the sole sexual partner of the FCBP and has 
received medical assessment of the surgical success)

sexual abstinence
5) Subject who is an FCBP must have a negative urine or serum pregnancy test prior to dosing 
on OLE Day 1.
6) Subject is willing to receive weekly SC injections throughout the study.
7) Subject (18 years of age or older) must understand and voluntarily sign an informed 
consent form (ICF) prior to any study-related assessments/procedures being conducted. For 
subjects less than 18 years of age, subject assent must be obtained, and parental/legal 
representative consent is required.  Adolescent subjects who reach the legal age of consent 
while participating in the study will be asked to sign an ICF (called a Transitional ICF) 
themselves to acknowledge their willingness to continue in the study.  In Austria, Germany, 
Spain, and Switzerland, adolescent subjects will not be enrolled.
8) Subject is willing and able to adhere to the study visit schedule and other protocol 
requirements.
4.3
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
1) Subject has clinical or endoscopic evidence of the presence of any other disease that may 
interfere with or affect the histologic, endoscopic, and clinical symptom endpoints for this 
study (eg, erosive esophagitis Los Angeles [LA] classification Grade B or above, Barrett's 
esophagus, esophageal lichen planus, upper gastrointestinal bleed, achalasia, Schatzki’s 
rings, inflammatory bowel disease, diagnosed eosinophilic gastritis and/or duodenitis
[clinical symptoms and/or EGD findings and confirmatory eosinophilia in gastric and/or
duodenal mucosa], or significant hiatal hernia [> 3 cm], etc.); or history of fundoplication.  
2) Subject demonstrates presence of esophageal varices.
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930185673
2.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
55
3) Subject has a known active Helicobacter pylori infection and/or is currently being treated 
for this condition. 
4) Subject demonstrates evidence of immunosuppression or is receiving systemic 
immunosuppressive or immunomodulating drugs (including but not limited to, Janus 
kinase [JAK] inhibitors, phosphodiesterase-4 [PDE-4] inhibitors, anti-interleukin [IL]-13 
[IL-13] antibodies [except IP in this study], IL-4 receptor alpha antagonist antibodies [eg, 
dupilumab], anti-IL-5 antibodies, anti-IL-17 antibodies, anti-immunoglobulin E [IgE]
antibodies, α4β7 integrin inhibitor antibodies, or any other monoclonal antibody, 
methotrexate, cyclosporine, azathioprine, mercaptopurine, interferon alpha [IFNα], tumor 
necrosis factor alpha [TNFα] inhibitors, etc) within 5 drug half-lives prior to OLE Day 1. 
Any use of these medications will be prohibited during the study.  
5) Subject has received oral or sublingual immunotherapy within 6 months of OLE Day 1; 
any use will be prohibited during the study. 
6) Subject received an IP, including through participation in an interventional trial for 
COVID-19, other than the IP administered in Study CC-93538-EE-001 or Study CC-
93538-DDI-001 within 5 half-lives prior to OLE Day 1 or plans to receive another IP
during the study.  Subjects who received an investigational COVID-19 vaccine as part of 
a clinical trial during the course of Study CC-93538-EE-001 or Study CC-93538-DDI-001 
will not be eligible to participate unless it is determined by discussion between Investigator 
and the Clinical Trial Physician that the biologic impact of the vaccine is stabilized.
7) Subject received a live attenuated vaccine within one month prior to OLE Day 1 or 
anticipates the need to be vaccinated with a live attenuated vaccine during the course of the 
study.  Administration of any live (including attenuated) vaccine will be prohibited during 
the study through the Final 16-week Safety Follow-up Visit.
8) Subject has any other disease that would make conduct of the protocol or interpretation of 
the study results difficult or that would put the prospective subject at risk by participating 
in the study (eg, severe uncontrolled asthma, infection causing eosinophilia, 
hypereosinophilic syndrome; a documented medical diagnosis of gastritis, which is 
clinically significant in the judgment of the Investigator; colitis, celiac disease, Mendelian 
disorder associated with EoE, or cardiovascular condition, or neurologic or psychiatric 
illness that compromises the prospective subject's ability to accurately document symptoms 
of EoE).
9) Subject has an active parasitic/helminthic infection or a suspected parasitic/helminthic 
infection.  Subjects with suspected infections may participate if clinical and laboratory 
assessments, if needed, rule out active infection prior OLE Day 1. 
10) Subject has a chronic infection (eg, hepatitis B or C, human immunodeficiency virus 
[HIV], or tuberculosis as defined by standard medical guidelines).
11) Subject is pregnant or lactating.
12) Subject has developed 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 IP is also 
exclusionary.
13) Subject has a newly diagnosed malignancy or lymphoproliferative disease.
2.0
Approved
930185673
2.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
56
14) Subject has a history of alcohol or drug abuse diagnosed within 5 years prior to Study CC-
93538-EE-001 or Study CC-93538-DDI-001 participation.
15) Subject has any significant medical condition, laboratory abnormality, or psychiatric 
illness that would prevent the subject from participating in the study.
16) Subject has any condition including the presence of laboratory abnormalities, which places 
the subject at unacceptable risk if he/she were to participate in the study.
17) Subject has any condition that confounds the ability to interpret data from the study.
2.0
Approved
930185673
2.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
57
5
TABLE OF EVENTS
Table 3:
Table of Events for the Open-label Extension Study
Study Procedures
Base
-linea
Open-label Extension Treatment Period Year 1
Open-label Extension Treatment 
Period Year 2 and Beyondb
AI 
Visity
EoE 
Flare 
Visitc
ET/ 
EoT
Visitd
Interim 
8-week 
Safety 
Follow-
up Visit
Final 
16-
week 
Safety 
Follow
-up 
Visit
Visit Label
(Q = Quarterly)
OLE
Visit 
1
OLE
Visit 
2
OLE
Visit 3
OLE
Visit 4
OLE
Visit 5
OLE
Visit 6
OLE
Visit 7
OLE
Q1 
Visits
OLE
Q2 
Visits
OLE
Q3 
Visits
OLE
Q4 
Visits
Visit Week 
(Window)
OLE 
Day
1
OLE 
Week 
4 
(Day 
29
±3d)
OLE 
Week
8 
(Day 
57
±7d)
OLE 
Week
16
(Day 
113
±7d)
OLE 
Week
24
(Day 
169
±7d)
OLE 
Week
36
(Day 
253
±7d)
OLE 
Week
48
(Day
337
±7d)
End of 
Quarter
1
(Year x 
+ wk 13 
[±14d])
Mid-
point 
of 
Year 
(Year 
x + wk 
26  
[±14d])
End of 
Quarter
3 
(Year x 
+ wk 39 
[± 14d])
End of 
Year
(Year x 
+wk 52 
[±14d])
Within 
2 weeks 
After 
Final 
Dose
8 Weeks 
After 
Final 
Dose 
(±7d)
16 
Weeks
After 
Final 
Dose 
(±7d)
Informed consent/ 
assent
X
Inclusion/exclusion 
criteria and confirm 
eligibility
X
Confirm prior 
therapy
X
Concomitant 
therapy
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AEs/SAEse
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematology and 
chemistryf
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysisf
X
X
X
X
X
X
X
X
X
X
Pregnancy test 
(FCBP only)g
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical 
examinationh
X
X
X
X
X
X
X
X
X
X
X
X
X
X
2.0
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930185673
2.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
58
Table 3:
Table of Events for the Open-label Extension Study
Study Procedures
Base
-linea
Open-label Extension Treatment Period Year 1
Open-label Extension Treatment 
Period Year 2 and Beyondb
AI 
Visity
EoE 
Flare 
Visitc
ET/ 
EoT
Visitd
Interim 
8-week 
Safety 
Follow-
up Visit
Final 
16-
week 
Safety 
Follow
-up 
Visit
Visit Label
(Q = Quarterly)
OLE
Visit 
1
OLE
Visit 
2
OLE
Visit 3
OLE
Visit 4
OLE
Visit 5
OLE
Visit 6
OLE
Visit 7
OLE
Q1 
Visits
OLE
Q2 
Visits
OLE
Q3 
Visits
OLE
Q4 
Visits
Visit Week 
(Window)
OLE 
Day
1
OLE 
Week 
4 
(Day 
29
±3d)
OLE 
Week
8 
(Day 
57
±7d)
OLE 
Week
16
(Day 
113
±7d)
OLE 
Week
24
(Day 
169
±7d)
OLE 
Week
36
(Day 
253
±7d)
OLE 
Week
48
(Day
337
±7d)
End of 
Quarter
1
(Year x 
+ wk 13 
[±14d])
Mid-
point 
of 
Year 
(Year 
x + wk 
26  
[±14d])
End of 
Quarter
3 
(Year x 
+ wk 39 
[± 14d])
End of 
Year
(Year x 
+wk 52 
[±14d])
Within 
2 weeks 
After 
Final 
Dose
8 Weeks 
After 
Final 
Dose 
(±7d)
16 
Weeks
After 
Final 
Dose 
(±7d)
Height (adolescents 
only after OLE Day 
1)
X
X
X
X
X
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum antibodies to 
CC-93538f,i
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum CC-93538 
PK assessmentf
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Circulating 
biomarkers 
assessmentf,j
X
X
X
X
X
X
SARS-CoV-2 
serologyk
X
X
X
X
Phone call 
reminderl
X
X
X
Modified Daily 
Symptom Diary 
(mDSD)m
X
X
X
X
X
X
X
2.0
Approved
930185673
2.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
59
Table 3:
Table of Events for the Open-label Extension Study
Study Procedures
Base
-linea
Open-label Extension Treatment Period Year 1
Open-label Extension Treatment 
Period Year 2 and Beyondb
AI 
Visity
EoE 
Flare 
Visitc
ET/ 
EoT
Visitd
Interim 
8-week 
Safety 
Follow-
up Visit
Final 
16-
week 
Safety 
Follow
-up 
Visit
Visit Label
(Q = Quarterly)
OLE
Visit 
1
OLE
Visit 
2
OLE
Visit 3
OLE
Visit 4
OLE
Visit 5
OLE
Visit 6
OLE
Visit 7
OLE
Q1 
Visits
OLE
Q2 
Visits
OLE
Q3 
Visits
OLE
Q4 
Visits
Visit Week 
(Window)
OLE 
Day
1
OLE 
Week 
4 
(Day 
29
±3d)
OLE 
Week
8 
(Day 
57
±7d)
OLE 
Week
16
(Day 
113
±7d)
OLE 
Week
24
(Day 
169
±7d)
OLE 
Week
36
(Day 
253
±7d)
OLE 
Week
48
(Day
337
±7d)
End of 
Quarter
1
(Year x 
+ wk 13 
[±14d])
Mid-
point 
of 
Year 
(Year 
x + wk 
26  
[±14d])
End of 
Quarter
3 
(Year x 
+ wk 39 
[± 14d])
End of 
Year
(Year x 
+wk 52 
[±14d])
Within 
2 weeks 
After 
Final 
Dose
8 Weeks 
After 
Final 
Dose 
(±7d)
16 
Weeks
After 
Final 
Dose 
(±7d)
Patient Global 
Impression of 
Severity (PGI-S)
X
X
X
X
X
X
X
X
Clinician Global 
Impression of 
Severity (CGI-S)
X
X
X
X
X
X
X
X
Global Impression 
of Change in EoE 
Symptoms (GIC-
EoE)v
X
X
X
X
Xn
Xn
Eosinophilic 
Esophagitis Activity 
Index (EEsAI)
X
X
X
X
X
X
X
X
Pediatric 
Eosinophilic 
Esophagitis 
Symptom Severity 
Module (PEESS; 
adolescents only)
X
X
X
X
X
X
X
X
2.0
Approved
930185673
2.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
60
Table 3:
Table of Events for the Open-label Extension Study
Study Procedures
Base
-linea
Open-label Extension Treatment Period Year 1
Open-label Extension Treatment 
Period Year 2 and Beyondb
AI 
Visity
EoE 
Flare 
Visitc
ET/ 
EoT
Visitd
Interim 
8-week 
Safety 
Follow-
up Visit
Final 
16-
week 
Safety 
Follow
-up 
Visit
Visit Label
(Q = Quarterly)
OLE
Visit 
1
OLE
Visit 
2
OLE
Visit 3
OLE
Visit 4
OLE
Visit 5
OLE
Visit 6
OLE
Visit 7
OLE
Q1 
Visits
OLE
Q2 
Visits
OLE
Q3 
Visits
OLE
Q4 
Visits
Visit Week 
(Window)
OLE 
Day
1
OLE 
Week 
4 
(Day 
29
±3d)
OLE 
Week
8 
(Day 
57
±7d)
OLE 
Week
16
(Day 
113
±7d)
OLE 
Week
24
(Day 
169
±7d)
OLE 
Week
36
(Day 
253
±7d)
OLE 
Week
48
(Day
337
±7d)
End of 
Quarter
1
(Year x 
+ wk 13 
[±14d])
Mid-
point 
of 
Year 
(Year 
x + wk 
26  
[±14d])
End of 
Quarter
3 
(Year x 
+ wk 39 
[± 14d])
End of 
Year
(Year x 
+wk 52 
[±14d])
Within 
2 weeks 
After 
Final 
Dose
8 Weeks 
After 
Final 
Dose 
(±7d)
16 
Weeks
After 
Final 
Dose 
(±7d)
Health-related 
quality of life (SF-
12v2 in adults; SF-
10 in adolescents)
X
X
X
Xo
Work Productivity 
and Activity Index 
(WPAI:SHP; adults 
only)
X
X
X
Xp
Health resource 
utilization
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AI Administration 
Questionnairew
X
X
X
X
X
X
X
X
X
EGD with tissue 
biopsiesq
X
X
X
Xr
Xs
Xt
EoE Endoscopic 
Reference Score 
(EREFS)
X
X
X
Xr
Xs
Xt
Informed 
consent/assent for 
EndoFLIP sub-
study, if applicable
X
2.0
Approved
930185673
2.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
61
Table 3:
Table of Events for the Open-label Extension Study
Study Procedures
Base
-linea
Open-label Extension Treatment Period Year 1
Open-label Extension Treatment 
Period Year 2 and Beyondb
AI 
Visity
EoE 
Flare 
Visitc
ET/ 
EoT
Visitd
Interim 
8-week 
Safety 
Follow-
up Visit
Final 
16-
week 
Safety 
Follow
-up 
Visit
Visit Label
(Q = Quarterly)
OLE
Visit 
1
OLE
Visit 
2
OLE
Visit 3
OLE
Visit 4
OLE
Visit 5
OLE
Visit 6
OLE
Visit 7
OLE
Q1 
Visits
OLE
Q2 
Visits
OLE
Q3 
Visits
OLE
Q4 
Visits
Visit Week 
(Window)
OLE 
Day
1
OLE 
Week 
4 
(Day 
29
±3d)
OLE 
Week
8 
(Day 
57
±7d)
OLE 
Week
16
(Day 
113
±7d)
OLE 
Week
24
(Day 
169
±7d)
OLE 
Week
36
(Day 
253
±7d)
OLE 
Week
48
(Day
337
±7d)
End of 
Quarter
1
(Year x 
+ wk 13 
[±14d])
Mid-
point 
of 
Year 
(Year 
x + wk 
26  
[±14d])
End of 
Quarter
3 
(Year x 
+ wk 39 
[± 14d])
End of 
Year
(Year x 
+wk 52 
[±14d])
Within 
2 weeks 
After 
Final 
Dose
8 Weeks 
After 
Final 
Dose 
(±7d)
16 
Weeks
After 
Final 
Dose 
(±7d)
EndoFLIP 
(optional sub-
study)x
X
X
X
Xr
CC-93538 
administrationu
X
X
X
X
X
X
X
X
X
X
X
X
Abbreviations: AE = adverse event; AI = autoinjector; CGI-S = Clinician Global Impression of Severity; d = day; EEsAI = Eosinophilic Esophagitis Activity 
Index; EGD = esophagogastroduodenoscopy; EoE = eosinophilic esophagitis; EREFS = EoE Endoscopic Reference Score; EoT = End of Treatment; ET: Early 
Termination; FCBP = females of childbearing potential; GIC-EoE = Global Impression of Change in EoE Symptoms; IgG = immunoglobulin G; IP = investigational 
product; mDSD = modified Daily Symptom Diary; OLE = Open-label Extension; PEESS = Pediatric Eosinophilic Esophagitis Symptom Severity Module; PGI-S 
= Patient Global Impression of Severity; PK = pharmacokinetic; Q = quarterly; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome 
coronavirus 2; SC = subcutaneous; SF-10 = 10-Item Short Form Health Survey for Children; SF-12v2 = 12-Item Short Form Health Survey; WPAI:SHP = Work 
Productivity and Activity Impairment Questionnaire: Specific Health Problem.
a All OLE Day 1 study procedures/assessments will serve as baseline assessments and will be completed prior to dosing unless otherwise noted.  For subjects 
transitioning from Study CC-93538-EE-001, the OLE Day 1/Baseline assessments will include the Induction Phase Week 24 Visit assessments, or Maintenance
Week 48 Visit assessments from Study CC-93538-EE-001, as applicable, as the transition from Study CC-93538-EE-001 to the OLE study is anticipated to 
occur on the same day for most subjects. Additional OLE baseline assessments not performed at the final Induction Phase (Week 24) or Maintenance Phase 
(Week 48) Visit should be conducted (or repeated) at the OLE Day 1 Visit. The EGD procedure should not be repeated at the OLE Day 1 Visit, with the 
exception as noted in Section 6.2. OLE Day 1/Baseline refers to any visit during which OLE baseline assessments are obtained, including the Induction Phase 
Week 24 Visit, or Maintenance Phase Week 48 Visit, or OLE Day 1.  For subjects transitioning from Study CC-93538-DDI-001, OLE Day 1/Baseline refers to 
any visit during which OLE baseline assessments are obtained, including the End of Treatment Visit from Study CC-93538-DDI-001 or OLE Day 1 (in Study 
CC-93538-EE-002); the following baseline assessments will be performed at OLE Day 1, for these were not evaluated in the parent study: PGI-S, CGI-S, SF-
2.0
Approved
930185673
2.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
62
12v2, WPAI, and circulating biomarkers assessment. Subjects will not be allowed to enroll in the OLE study and receive CC-93538 on OLE Day 1 if there will 
be a delay of > 21 days from dosing in Study CC-93538-EE-001 or Study CC-93538-DDI-001 unless discussed with the Medical Monitor (refer to Section 6.2).
b After completion of Week 48 (Visit 7) plus an additional 4 weeks in the OLE Treatment Period (that is, after Week 52 of the OLE study), subjects will continue 
on into the second year of the OLE (Year 2 and beyond).  During Year 2 and beyond, subjects will attend study visits every 13 weeks (±14 days) for a total of 4
quarterly study visits each year within a 52-week per year format.  For each year of participation after Week 52, the Quarterly 1 Visit, Quarterly 2 Visit, Quarterly 
3 Visit, and Quarterly 4 Visit will be completed.  The Quarterly 2 and 4 Visits include additional assessments not conducted in the Quarterly 1 and 3 Visits.
c An EoE Flare Assessment Visit should be scheduled as close as possible to the time when an EoE flare is suspected.
d Subjects who discontinue study treatment at any time during the OLE will be asked to complete either an ET Visit, if discontinuation occurs before the Quarterly 
4 Visit at the end of Year 2 (Week 104), or an EoT Visit, if discontinuation occurs at or after the Quarterly 4 Visit at the end of Year 2 (Week 104).  The visit 
will occur within 2 weeks after the final dose of CC-93538.
e The timing of AE/SAE assessment documentation for the OLE study will begin at the time of or after the first dose in the OLE study (on OLE Day1); AE/SAEs 
occurring before this timeframe will be documented in Study CC-93538-EE-001 or Study CC-93538-DDI-001.  Ongoing AE/SAEs first documented in Study 
CC-93538-EE-001 or Study CC-93538-DDI-001 will continue to be followed in the OLE study.
f
Pre-dose assessments except for the ET/EoT Visit and 2 Safety Follow-up Visits.  
g For females of childbearing potential (FCBP), a urine (or serum) pregnancy test must be performed at OLE Day 1/Baseline and the results reviewed on OLE 
Day 1 prior to the first OLE CC-93538 dose.  A pregnancy test does not need to be repeated if it has been conducted at the final visit in Study CC-93538-EE-
001 or Study CC-93538-DDI-001, and OLE Day 1 occurs on the same day (See Section 6.2). Urine pregnancy tests will be done at subsequent visits.  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 all study visits, the Investigator 
will counsel FCBP subjects on pregnancy precautions for the duration of the study.
h Complete physical examination will be performed at OLE Day 1, Week 24, Week 48, at the Quarterly 4 Visit, at the ET/EoT Visit, and at the 2 Safety Follow-
up Visits; abbreviated physical examination will be performed at Weeks 4, 8, 16, 36, and at the Quarterly 1, 2, and 3 Visits.
i
If anti-drug antibodies (ADAs) are detected, they will be further characterized as to whether the ADAs are neutralizing or not in nature. 
j
Blood samples will be obtained to evaluate levels of various circulating biomarkers, including but not limited to periostin, eotaxin-3, and IL-13.  
k Serum will be collected at OLE Day 1, Week 48, at the Quarterly 4 Visit, and at the ET/EoT 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 (see Section 6.7.1).
l
A phone call will be made to subjects as a reminder to complete the mDSD.  The Table of Events X’s are noted in the visit before the start of the collection
period in order to alert sites to the upcoming interim visit activity.  Phone calls will take place just prior to the beginning of the 14-day mDSD data collection
period for Week 24 (just prior to Week 22) and for Week 48 (just prior to Week 46). Additionally, for the end of Year 2 assessments, a phone call will take place
within a couple of days prior to Week 100 as a reminder for the beginning of the 4-week mDSD collection period, as well as within a couple of days prior to the
Week 102 as a reminder for the start of the 14-day mDSD collection period prior to Week 104 (the Quarterly 4 Visit at the end of Year 2).
m The mDSD will be completed daily after the last meal of the day prior to OLE Day 1/Baseline as required in Study CC-93538-EE-001 or as required in Study 
CC-93538-DDI-001, daily from OLE Day 1 through Week 24, for 4 consecutive weeks (28 days) prior to the Week 48 Visit, and for 4 consecutive weeks
(28 days) prior to the Quarterly 4 Visit at the end of Year 2 (Week 104).
n The GIC-EoE will only be collected at the ET Visit if at or before Week 48 and at the EoE Flare Visit occurring at or before Week 48, if applicable.
o The SF-12v2 in adults and SF-10 in adolescents will only be collected at the ET Visit if at or before Week 48.
p The WPAI:SHP in adults will only be collected at the ET Visit if at or before Week 48.
2.0
Approved
930185673
2.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
63
q The EGD biopsies will be measured for relevant tissue biomarkers when possible.  Esophageal tissue biomarkers will not be assessed in subjects transitioning 
from Study CC-93538-DDI-001.
r
Following the Week 48 time point, EGD is scheduled at one additional time point, at the Quarterly 4 Visit occurring at Week 104 (end of Year 2) but is not 
required if an EGD was performed within 24 weeks of the Week 104 Visit. 
s
The EGD is not required at EoE Flare Assessment Visits; if conducted, data should be collected when available, and if feasible, a sample may be collected and 
sent to the central reader.
t
The EGD will be completed at the ET Visit if the visit occurs before or at Week 48 but is not required if within 8 weeks since the last EGD.  The EGD is not 
required at ET Visits after Week 48.
u All subjects will receive weekly open-label CC-93538 360 mg during the OLE. Subjects will be given their first dose of CC-93538 at the OLE Day 1 Visit 
(which is anticipated to be the same day as the Induction Phase Week 24 Visit or Maintenance Phase Week 48 Visit in Study CC-93538-EE-001 for most subjects
and may occur on the same day as the End of Treatment Visit in Study CC-93538-DDI-001 if it has been at least 7 days from the last CC-93538 dose). Subjects 
will then receive weekly doses throughout the Open-label Treatment Period for a minimum of 2 years or as long as they are participating in the study.  The first 
3 weekly SC doses (OLE Day 1, Week 1, and Week 2) will be required to be given in the clinic, and subjects will remain in the clinic for at least 30 minutes 
following dosing for observation.  Additionally, the Investigator will review the importance of IP compliance and evaluate compliance for each subject in 
accordance with the protocol. To ensure accurate dose administration and compliance with the new 
 weekly SC injection using the 
 
AI presentation, for subjects who did not begin the study with the new 
presentation (on OLE Day 1), one additional in-clinic weekly dose with at 
least a 30-minute observation is required for the first administration. This first dose will occur either at the time of the subject’s next scheduled protocol required 
study visit or the First AI Administration Visit.
v GIC-EoE will only be completed in subjects transitioning from Study CC-93538-EE-001.
w The AI Administration Questionnaire will be conducted only in subjects who self-administer (as defined as per Section 7.2.1) with the new 
 
injection CC-93538 
 AI presentation. For in-clinic administration, the subject or caregiver should provide responses to the questionnaire 
immediately after dosing.  For at home administration, the study staff will contact the subject/caregiver by phone within 24 hours of dose administration.  In-
clinic assessments include the first in-clinic dose (OLE Day 1 or applicable week), Week 8, Week 24, and Week 48 of Year 1, and the Quarterly 1 Visit, 
Quarterly 2 Visit, Quarterly 3 Visit, and Quarterly 4 Visit in Year 2 as applicable.  In addition to the X’s denoted in the Table of Events for the in-clinic 
assessments, additional time points to capture at home dosing include the first weekly dose at home (Week 3 or the applicable week), Week 6, Week 20, and 
Week 44 in Year 1, and Week 60, Week 72, Week 84, and Week 96 in Year 2, as applicable. Further, for subjects who receive their first dose of the AI at the 
“First Administration Visit” the AI Administration Questionnaire will be conducted.  If a time point is missed, the questionnaire can be administered at the 
next weekly dose for the respective condition (in-clinic visit or at home administration).
x Only subjects transitioning from Study CC-93538-EE-001 and who have participated in the sub-study during enrollment in Study CC-93538-EE-001 are eligible 
to participate.
y A First AI Administration Visit will be required for subjects whose next scheduled protocol visit is not within 4 weeks of Protocol Amendment 2 site approval
and IP availability. The visit may be scheduled at any time within this 4-week period. 
2.0
Approved
930185673
2.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
64
6
PROCEDURES
Assessments and procedures for OLE Day 1 (Baseline), the OLE Treatment Period and the 2 Safety 
Follow-up Visits are outlined in Table 3. Study assessments and procedures are described in 
Section 6.2 and Section 6.3. The day of administration of the first dose of CC-93538 is defined as 
OLE Day 1.
It is recommended that the study visits are scheduled in the morning. Whenever possible, the
assessment order sequence should remain constant and should be conducted at approximately the 
same time of day throughout the study.
The following order for performing assessments and procedures is recommended (note that not all 
assessment and procedures are performed at every visit): 

EoE clinical symptom assessment instruments and subject-reported outcomes

Spontaneous or solicited AE reporting

Vital signs

Physical examination

Clinical laboratory tests, including blood sampling for the assessment of serum CC-93538 PK 
concentrations, anti-drug antibodies (ADAs), and biomarkers

Esophagogastroduodenoscopy (EGD) (if applicable)

IP administration
Throughout the study, IP administration should occur on the same day each week.  For 
administration on study visit days, dosing should occur in the clinic.  In the event a study visit can 
only be scheduled on a different day of the week than the usual dosing day, subjects should 
maintain their usual dosing schedule when possible.  
For the purposes of this study, adolescents are defined as subjects aged 12 to 17 years at the time 
of signing the assent form in Study CC-93538-EE-001 (except where national or regional 
guidelines for the definition of adolescence differ from the definition stated above) and adults are 
defined as subjects aged 18 to 75 years at the time of signing the ICF in Study CC-93538-EE-001.  
Subjects who enter the study as adolescents should continue to complete the assessments specific 
for adolescents throughout the study and do not need to complete assessments that are only 
required in adult subjects.  In Austria, Germany, Spain, and Switzerland, adolescent subjects will 
not be enrolled.
Any questions regarding the protocol should be directed to the Celgene Medical Monitor or 
designee. 
6.1
Screening Period
There is no Screening Period for the OLE study. Subject eligibility is described in Section 4.2 and 
Section 4.3. Baseline assessments are described in Section 6.2.
2.0
Approved
930185673
2.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
65
6.2
Open-label Extension Treatment Period
The OLE Day 1/Baseline assessments shown in Table 3 will be completed prior to the first dose 
of CC-93538 in the OLE study. For subjects transitioning from Study CC-93538-EE-001, OLE 
Day 1/Baseline refers to any visit during which OLE baseline assessments are obtained, including 
the following visits from Study CC-93538-EE-001:  Induction Phase Week 24 Visit or the 
Maintenance Phase Week 48 Visit, or OLE Day 1 (in Study CC-93538-EE-002). Transition to the 
OLE study should occur for most subjects on the same day as the Induction Phase Week 24 or the 
Maintenance Phase Week 48 Visit.  For subjects transitioning from Study CC-93538-DDI-001, 
OLE Day 1/Baseline refers to any visit during which OLE baseline assessments are obtained, 
including the End of Treatment Visit from Study CC-93538-DDI-001 or OLE Day 1 (in Study 
CC-93538-EE-002).  The OLE Day 1 Visit may occur on the same day as the End of Treatment 
Visit if it has been at least 7 days from the last CC-93538 dose in the parent study.
However, for select assessments, baseline will be evaluated at earlier time points in Study 
CC-93538-DDI-001 (prior to End of Treatment) and no assessment will be conducted on OLE 
Day 1.  These include EGD with tissue biopsies, EoE Endoscopic Reference Score (EREFS), and 
Eosinophilic Esophagitis Activity Index (EEsAI); assessments will continue in the OLE at post-
baseline time points.  
Importantly, for subjects transitioning from Study CC-93538-DDI-001, the following baseline 
assessments will be performed at OLE Day 1, for these were not evaluated in the parent study:

Patient Global Impression of Severity (PGI-S)

Clinician Global Impression of Severity (CGI-S)

12-Item Short Form Health Survey (SF-12v2)

Work Productivity and Activity Impairment Questionnaire: Specific Health Problem
(WPAI:SHP)

Circulating biomarkers assessment
Lastly, not all assessments will be required at baseline or during the study for subjects transitioning 
from Study CC-93538-DDI-001:  Global Impression of Change in EoE Symptoms (GIC-EoE), 
esophageal tissue biomarkers, and EndoFLIP will not be conducted in these subjects, as no 
baseline assessment will be available.
Subjects entering the OLE study will not complete the Safety Follow-up Visits in Study CC-
93538-EE-001 or Study CC-93538-DDI-001.  The Investigator will review all available 
information to confirm that the subject continues to meet all study enrollment criteria and will 
complete the additional OLE Day 1 activities for confirmation of eligibility. Written, signed, and 
dated informed consent/assent from the subject prior to the performance of any study related 
procedures not already completed for the Week 24 or Week 48 Visit in Study CC-93538-EE-001 
or at the End of Treatment Visit (or prior to End of Treatment) in Study CC-93538-DDI-001 must 
be obtained by the Principal Investigator or designee (refer to Section 12.3 for further details 
2.0
Approved
930185673
2.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
66
regarding obtaining subjects informed consent/assent).  A copy of the signed informed 
consent/assent must be given to the subject for his/her records.
The following evaluations/activities will be performed as specified in Table 3:

Additional OLE Day 1 activities include informed consent/assent, confirmation that subjects 
qualified for and participated in Study CC-93538-EE-001 or Study CC-93538-DDI-001, 
review of CC-93538-EE-002 inclusion/exclusion criteria and confirmation of eligibility, AE
assessment, health resource utilization monitoring, and review and documentation of any prior 
and concomitant therapies that began within 28 days of OLE Day 1.

The baseline assessments will include those conducted for the Induction Phase Week 24 Visit 
or Maintenance Phase Week 48 Visit in Study CC-93538-EE-001, as applicable, or those 
conducted at the End of Treatment Visit (or prior to End of Treatment) in Study CC-93538-
DDI-001, as applicable. Additional OLE baseline assessments not performed at the final 
Induction Phase (Week 24) or Maintenance Phase (Week 48) Visit in Study CC-93538-EE-
001 or that are required on OLE Day 1 for subjects who participated in Study CC-93538-DDI-
001, should be conducted at the OLE Day 1 Visit (or repeated in the case that the assessment 
requires re-evaluation on the same day just prior to dosing [eg, pregnancy test]) in accordance 
with the Table of Events (Table 3).  Subjects will not be allowed to enroll in the OLE study 
and receive CC-93538 on OLE Day 1 if there will be a delay of > 21 days from CC-93538 
dosing in Study CC-93538-EE-001 or in Study CC-93538-DDI-001, unless discussed with the
Medical Monitor.

Guidance regarding baseline EGD and transition from the parent study follows:

For subjects transitioning from Study CC-93538-EE-001, the EGD procedure does not
need to be repeated at the OLE Day 1 Visit, as long as this assessment was conducted at 
the final Induction Phase (Week 24) or Maintenance Phase (Week 48) Visit.

For subjects transitioning from Study CC-93538-DDI-001, the EGD procedure does not 
need to be repeated at the OLE Day 1 Visit, as long as this assessment was conducted prior 
to the End of Treatment Visit.
If not available in the parent study as noted above, an EGD conducted at the OLE Day 1 
Visit will serve as the baseline for Study CC-93538-EE-002.

If subjects had an EGD performed for an EoE flare assessment during the Induction (prior 
to Week 24) or Maintenance (prior to Week 48) Phases in Study CC-93538-EE-001, an 
EGD will also be performed at Weeks 24 or 48, unless the EoE flare assessment occurred 
too close from the Week 24 or Week 48 Visits based on the Investigator’s judgement, such 
that it is considered unsafe to perform another EGD in such a short interval.  Discuss with 
the Medical Monitor well in advance of the OLE Day 1 Visit.  

For subjects transitioning from Study CC-93538-EE-001, if OLE Day 1 is not on the same day 
as the final Induction Phase (Week 24) or Maintenance Phase (Week 48) Visit in Study CC-
93538-EE-001, a urine (or serum) β-subunit of human chorionic gonadotropin (β-hCG) 
pregnancy test (females of child-bearing potential only) must be performed on OLE Day 1 and 
the results reviewed on OLE Day 1 prior to the first OLE CC-93538 dose. For subjects 
transitioning from Study CC-93538-DDI-001, if a pregnancy test was not completed on the 
same day as OLE Day 1, then a pregnancy test (urine or serum) must be performed on OLE 
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Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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Day 1 and the results reviewed prior to the first dose.  A negative pregnancy test result must 
be obtained for these subjects prior to dosing. If the urine pregnancy test result is positive but 
this is believed to be a false positive, the site may perform a serum pregnancy test at the local 
laboratory to confirm pregnancy status.
After eligibility has been confirmed and baseline assessments have been completed, eligible 
subjects will receive CC-93538 360 mg in an open-label manner. 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.  
Subsequent visits, assessments and procedures will be performed as shown in Table 3.
Following OLE Day 1, in the first year of the OLE study (OLE Treatment Period Year 1), subjects 
will attend study visits through Week 48.  After completion of Week 48 plus an additional 4 weeks 
in the OLE Treatment Period (that is, after Week 52 in the OLE study), subjects will continue on 
into the second year of the OLE (Year 2 and beyond).  During Year 2 and beyond, subjects will 
attend study visits every 13 weeks (±14 days) for a total of 4 quarterly study visits each year within 
a 52-week per year format. For each year of participation after Week 52, the Quarterly 1 Visit, 
Quarterly 2 Visit, Quarterly 3 Visit, and Quarterly 4 Visit will be completed.  The Quarterly 2 and 
4 Visits will include additional assessments not conducted in Quarterly 1 and 3 Visits.  The time
points for these visits are as follows:

Quarterly 1 Visits will occur at the end of the first quarter of each year after Week 52 (Year x 
+ Week 13 [± 14 days])

Quarterly 2 Visits will occur at the mid-point of each year after Week 52 (Year x + Week 26 
[± 14 days])

Quarterly 3 Visits will occur at the end of the third quarter of each year after Week 52 (Year x 
+ Week 39 [± 14 days])

Quarterly 4 Visits will occur at the end of each year after Week 52 (Year x + Week 52 [± 14 
days])
For example, for the Quarterly 1 Visit occurring at Week 13, where Year x is Year 2, the visit will 
occur at 52 Weeks plus 13 Weeks = Week 65, and for the Quarterly 4 Visit, where Year x is Year 
2, the visit will occur at 52 Weeks plus 52 Weeks = Week 104.
The following will be performed during the Open-label Extension Treatment Period as specified 
in the Table 3:

Prior therapy and concomitant therapy.  The use of concomitant medication and procedures 
will be monitored throughout the study. Refer to Section 8 for prohibited concomitant 
therapies.

Adverse event assessment begins when the subject signs the informed consent/assent form (in 
either parent study, Study CC-93538-EE-001 or Study CC-93538-DDI-001).  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. Ongoing AEs 
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Final: 30 Jun 2023
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first documented in Study CC-93538-EE-001 or Study CC-93538-DDI-001 will continue to be 
followed in the OLE study.  The timing of AE assessment documentation for the OLE study 
will begin at the time of or after the first dose in the OLE study (on OLE Day 1); AEs occurring 
before this timeframe will be documented in Study CC-93538-EE-001 or Study CC-93538-
DDI-001, respectively.  Refer to Section 10 for definitions of AEs/SAEs, monitoring, and 
reporting. In addition, AI/PFS device failures or malfunctions should be captured, and device 
related AEs should also be collected.

Hematology, chemistry, 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:  sodium, potassium, chloride, calcium, magnesium, phosphate, blood 
urea nitrogen, random glucose, albumin, alkaline phosphatase, creatinine, creatine 
phosphokinase (CPK), alanine aminotransferase/serum glutamic pyruvic transaminase 
(ALT/SGPT), aspartate aminotransferase/serum glutamic oxaloacetic transaminase 
(AST/SGOT), gamma glutamyltransferase (GGT), amylase, total bilirubin, direct bilirubin 
and C-reactive protein (CRP)

Urinalysis:  leukocytes, specific gravity, bilirubin, blood, glucose, ketones, pH, protein,
and urobilinogen

The hematology, chemistry, and urinalysis will be performed pre-dose (except for the 
ET/EoT Visit and 2 Safety Follow-up Visits) at the time points outlined in the Table of 
Events (Table 3).

Pregnancy test (only for FCBP):  A urine (or serum) pregnancy test for β-hCG will be 
performed at OLE Day 1/Baseline and urine pregnancy tests will be done at subsequent visits 
according to the Table of Events (Table 3).  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 each 
study visit, the Investigator will counsel FCBP subjects on pregnancy precautions for the 
duration of the study. A pregnancy test does not need to be repeated if it has been conducted 
at the final visit in Study CC-93538-EE-001 or Study CC-93538-DDI-001, and OLE Day 1
with dosing of CC-93538 occurs on the same day that the test was conducted and results 
reviewed.

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 (Table 3).  All significant findings that were present at 
screening in Study CC-93538-EE-001 or Study CC-93538-DDI-001 must be reported on the 
relevant medical history/current medical conditions eCRF. Significant findings made at the 
time of or after the first dose in the OLE study (on OLE Day 1) that meet the definition of an 
AE must be recorded in the OLE Study.  Note that ongoing AEs first documented in Study 
CC-93538-EE-001 or Study CC-93538-DDI-001 will be followed during the OLE study.
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Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
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
Height and weight:  Height will be measured in centimeters in all subjects for the OLE Day 1 
assessment but will only be required in adolescent subjects at subsequent time points; weight 
will be measured in kilograms in all subjects during the study.

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.  In 
case the cuff sizes available are not large enough for the subject’s arm circumference, a 
sphygmomanometer with an appropriately sized cuff may be used.

Serum antibodies to CC-93538 (Section 6.5)

Serum CC-93538 PK assessment (Section 6.6)

Circulating biomarkers assessment (Section 6.7.1)

SARS-CoV-2 serology assessment (Section 6.7.1)

Modified Daily Symptom Diary (mDSD) (Section 6.4.2.1)

Phone call reminder for mDSD completion (just prior to Week 22, Week 46, Week 100, and 
Week 102)

PGI-S (Section 6.4.2.2) 

CGI-S (Section 6.4.2.3)

GIC-EoE in subjects transitioning from Study CC-93538-EE-001 only (Section 6.4.2.4) 

EEsAI (Section 6.4.2.5) 

Pediatric Eosinophilic Esophagitis Symptom Severity Module (PEESS) in adolescents only
(Section 6.4.2.6)

Health-related quality of life (SF-12v2 in adults; 10-Item Short Form Health Survey for 
Children [SF-10] in adolescents) (Section 6.9)

WPAI:SHP in adults only (Section 6.9)

 
 
 
 
 

Health resource utilization will be monitored throughout the study and recorded at each study 
visit including but not limited to emergency department visits or hospitalizations for food 
impaction, procedures such as esophageal dilation, urgent care visits, health care provider 
office visits, or use of rescue therapy.

EGD with tissue biopsies:  Note that SARS-CoV-2 molecular testing through local laboratory 
assessment may be performed per standard of care and as required per institutional and local 
guidance prior to the EGD (Section 6.4.1) 

EREFS (Section 6.4.1)

Informed consent/assent for the optional EndoFLIP sub-study, if applicable

Optional EndoFLIP sub-study in subjects transitioning from Study CC-93538-EE-001 only 
(Section 6.11)

IP administration (refer to Section 7.2)
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Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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6.2.1
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 eCRF, if feasible, a sample should 
also be sent to the central laboratory.
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 sheets will be filed with the subject’s source documents. 
Reporting of laboratory AEs is described in Section 10.3.
In addition, for COVID-19 detection and prevention measures, SARS-CoV-2 molecular testing 
through local laboratory assessment may be performed per standard of care and as required per 
institutional and local guidance.
6.2.2
First Autoinjector Administration Visit
An additional First AI Administration Visit will be required for all subjects currently in the study 
whose next scheduled protocol visit is not within 4 weeks of Protocol Amendment 2 site approval
and once IP is available on site. 
The following evaluations will be performed as specified in Table 3:

Concomitant therapy

Assessment of AEs/SAEs

AI Administration Questionnaire (Section 6.9.2)

IP administration (Section 7.2)
6.2.3
EoE Flare Assessment Visit
Subjects with a worsening of EoE symptoms during the study will be required to complete the EoE 
Flare Assessment Visit as shown in the Table of Events (Table 3).  Subjects with increased signs 
and symptoms of EoE are instructed to contact the Investigator and/or study staff to determine if 
an EoE Flare Assessment Visit is warranted.  An EoE Flare Assessment Visit should be scheduled 
as close as possible to the time that an EoE flare is suspected.
Any worsening of EoE symptoms during study participation will be documented as an EoE flare.  
See Section 6.4.2.7 for the protocol definition of EoE flare and EoE Flare Assessment Visit details.
In the event that a subject discontinues the study due to an EoE flare, the ET/EoT Visit will also 
be completed, but procedures performed at the EoE Flare Assessment Visit do not need to be 
repeated for the ET/EoT Visit.
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The following evaluations will be performed as specified in Table 3:

Concomitant therapy

Assessment of AEs/SAEs

Hematology, chemistry, and urinalysis

Weight

Vital signs

PGI-S 

CGI-S

GIC-EoE

EEsAI

PEESS in adolescents only

Health resource utilization

EGD with tissue biopsies*

EREFS*
Refer to Section 6.4 for a description of the efficacy assessments conducted throughout the study.
6.2.4
Early Termination or End of Treatment Visit
For subjects who discontinue the study for any reason, the assessments detailed in the ET/EoT
Visit should be completed within 2 weeks after the final CC-93538 dose (Table 3). The ET Visit 
will be completed if discontinuation occurs before the Quarterly 4 Visit at the end of Year 2 (Week 
104); the EoT Visit will be completed if discontinuation occurs at or after the Quarterly 4 Visit at 
the end of Year 2 (Week 104).  If the EoT Visit occurs at the scheduled Quarterly 4 Visit at the 
end of Year 2 (Week 104), the subject will complete all assessments required for each of the 2
visits collectively (ie, assessments do not need to be repeated). In addition, these subjects should 
return for the Interim 8-week and Final 16-week Safety Follow-up Visits (Section 6.3.1).
The following evaluations will be performed as specified in the Table 3:

Concomitant therapy

Assessment of AEs

Hematology, chemistry, and urinalysis

Pregnancy test (only for FCBP)

Physical examination

Height (in adolescents only) and weight

Vital signs

Serum antibodies to CC-93538

Serum CC-93538 PK assessment
* Note that EGD is not required at EoE Flare Assessment Visits; if EGD is conducted, data should be collected 
when available, and if feasible, a sample may be collected and sent to the central reader for histologic analysis.
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Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
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
Circulating biomarkers assessment

SARS-CoV-2 serology assessment 

PGI-S 

CGI-S

GIC-EoE

EEsAI

PEESS in adolescents only

SF-12v2 in adults and SF-10 in adolescents

WPAI:SHP in adults only

Health resource utilization

EGD with tissue biopsies*

EREFS*

Adverse event evaluation (monitored through 16 weeks after the last dose of IP)
6.3
Follow-up Period
6.3.1
Safety Follow-up Visits (Interim 8-week and Final 16-week)
All subjects will be followed for 16 weeks after the last dose of CC-93538 for AE reporting, as 
well as SAEs made known to the Investigator at any time thereafter that are suspected of being 
related to CC-93538, as described in Section 10.2.3. All subjects should return at both 8 weeks 
and 16 weeks (± 7 days) after their last dose of CC-93538 to complete the Interim 8-week and 
Final 16-week Safety Follow-Up Visits and assessments shown in Table 3.
6.4
Efficacy Assessment
6.4.1
Esophagogastroduodenoscopy (EGD)
To ensure quality data and standardization, the same person should perform endoscopic procedures 
at a study site at each study visit. 
The EGD biopsy results for eosinophil counts will be read at a centralized reading facility, and 
sites will send the biopsy specimens to the centralized reading facility.
For the OLE Day 
1/Baseline EGD only (ie, the EGD conducted in Study CC-93538-EE-001 at either the Week 24 
Visit or Week 48 Visit), biopsy results will be read blinded to treatment allocation and results will 
be blinded to investigative sites.  A local histologic assessment of EGD biopsy samples should not 
be performed, unless required for safety reasons (eg, severe EoE flare, AEs, or incidental findings, 
etc).  Any incidental findings of potential clinical relevance that are not directly associated with 
the objectives of the study should be evaluated and handled by the Investigator per the site’s
standard of care and clinical judgment.  More detailed instructions for specimen collection, 
processing, storage, and shipping will be provided in a separate Biopsy Quick Reference Card and 
a Study Laboratory Manual.
* The EGD will be completed at the ET Visit if the visit occurs before or at Week 48 but is not required if within 8 
weeks since the last EGD.  The EGD is not required at ET Visits after Week 48.
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Celgene International II Sàrl
CC-93538-EE-002 Amendment 2
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Endoscopic procedures will be performed as follows:

EGD will be performed at the time points specified in the Table of Events (Table 3).  Note that 
SARS-CoV-2 molecular testing through local laboratory assessment may be performed per 
standard of care and as required per institutional and local guidance prior to the EGD.  

Biopsies should be obtained from 3 levels, the proximal, mid, and distal esophagus as follows:

Distal esophagus (3 to 5 cm above the Z-line [squamo-columnar junction])

Proximal esophagus (≈15 cm above the Z-line and within 10 cm of the esophageal inlet)

Mid esophagus (approximately mid-way between the proximal and distal biopsies)

All subsequent biopsies should be obtained from the same levels as the screening biopsies in 
Study CC-93538-EE-001 or Study CC-93538-DDI-001 (ie, all 3 levels) maintaining 
consistency throughout the study.

Biopsy samples must be obtained from 2 to 4 separate areas at each level, ideally from the 
areas with the most prominent visible abnormalities. For example, if 2-bite biopsies are being 
obtained, a minimum total of 4 biopsy fragments (from 2 separate 2-bite biopsies) would be 
obtained from each esophageal level.

Histologic analysis of the esophageal biopsy samples for any study-specific assessments will 
be performed by a central laboratory including enumeration of eosinophil count (peak 
eosinophil count) by analysis of hematoxylin and eosin (H&E) stained biopsies and EoE 
histology scoring system (EoEHSS) assessment (histology grade and stage score).

Endoscopic findings including but not limited to the 5 classification categories will be assessed 
by each Investigator using the EREFS (Hirano, 2013) at the time points specified in the Table 
of Events (Table 3).  The classification features include edema, fixed rings, exudates, furrows, 
and stricture. Assessments will be conducted at all 3 levels of the esophagus (the proximal, 
mid, and distal).

In addition to obtaining the eosinophil counts required for exploratory endpoint determination, 
the esophageal biopsies will be used for evaluation of potential diagnostic and 
pharmacodynamic 
markers 
using 
appropriate 
laboratory 
methodology, 
including 
histopathology, immunohistochemistry, and transcript profiling.
6.4.2
Clinical Symptoms of EoE
6.4.2.1
Modified Daily Symptom Diary (mDSD)
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6.4.2.2
Patient Global Impression of Severity (PGI-S)
The PGI-S is a single-item assessment of disease severity where subjects are asked, “Please rate 
the severity of your EoE symptoms over the past 2 weeks.” A 5-point verbal response scale is 
used, including “None,” “Mild,” “Moderate,” “Severe,” and “Very severe.” 
The PGI-S will be assessed via an eDiary according to the time points detailed in the Table of 
Events (Table 3).
6.4.2.3
Clinician Global Impression of Severity (CGI-S)
The CGI-S is a single-item assessment of disease severity where clinicians are asked, “Please rate 
the severity of the patient’s EoE symptoms over the past 2 weeks.” A 5-point verbal response 
scale is used, including “None,” “Mild,” “Moderate,” “Severe,” and “Very severe.”
The CGI-S will be completed by clinicians via paper or electronic methods.  The CGI-S will be 
assessed as specified in Table 3.  Whenever possible, the same assessor should perform the CGI-S 
for all time points for a given subject.
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CC-93538-EE-002 Amendment 2
Final: 30 Jun 2023
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6.4.2.4
Global Impression of Change in EoE Symptoms (GIC-EoE)
In the OLE study, the GIC-EoE is a single-item assessment where subjects are asked, “Since you 
completed your participation in Study CC-93538-EE-001, how would you describe the change in 
your EoE symptoms?” Response options include “A lot better”, “A little bit better”, “Stayed the 
same”, “A little worse”, and “Much Worse”.  Only subjects transitioning from Study CC-93538-
EE-001 will complete the GIC-EoE.
The GIC-EoE will be assessed via an eDiary at time points outlined in Table 3.
6.4.2.5
Eosinophilic Esophagitis Symptom and Activity Index (EEsAI)
The EEsAI was developed in the English language as a paper-based patient-reported outcome 
(PRO) with a 7-day recall period and takes less than 10 minutes to complete (Schoepfer, 2014b). 
For the CC-93538 Phase 3 studies, only the 10-item symptoms (dependent on eating and drinking) 
domain will be included.
The EEsAI includes the visual dysphagia question (VDQ) which addresses the severity of 
dysphagia when consuming food of 8 distinct consistencies. The 8 food consistencies and 
examples of foods to illustrate those consistencies are as follows: (1) solid meat (such as steak, 
chicken, turkey, and lamb), (2) soft foods (such as pudding, jelly, and apple sauce), (3) dry rice or 
sticky Asian rice, (4) ground meat (hamburger and meatloaf), (5) fresh white untoasted bread or 
similar foods (such as doughnuts, muffins, and cake), (6) grits, porridge (oatmeal), or rice pudding, 
(7) raw fibrous foods (such as apples, carrots, and celery), and (8) French fries (Schoepfer, 2014b). 
Each VDQ food consistency is answered with a Likert-like scale ranging from “no difficulties” to 
“severe difficulties.” Further, the behavioral adaptations of avoidance, modification, and slow 
eating (AMS) are assessed for the same 8 food consistencies. The AMS section contains 4 yes/no 
questions for each of the 8 food consistencies.  Additionally, the questionnaire includes items 
assessing the frequency and duration of trouble swallowing and pain associated with swallowing.  
The EEsAI total score ranges from 0 to 100, with a high score indicating more dysphagia 
symptoms and behavioral adaptations. A score from 0 to 20 has been previously defined as clinical 
remission (Safroneeva, 2015a; Safroneeva, 2015b).
The EEsAI will be assessed at time points outlined in Table 3.
6.4.2.6
Pediatric Eosinophilic Esophagitis Symptom Severity Module (PEESS)
The Pediatric Eosinophilic Esophagitis Symptom Severity Module, version 2.0 (PEESS v2.0) is a 
validated instrument that assesses symptoms of EoE in children and adolescents aged 2 to 18 years 
(Franciosi, 2011).  A parent proxy report for children and teenage children ages 2 to 18 and a 
children and teen report for ages 8 to 18 are available; the children and teen report will be used for 
this study and will be assessed in adolescent subjects only. The module assesses the frequency 
and severity (depicted with ideograms) of symptoms in the past month with each item on a scale 
of 0 to 4 (4 being the highest level of frequency/severity).  Scores for each item are transformed to 
a 0 to 100 point scale and the total metric score will be computed as the mean of the item scores.
The PEESS will be assessed at time points according to Table 3.
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CC-93538-EE-002 Amendment 2
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6.4.2.7
Worsening of EoE Symptoms, EoE Flare, the EoE Flare Assessment 
Visit, and Lack of Improvement
Subjects with a worsening of EoE symptoms during the study will be required to complete the EoE 
Flare Assessment Visit as shown in the Table of Events (Table 3).  Subjects with increased signs 
and symptoms of EoE are instructed to contact the Investigator and/or study staff to determine if 
an EoE Flare Assessment Visit is warranted, which should be scheduled as close as possible to the 
time that an EoE flare is suspected.
An EoE Flare Assessment Visit including safety and efficacy evaluations can occur at any time 
during the study.  While EGD is not required, if an endoscopy is conducted as an intervention for 
a subject with a worsening of symptoms or flare, details of the endoscopic procedure should be 
collected when available, and if feasible, a sample may be collected and sent to the central reader.  
The Investigator will confirm if the worsening of EoE symptoms requires rescue therapy and, thus, 
is deemed a severe EoE flare according to the following protocol definitions.  
Any worsening of EoE symptoms during study participation will be documented as an EoE flare. 

A severe EoE flare is defined as any worsening of EoE symptoms including a high intensity 
episode resulting in emergency department visit or hospitalization, with the need for 
endoscopic intervention (eg, for prolonged food impaction) and/or need for rescue therapy (eg, 
including but not limited to corticosteroid therapy or dilation), or a worsening of EoE 
symptoms resulting in the need for rescue therapy only without endoscopic intervention.  

A mild to moderate EoE flare is defined as any worsening of EoE symptoms without the need 
for rescue therapy or endoscopic intervention.
During the course of the study, subjects who demonstrate a persistent lack of improvement or 
worsening of EoE symptoms should be evaluated to determine if continuing the study treatment is 
appropriate.  While subjects will have the opportunity to continue participation in the OLE with 
use of rescue therapy as needed, based on clinical judgment, the Investigator should discontinue 
any subject in which study participation no longer is in the best interest of the subject.  
Subjects who are discontinued from the OLE study will be asked to complete an ET/EoT Visit 
(Section 6.2.4) and the 2 Safety Follow-up Visits (Section 6.3.1).  The ET/EoT Visit procedures 
performed at the EoE Flare Assessment Visit do not need to be repeated for subjects who 
discontinue the study due to an EoE flare.
6.5
Anti-drug Antibody Assessments
Serum samples to assess blood levels of antibodies to CC-93538 will be obtained pre-dose (except 
for the ET/EoT Visit and 2 Safety Follow-up Visits) at the time points outlined in the Table of 
Events (Table 3).
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 anti-CC-93538 antibodies will be monitored to assess the impact of 
immunogenicity on safety, PK, and efficacy of CC-93538. The impact of immunogenicity will be 
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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.
6.6
Pharmacokinetics 
6.6.1
Serum CC-93538 Assessments
Serum samples to assess CC-93538 concentrations will be obtained pre-dose (except for the 
Termination and 2 Safety Follow-up Visits) at the time points described in the Table of Events 
(Table 3).  In the event that dosing occurs during a non-clinic visit day, it is still acceptable to 
obtain the serum samples. CC-93538 concentration data will be used for population PK analysis 
and determination of exposure-response and pharmacodynamic relationships as described in 
Section 9.9.1.
Details of the procedures to be followed for sample collection, processing, storage, shipment, and 
testing will be documented in a separate Study Laboratory Manual.
6.7
Biomarkers, Pharmacodynamics, Pharmacogenomics
6.7.1
Circulating Biomarker Assessments
Blood samples will be obtained pre-dose (except for the ET/EoT Visit and 2 Safety Follow-up 
Visits) to evaluate levels of various circulating biomarkers including, but not limited to, periostin, 
eotaxin-3, IL-13, and possible assessments of SARS-CoV-2 serologic status according to the Table 
of Events (Table 3).  Data obtained from the pharmacogenomic sample (eg, IL-13 single nucleotide 
polymorphism [SNP] characterization) collected in Study CC-93538-EE-001 will be included in 
the biomarker endpoint analysis for this study.  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, in addition to the scheduled time points listed in Table 3, serum will also be collected for 
SARS-CoV-2 serology approximately 4 weeks after a documented or suspected SARS-CoV-2 
infection.
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.
6.7.2
Tissue Biomarker Assessments
Tissue biomarkers will be evaluated using tissue obtained from the study-specified esophageal 
biopsies when possible at time points detailed in Table 3. Sample collection and processing will 
be described in a separate Study Laboratory Manual.  Biomarkers that will be evaluated are thought 
to play a role in EoE disease pathogenesis and may have diagnostic or prognostic importance; 
methodologies such as immunohistochemistry and transcriptome analysis may be employed.  
These biomarkers include but are not limited to markers of epithelial mesenchymal transition 
(EMT), eotaxin-3, and periostin. These biomarker assessments will be performed at a central 
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laboratory and other specialized laboratories.  Esophageal tissue biomarkers will not be assessed 
in subjects transitioning from Study CC-93538-DDI-001.
6.8
Additional and Optional Research
Additional and optional research (requiring subject consent/assent) 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.
6.8.1
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.
6.8.2
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.
6.9
Subject-Reported Outcomes
6.9.1
Health-related Quality of Life
The 12-Item Short Form Health Survey (SF-12v2; Ware, 1996) and the 10-Item Short Form Health 
Survey for Children (SF-10; Saris-Baglama, 2007) will be used to measure health-related quality 
of life (HRQoL).  Adult subjects will be administered the SF-12v2 while adolescent subjects will 
be given the SF-10 Survey.  The SF-12v2 contains 12 questions and measures 8 domains including 
physical and mental aspects of health.  The SF-10 contains 10 questions and is completed by the 
parent.
The Work Productivity and Activity Impairment Questionnaire (WPAI) measures work 
productivity and the ability to perform activities (Reilly, 1993).  The WPAI: Specific Health 
Problem V2.0 (WPAI:SHP) adapted for this study includes 6 questions that assess the impact of 
the subject’s EoE symptoms on work productivity and other activities.  As such, the assessment 
utilized in this study is also designated as Work Productivity and Activity Impairment 
Questionnaire: Eosinophilic Esophagitis (WPAI:EE).  The questionnaire will be administered to 
adult subjects only. 
Subjects will complete these instruments according to Table of Events as detailed in Table 3. 
6.9.2
Autoinjector (AI) Administration Questionnaire/PFS Administration 
Questionnaire
The CC-93538 AI was developed to enable a safe, effective, consistent, and convenient SC 
administration of IP by subjects in an at home environment, in addition to administration in the 
clinic. For study conduct under Protocol Amendment 1 (dated 10 May 2022), the PFS 
Administration Questionnaire was employed to evaluate the success of self-administration of 
CC-93538 by the 
PFS presentation; with the implementation of Protocol
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Amendment 2, only the AI Questionnaire will be employed going forward. The purpose of the 
AI/PFS Administration Questionnaire is to evaluate the success of self-administration of CC-
93538 by the AI/PFS during actual use under both supervised (in-clinic) and unsupervised (at
home) conditions during the study. 
 
 
 
   
6.10
Health Resource Utilization
Health resource utilization will be evaluated during the OLE study as indicated in the Table of 
Events (Table 3) through documentation of complications of EoE including but not limited to
emergency department visits or hospitalizations for food impaction, procedures such as esophageal 
dilation, urgent care visits, and health care provider office visits, or use of rescue therapy.  After 
study discontinuation or completion, subjects may be contacted for follow-up health resource 
utilization information.
6.11
Endolumenal Functional Lumen Imaging Probe (EndoFLIPTM) Sub-study
An optional sub-study will be performed at a subset of clinical sites utilizing an EndoFLIP to 
evaluate the effects of CC-93538 on esophageal distensibility. 
The EndoFLIP assessment 
evaluates esophageal function and is a tool that will complement histologic, endoscopic, and 
symptomatic findings. An EndoFLIP will be placed into the esophagus transorally during EGD
and positioned with recording sites covering a 16 cm span of the proximal to distal esophagus. 
Cross sectional areas within the esophagus and intrabag pressure will be measured.  
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The EndoFLIP procedure is an optional assessment.  Only subjects transitioning from Study CC-
93538-EE-001 and who have participated in the sub-study during enrollment in Study CC-93538-
EE-001 are eligible to participate in this assessment for Study CC-93538-EE-002.  For sites who 
participate and subjects who consent to participation in the EndoFLIP sub-study, this procedure 
should be performed at the time of the scheduled EGD at visits indicated per the Table of Events 
in Table 3. Please refer to the EndoFLIP™Procedure Manual for complete information on 
EndoFLIP procedure instructions and required equipment and supplies.
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7
DESCRIPTION OF STUDY TREATMENTS
7.1
Description of Investigational Product(s)
The active ingredient of CC-93538 is a recombinant humanized IgG1 monoclonal antibody 
directed against human IL-13. Investigational product (CC-93538) is to be stored at 
 to 
C. 
The IP should not be 
. The labeling will be in accordance with GCP and any other local 
regulatory requirements. During the study, IP will be dispensed in an AI presentation provided by 
the Sponsor. The 360 mg dose of CC-93538 will be administered by a 
at 
a concentration of 
mg/mL.
Specific handling and dispensing instructions are provided below.
IP in AI
An AI presentation containing CC-93538 drug product at a concentration of 
 mg/mL in a 
 
fill (for a total of 
) will be utilized in this study.  The CC-93538 360 mg in an AI is 
a single use, disposable, ready-to-use SC combination product consisting of CC-93538 injection 
in the bulk-filled syringe integrated into a functional AI device. No additional drug preparation is 
required prior to administration. CC-93538 solution for injection will be provided as a sterile 
liquid in an AI at a concentration of 
 mg/mL packaged in cartons (one AI per carton). At home 
self-administration (as outlined in Section 7.2.1) or administration of IP through a home health 
nurse (as outlined in Section 7.2) will be available IP administration options with the AI.
Additional instructions related to IP handling, preparation, and dispensation will be provided in a 
separate Study Pharmacy Manual (including an Instructions for Use document).
7.2
Treatment Administration and Schedule
The dosing schedule in the OLE study is as follows:

CC-93538 360 mg SC once weekly during the OLE treatment Period
All subjects in the OLE study will receive CC-93538 360 mg SC once weekly during the OLE 
Treatment Period. The dosing regimen for the OLE may be revised, via an amendment to the 
protocol, after results from the core Induction and Maintenance Study, CC-93538-EE-001, are 
available and the optimal dosing regimen is confirmed.  
On OLE Day 1, eligible subjects will be administered CC-93538 (360 mg) as a 
 
CC-93538 SC injection. Subjects will receive 
 CC-93538 SC injection once weekly 
throughout their participation in the OLE study (
 at 
 mg/mL CC-93538 = 360 mg CC-
93538/week).
The original protocol required CC-93538 weekly SC dosing to be administered by 
 
 of 
 mL each at a concentration of 
 mg/mL (for a total dose of 360 mg SC once
weekly).  Protocol Amendment 1 (dated 10 May 2022) required CC-93538 weekly SC to be 
administered using a PFS by a 
 at a concentration of 
mg/mL (for a 
total dose of 360 mg SC once weekly). 
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All subjects currently in the study and any new subjects entering the study will start receiving a 
 of the
 AI once the second amendment to the protocol (Protocol 
Amendment 2) is implemented, informed consent is obtained, and IP is available at the site. For 
currently enrolled subjects who did not begin the study with the new AI presentation, a switch to 
the new AI presentation will occur at the next regularly scheduled study visit.  However, a First
AI Administration Visit will be required for subjects whose next scheduled protocol visit is not 
within 4 weeks of Protocol Amendment 2 site approval and IP is available on site to expedite 
presentation switch from PFS to AI. The visit may be scheduled at any time within this 4-week 
period.
During the study, weekly SC doses should be administered on the same day each week at 
approximately the same time of day.  As the OLE will include subjects previously treated with 
placebo, to ensure safety, and to preserve the maintenance of the blind from Study CC-93538-EE-
001, the first 3 weekly SC doses will be required to be administered in the clinic for all subjects
entering OLE.  Subjects will remain in the clinic for at least 30 minutes following dosing for 
observation. The number of injections to be administered in the clinic and/or the post injection 
observation time may be extended per Investigator discretion or to comply with local requirements.  
To ensure accurate dose administration and compliance with the new 
 weekly SC 
injection using the 
 AI presentation, for subjects who did not begin the study with 
this new presentation (on OLE Day 1), one additional in-clinic weekly dose with at least a 30-
minute observation is required for the first administration.  This first dose will occur either at the 
time of the subject’s next scheduled protocol required study visit or the First AI Administration 
Visit as described in Table 3. Further, subjects will complete the AI Administration Questionnaire 
at the time of this first in-clinic dose. 
In the event the IP (AI) is not available on-site at the time of Protocol Amendment 2 site approval, 
subjects should continue receiving the 
 weekly SC injection using the 
PFS presentation until the IP (AI) is available. Subjects who self-administer (as defined in 
Section 7.2.1) with the PFS presentation should continue to complete the PFS Administration 
Questionnaire until the switch to the new AI presentation occurs. 
The SC doses should be administered as described in the Instructions for Use document, avoiding 
any blood vessels, thickened or tender skin, scars, fibrous tissue, stretch marks, bruises, redness, 
nevi, or other skin imperfections. Refer to the Pharmacy Manual and Instructions for Use for 
additional specifications regarding administration, including guidance regarding anatomical 
locations for injection and rotation of the injection site.
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. 
Doses of CC-93538 that do not align with required study visits may be administered either in the 
clinic by study personnel or at the subject’s home through self or caregiver administration or by a 
visiting home health nurse (once the subject has completed the first 3 required in-clinic doses).
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7.2.1
Self-Administration
Self-administration (defined as either by subject or by caregiver, applicable per local regulations) 
will be an option for dose administration of CC-93538 by the AI presentation.  For subjects 
enrolled in Japan, self-administration should be performed by the subject himself/herself in 
principle; however, in the event that it is not feasible for the subject to self-administer CC-93538, 
self-administration may be performed by a family member.  Subjects will be provided with an 
Instructions for Use document outlining steps for proper dose administration.
Self-administration will be dependent on the subject’s (or caregiver’s) ability to perform dose 
administration and is independent of the subject’s age. To ensure the subject’s suitability for self-
administration, the Investigator and site staff will evaluate each subject for adherence to protocol 
requirements and must feel comfortable that the subject is willing to comply with the 
 regimen no matter how well the subject may feel during the study.  Subjects who self-
administered IP in Study CC-93538-EE-001 or Study CC-93538-DDI-001 should continue this 
practice in the OLE.  Subjects who initiate self-administration in the OLE will be required to 
perform, at a minimum the first 3 weekly injections on-site in the presence of site personnel.  The 
number of on-site injections may be increased based on Investigator judgment or other local 
requirements.  This will allow for on-site training and a skill assessment to be done by the site 
personnel to ensure the subject (or subject’s caregiver) is proficient with self-injection.  In addition, 
continued injection compliance checks will occur during the course of the study, when the subject 
doses on-site at the scheduled study visits.  As subjects transition from the parent study to the OLE 
study, subjects will be allowed to switch their method of administration (eg, from in-clinic or home 
health nurse service to self-administration) based on Investigator judgment if it is in the best 
interest of the subject, the subject demonstrates proficiency, and a change is not anticipated to 
impact compliance. To help promote consistency within the data, it is preferred that subjects do 
not switch their injection method during the conduct of the OLE study, unless there is a reasonable 
rationale for doing so (eg, change in injection proficiency, treatment compliance issue, etc) per the 
clinical judgment of the Investigator.  For subjects who have difficulty self-administering IP, all 
weekly dosing will need to be conducted on-site or may be coordinated through a visiting home 
nurse (where locally feasible) to administer the IP to the subject during the OLE study.
7.2.2
Missed Dose(s)
If a subject is unable to take a dose of CC-93538 on the usually scheduled day:

The subject may take the dose within ±3 days of the normal dosing day and then continue 
dosing on the regular day the next week 

If the dose cannot be taken within ±3 days of the normal dosing day, the subject should wait 
to take the next dose on the regular dosing day the following week
, and Section 7.2.5 for criteria for 
discontinuation of dosing.
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7.2.3
Dose Adjustments
There is no provision for dose adjustments in this study. Subjects who cannot tolerate their 
assigned dose of CC-93538, as determined by the Investigator, will be permanently discontinued 
from IP (see Section 11.1).
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7.2.5
Criteria for Discontinuation of Dosing
Dosing will be permanently discontinued (treatment discontinuation) for a subject if the subject 
experiences any of the events listed in Section 11.1 following initiation of CC-93538.  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.  Subjects that discontinue the study will 
be asked to complete the ET/EoT Visit and the Interim 8-week and Final 16-week Safety Follow-
up Visits.
7.2.6
Rescue Therapy
During the study, subjects with a worsening of EoE symptoms requiring rescue therapy may 
continue study participation with concomitant therapy as described in Section 8.1.1.
7.3
Method of Treatment Assignment
Prospective subjects must provide proper informed consent/assent before any study procedures are 
performed (refer to Section 12.3 for further details regarding obtaining subject’s informed 
consent/assent). After all OLE baseline assessments have been completed and the Investigator has 
confirmed continued eligibility of the subject per the inclusion (Section 4.2) and exclusion criteria 
(Section 4.3), all eligible subjects will be assigned to the same IP and will receive open-label 
CC-93538 360 mg SC starting on OLE Day 1 and once weekly throughout the OLE study.
7.4
Packaging and Labeling
The label(s) for IP will include Sponsor name, address and telephone number, the protocol number, 
IP name, dosage form and strength (where applicable), amount of IP per container, lot number, 
expiry date (where applicable), medication identification/kit number, dosing instructions, storage
conditions, and required caution statements and/or regulatory statements as applicable. Additional 
information may be included on the label as applicable per local regulations.
7.5
Investigational Product Accountability and Disposal 
Celgene (or designee) will review with the Investigator and relevant site personnel the process for 
IP return, disposal, and/or destruction including responsibilities for the site versus Celgene (or 
designee).
All supplies of IP will be accounted for in accordance with GCP. There will be an individual IP 
accountability record for each subject and the Investigator should maintain accurate records 
relating to IP supplies received during the study. These records should include the amount of and 
dates clinical drug supplies were received, dispensed, and administered to the subject by the 
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investigative site or by a home healthcare nurse, or returned by the designated investigative site 
staff or by a home healthcare nurse and returned to the Sponsor. If errors or damages in the clinical 
drug supply shipments occur, the Investigator should contact the IP supplier and the Study Monitor 
immediately. Copies of the IP accountability records will be provided by each Investigator for 
inclusion in the Trial Master File after database lock. The Study Monitor will periodically check 
the supplies of IP held by the Investigator or pharmacist to verify accountability of all IP used.
The Investigator will provide IP only to the identified subjects of this study, according to the 
procedures described in this study protocol. After the end of the study, the Study Monitor will 
ensure that all unused IP and all medication containers, as applicable, can be destroyed on-site as 
long as proper documentation is supplied. If destruction on-site is not possible then any unused 
medication and containers, as applicable, will be returned to the Sponsor or designee. The Study 
Monitor will perform final accountability, package, seal and prepare for shipment.  The clinical 
research organization (CRO) will verify that a final report of drug accountability is prepared and 
maintained in the Investigator Trial Master File.
7.6
Investigational Product Compliance
The Investigator must ensure that the IP will be used only in accordance with the protocol and that 
subjects are correctly instructed on how to take their IP and that each subject is fully compliant 
with their assigned dosage regimen. Investigational product non-compliance is defined as taking 
less than 80% or more than 120% of IP doses during the study.  Records 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, vaccines, and procedures) used by subjects within the 4 weeks 
(28 days) prior to OLE Day 1/Baseline and at any time during the study in addition to the IP are 
regarded as prior or concomitant treatments and must be documented on the appropriate section of 
the eCRF; if the treatment started and stopped prior to the first dose on OLE Day 1, documentation
is only required on the parent study eCRF. A history of previous treatments for EoE used prior to 
participation in the core Induction and Maintenance Study, CC-93538-EE-001, or the Phase 1 
Study, CC-93538-DDI-001, will be documented as part of Study CC-93538-EE-001 or Study CC-
93538-DDI-001, respectively. 
All concomitant treatments, including blood and blood products, used from 28 days prior OLE 
Day1/Baseline until 16 weeks after the last dose of IP (ie, until the Final 16-week Safety Follow-
up Visit), must be reported on the eCRF. Treatment that started prior to the time of the first dose 
on OLE Day 1 will be documented in the parent study only, unless the use of such treatment is 
ongoing at or after the time of the first dose on OLE Day 1.  All treatments ongoing or started at 
the time of or after the first dose on OLE Day 1 will be documented in the CC-93538-EE-002 
eCRF.
8.1
Permitted Concomitant Medications and Procedures
Administration of non-live vaccines including COVID-19 vaccine (except for investigational 
COVID-19 vaccines administered as part of a clinical trial) is allowed and may occur during the 
study.  For COVID-19 vaccine regimens requiring more than one dose, the full series (eg, both 
doses of a 2-dose series) should be completed prior to enrollment in the parent study when feasible, 
and when a delay in enrollment would not put the study participant at risk.  Ideally, adverse events 
attributable to a vaccine should have resolved prior to enrollment.
8.1.1
Rescue Therapy
Prior to entry into the OLE study or during OLE study participation, subjects with a worsening of 
EoE symptoms requiring rescue therapy (defined as a severe EoE flare; refer to Section 6.4.2.7) 
may continue to participate in the study with concomitant rescue therapy.  Rescue therapy includes 
EoE standard of care pharmacotherapy (including but not limited to corticosteroids), dietary 
modification (eg, food elimination diet), and/or dilation procedure.  
8.2
Prohibited Concomitant Medications and Procedures
Concomitant medications and procedures that are prohibited in the Induction and Maintenance 
Study, CC-93538-EE-001, and the Phase 1 Study, CC-93538-DDI-001, and for the duration of the 
OLE Study, CC-93538-EE-002, (until the Final 16-week Safety Follow-up Visit) include:

Subjects may not use systemic immunosuppressive or immunomodulating drugs (including 
but not limited to, Janus kinase [JAK] inhibitors, phosphodiesterase-4 [PDE-4] inhibitors, anti-
IL-13 antibodies other than IP in this study, IL-4 receptor alpha antagonist, anti-IL-5 
antibodies, anti-IL-17 antibodies, anti-IgE antibodies, α4β7 integrin inhibitor antibodies, or 
any other monoclonal antibodies, methotrexate, cyclosporine, azathioprine, mercaptopurine, 
interferon alpha [IFNα], tumor necrosis factor alpha [TNFα] inhibitors, etc.) for at least 5 drug 
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half-lives prior to the first Screening Visit in Study CC-93538-EE-001 or Study CC-93538-
DDI-001 and through the duration of the OLE study.  Use of any of the aforementioned 
medications during study participation will result in the subject’s permanent discontinuation 
from IP.

Subjects may not receive oral or sublingual immunotherapy from the first Screening Visit in 
Study CC-93538-EE-001 and through the end of the OLE study. Subjects should not have 
received oral or sublingual immunotherapy within 6 months prior to the first Screening Visit
in Study CC-93538-EE-001 or Study CC-93538-DDI-001.

Subjects must not have received a live attenuated vaccine within 1 month of the first Screening 
Visit in Study CC-93538-EE-001 or Study CC-93538-DDI-001 through the end of the OLE 
study.

Concurrent treatment with another IP, including an investigational treatment or investigational 
vaccine for COVID-19, is not allowed. 
Prospective subjects may not participate in a 
concurrent IP study or have received an IP within 5 drug half-lives prior to the first Screening 
Visit in Study CC-93538-EE-001 or within 30 days or 5 drug half-lives (whichever is longer) 
prior to the first Screening Visit in Study CC-93538-DDI-001 and through the end of the OLE 
study.  Subjects who received an investigational COVID-19 vaccine as part of a clinical trial 
during the course of Study CC-93538-EE-001 will not be eligible to participate unless it is 
determined by discussion between the Investigator and the Clinical Trial Physician that the 
biologic impact of the vaccine is stabilized.
8.3
Required Concomitant Medications and Procedures
See Section 6.4.1 for EGD requirements.
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9
STATISTICAL CONSIDERATIONS
9.1
Overview
The OLE study is a Phase 3, open-label, uncontrolled study to explore the long-term effects of 
treatment with CC-93538 360 mg SC once weekly in adult and adolescent subjects with EoE who 
had previously participated in the Induction and Maintenance Study, CC-93538-EE-001, or Study 
CC-93538-DDI-001.  An independent Data Monitoring Committee (DMC) will be implemented
to review the safety data regularly during the course of the study.
All efficacy and safety data will be listed by subject.  Descriptive statistics will consist of the 
number of subjects (n), mean, standard deviation (SD), median, minimum, and maximum for 
continuous variables and counts and percentages for categorical variables.
For the OLE, all endpoints will be summarized using descriptive statistics and no hypothesis 
testing will be performed.  Comparisons between the different parent studies or cohorts will not 
be conducted.
All analyses including summaries and listings will be performed using SAS® software version 9.4
or higher.
9.2
Study Population Definitions
All study populations will be defined and documented prior to database lock. The following 
analysis populations will be used in the statistical analysis:
Analysis Population
OLE Population
The analysis population that will be used in the statistical analysis is the OLE population which 
consists of all subjects receiving at least one dose of IP during OLE.
The OLE population consists of subjects who were originally randomized to the 3 arms in Study 
CC-93538-EE-001 as well as subjects who participated in the parent Study CC-93538-DDI-001.
For subjects transitioning from Study CC-93538-EE-001, the 3 arms in the parent study were: 
placebo in both the Induction Phase and the Maintenance Phase, CC-93538 360 mg SC once 
weekly in the Induction Phase and CC-93538 360 mg SC once every other week in the 
Maintenance Phase, and CC-93538 360 mg SC once weekly in both the Induction Phase and the 
Maintenance Phase. These subjects can enter the OLE either: after completing Week 24 of the 
Induction Phase or after completing Week 48 of the Maintenance Phase. 
Subjects will be analyzed based on the treatments received during the core Induction and
Maintenance Study, CC-93538-EE-001, defined as:

For subjects who enter OLE after completing Week 24 of the Induction Phase, based on the 
treatment(s) the subjects received in CC-93538-EE-001 before they enter OLE, there are 2
different cohorts: 

Cohort A:
Subjects receiving placebo in the Induction Phase but did not enter the 
Maintenance Phase (denoted as “PBO/-”)
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
Cohort B:  Subjects receiving CC-93538 360 mg SC once weekly in the Induction Phase 
but did not enter the Maintenance Phase (denoted as “360 mg QW/-”)

For subjects who enter after completing Week 48 of the Maintenance Phase, based on the 
treatment(s) the subjects received in CC-93538-EE-001 before they entered OLE, there are 3
different cohorts:

Cohort C: Subjects receiving placebo in both the Induction Phase and the Maintenance 
Phase (denoted as “PBO/PBO”)

Cohort D: Subjects receiving CC-93538 360 mg SC once weekly in the Induction Phase 
and CC-93538 360 mg SC once every other week in the Maintenance Phase (denoted as 
“360 mg QW/360 mg Q2W”)

Cohort E: Subjects receiving CC-93538 360 mg SC once weekly in both the Induction 
Phase and the Maintenance Phase (denoted as “360 mg QW/360 mg QW”)
For subjects transitioning from Study CC-93538-DDI-001, their data will be summarized
separately. 
9.3
Sample Size and Power Considerations
As this is an OLE study for subjects who participated in the prior Study CC-93538-EE-001 or 
Study CC-93538-DDI-001, there is no statistical basis for the sample size. This is a descriptive 
study and comparisons between the parent studies or cohorts are not appropriate. It is anticipated 
that approximately 259 subjects who participated in Study CC-93538-EE-001 will be eligible for 
treatment in this study assuming an overall drop-out rate of 35% in Study CC-93538-EE-001 and 
approximately 
 subjects who participated in Study CC-93538-DDI-001 will be eligible for 
treatment in this study.  
9.4
Background and Demographic Characteristics
Subject demographics from CC-93538-EE-001 will define the subject demographics for Cohorts 
A through E for CC-93538-EE-002.
Subject demographics from CC-93538-DDI-001 will be 
summarized separately.
OLE baseline will be defined by the last observed measurement captured prior to the OLE Day 1 
administration of CC-93538. Descriptive summaries will be presented. Medical history data will 
be summarized using frequency tabulations by Medical Dictionary for Regulatory Activities 
(MedDRA) system organ class and preferred term.  Additional details are provided in the 
Statistical Analysis Plan (SAP).
9.5
Subject Disposition
Subject disposition, including the number of subjects enrolled, dosed, completing the study and 
discontinuing the study with reasons for discontinuation, will be summarized with numbers and 
percentages by cohorts.
A summary of subjects enrolled by site will be provided. Protocol 
deviations will be summarized using frequency tabulations.
Subjects from CC-93538-DDI-001 will be summarized separately.
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9.6
Efficacy Analysis
Efficacy analyses will be descriptive for each of the pre-defined cohorts (subjects from Study CC-
93538-DDI-001 will be summarized separately) and will include the exploratory endpoints except 
for PK and biomarker endpoints.  The analyses for the PK endpoints and the immunogenicity 
secondary endpoint will be described separately in the PK Analysis Plan.  The biomarker endpoints 
and the related analyses will be described separately in the Biomarker Analysis Plan.  
For continuous endpoints (ie, mean change over time), descriptive statistics including number of 
subjects (n), mean, standard deviation (SD), median, minimum, and maximum will be provided 
by cohort at appropriate time points (for example, OLE Weeks 4, 8, 16, 24, 36, and 48 for the 
mean change in DD).  In addition, the 95% confidence interval (CI) for the mean estimates will be 
presented for the following endpoints:  
 
 the mean change over time 
in the endoscopic features of EoE as measured by the EREFS from baseline, the mean change over 
time in the histologic features of EoE as measured by the EoEHSS from baseline, and the mean 
change over time in mDSD composite score from baseline.
For categorical endpoints (ie, proportions), descriptive statistics including counts and percentages 
will be provided by cohort at each time point.  In addition, the 95% CI for the mean estimates will 
be presented for the following endpoints:  the proportion of subjects with histologic response 
defined as a peak esophageal eosinophil count ≤ 6/hpf and the proportion of subjects with 
histologic response defined as a peak esophageal eosinophil count < 15/hpf.
For subjects who enter the OLE study with clinical, histologic, or clinical and histologic response 
after completing the Maintenance Phase in Study CC-93538-EE-001 (Cohorts C, D and E), the 
durability of response will be reported as the proportion of subjects who continue having their 
clinical, histologic, or clinical and histologic response at each time point, and will be reported by
cohort.
For change from baseline endpoints, details regarding baseline definitions will be described in the 
SAP.
9.7
Safety Analysis
Adverse events will be monitored during the study and the data analyzed with respect to incidence 
as well as severity and potential relationship of the AEs to CC-93538. 
All AEs with a start date before the first open-label dose date, and that are ongoing from a previous 
study to this Open-label Extension study, will be listed in the AE data listing and labeled as “Prior 
Adverse Event.”
Adverse events with an onset on or after the first dose of CC-93538 in this study, or with an onset 
prior to the first dose of CC-93538 that increase in severity on or after the first dose of CC-93538, 
will be considered treatment emergent. Treatment-emergent Adverse events will be summarized 
by system organ class (SOC) and preferred term and presented in descending order of frequency 
within each SOC. Serious AEs, AEs leading to discontinuation of treatment, and AEs leading to 
discontinuation of the study will be summarized similarly.
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Associated laboratory parameters such as hepatic profile, renal function, and hematology values 
will be grouped and presented together. For each laboratory test, individual subject values outside 
the standard reference range will be flagged and listed. Shift tables will be produced showing the 
frequency of shifts from baseline to the lowest and to the highest on-study value in and out of the 
normal range as well as by visit. Changes from baseline to each visit for each laboratory parameter 
will also be summarized.
The change from baseline to each visit for each of the vital sign variables will be summarized. 
Abnormal vital sign values will be flagged and listed.
By-subject listings will be provided for all relevant safety data. Graphical displays and figures 
may be provided where useful to assist in the interpretation of results.
No statistical hypothesis testing will be performed on any safety results.
Overall safety and tolerability will be summarized for each drug presentation (the 360 mg dose of 
CC-93538 administered by 
 injections of 
 mL each at a concentration of 
 mg/mL
CC-93538 or by 
injection of 
mL at a concentration of 
 mg/mL CC-93538 administered 
with the PFS device constituent part or by 
 injection of  mL at a concentration of 
 mg/mL 
CC-93538 administered with the AI device constituent part) utilizing descriptive statistics.
9.8
Interim Analysis
There are no interim analyses planned for this study.
9.9
Other Topics
9.9.1
Pharmacokinetics, Pharmacodynamics and Exposure-Response
Serum trough concentrations (Ctrough) of CC-93538 will be summarized with descriptive statistics
by treatment group as received in the core Induction and Maintenance Study, CC-93538-EE-001,
and by visit.  Ctrough of CC-93538 following administration with the different drug product 
presentations at steady state received in the OLE Study, CC-93538-EE-002, will be summarized 
with descriptive statistics.  Ctrough of CC-93538 for subjects transitioning from the Phase 1 Study, 
CC-93538-DDI-001 will be summarized separately.  Additional analysis may be conducted as 
appropriate (eg, by ADA status).
Population PK analysis will be performed using nonlinear mixed-effects modeling utilizing PK 
data from CC-93538-EE-001 and CC-93538-EE-002 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 in the population PK analysis if appropriate.
Exposure-response and pharmacodynamic relationships will be conducted for efficacy, safety, and 
biomarker endpoints, as appropriate.  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.
9.9.2
Internal Safety Management Team
In addition to ongoing safety monitoring conducted by Investigators and individual study 
personnel, cumulative and interval blinded AEs, SAEs, discontinuations due to AEs, and abnormal
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laboratory findings will be reviewed internally by the Celgene Safety Management Team (SMT).
The SMT is comprised of lead representatives from multiple Celgene functions engaged in the 
CC-93538 development program. 
The scope, conduct, processes, and accountabilities are 
specified by Celgene Standard Operating Procedure (SOP).
9.9.3
External Data Monitoring Committee
Safety monitoring will also be performed by an external, independent Data Monitoring Committee 
(DMC).  A DMC will be convened and will be comprised of physician experts with experience in 
treating subjects with EoE and 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 the 
duration of DMC implementation during the OLE study, will also be described in the DMC 
Charter.
9.9.4
Steering Committee
A Steering Committee, which will include the coordinating Principal Investigator, other 
Investigators, and experts in eosinophilic esophagitis will be empaneled and serve in an advisory 
capacity to the Sponsor. Operational details for the Steering Committee will be detailed in a 
separate Steering Committee Charter.
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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 except for symptoms associated with an EoE flare 
requiring an EoE Flare Assessment, as referenced in Section 6.4.2.7.  However, any EoE flare that 
meets the criteria for serious as detailed in Section 10.2.1, should be documented as an SAE in 
addition to an EoE flare.  A diagnosis or syndrome should be recorded on the AE page of the eCRF 
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 eCRF. (See Section 7.2 for the definition of overdose.) Any sequela of 
an accidental or intentional overdose of an investigational product which meets the definition of 
an AE, should be reported as an AE on the AE eCRF. If the sequela of an overdose meets serious 
criteria, then it must be marked as serious on the eCRF. 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, including AEs related to SARS-CoV-2 infection, 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.  In addition, device (ie, AI)
failures or malfunctions should be captured during the study, and any device related AEs should 
also be documented.  Each study visit will include an assessment for AEs, and subjects who 
develop an intercurrent illness between study visits are encouraged to contact the Investigator, who 
will determine if a clinical assessment is required.  In addition, AEs or SAEs related to SARS-
CoV-2 infection will also trigger additional data collection through supplementary safety report 
forms, which will allow the Sponsor to further evaluate these events.
All AEs, including AEs related to SARS-CoV-2 infection, will be recorded by the Investigator 
from the time the subject signs informed consent/assent (in Study CC-93538-EE-001 or Study CC-
93538-DDI-001) until 16 weeks after the last dose of IP in the OLE study as well as those SAEs 
made known to the Investigator at any time thereafter that are suspected of being related to IP.  
The timing of AE assessment documentation for the OLE study will begin at the time of or after 
the first dose in the OLE study (on OLE Day1); AEs occurring before this timeframe will be 
documented in Study CC-93538-EE-001 or Study CC-93538-DDI-001.  AEs and SAEs will be 
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recorded on the AE page of the eCRF and in the subject’s source documents.  All SAEs must be 
reported to Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the event by 
completing the paper SAE Report Form and sending it directly to Celgene Drug Safety (see Section 
10.5). In addition, COVID-19 or positive SARS-CoV-2 test results should also be reported within 
24 hours of the Investigator’s knowledge of the event regardless of the seriousness criteria.
10.2
Evaluation of Adverse Events
A qualified Investigator will evaluate all AEs as to seriousness, severity/intensity, causality, 
duration, action taken, and outcome. 
10.2.1
Seriousness
An SAE is any AE occurring at any dose that:

Results in death;

Is life-threatening (ie, in the opinion of the Investigator, the subject is at immediate risk of 
death from the AE);

Requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization 
is defined as an inpatient admission, regardless of length of stay);

Results in persistent or significant disability/incapacity (a substantial disruption of the subject’s 
ability to conduct normal life functions);

Is a congenital anomaly/birth defect;

Constitutes an important medical event.
Important medical events are defined as those occurrences that may not be immediately life-
threatening or result in death, hospitalization, or disability, but may jeopardize the subject or 
require medical or surgical intervention to prevent one of the other outcomes listed above.  Medical 
and scientific judgment should be exercised in deciding whether such an AE should be considered
serious.
Events not considered to be SAEs are hospitalizations for:

routine treatment or monitoring of the studied indication not associated with any deterioration 
in condition.

a procedure for protocol/disease-related investigations (eg, surgery, scans, EGD, sampling for 
laboratory tests, bone marrow sampling).  However, hospitalization or prolonged 
hospitalization for a complication of such procedures remains a reportable SAE.

hospitalization or prolongation of hospitalization for technical, practical, or social reasons, in 
absence of an AE.

a procedure that is planned (ie, planned prior to start of treatment on study); must be 
documented in the source document and the eCRF.  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. 
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
emergency outpatient treatment or observation that does not result in admission, unless 
fulfilling other seriousness criteria above.
If an AE is considered serious, the AE screen of the eCRF must be completed and ticked “serious”.
For each SAE, 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 both AEs and SAEs, the Investigator must assess the severity/intensity of the event. 
Mild

Asymptomatic or mild symptoms; clinical or diagnostic observations only

Intervention not indicated

Activities of daily life (ADLs) minimally or not affected

No or minimal intervention/therapy may be required 
Moderate

Symptom(s) cause moderate discomfort

Local or noninvasive intervention indicated

More than minimal interference with ADLs but able to carry out daily social and functional 
activities

Drug therapy may be required
Severe (could be non-serious or serious)

Symptoms causing severe discomfort/pain

Symptoms requiring medical/surgical attention/intervention

Interference with ADLs including inability to perform daily social and functional activities (eg, 
absenteeism and/or bed rest)

Drug therapy is required
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache).  This criterion is not the same as “serious” which is based 
on subject/event outcome or action criteria associated with events that pose a threat to a subject’s 
life or functioning.  
Seriousness, not severity, serves as a guide for defining regulatory obligations.
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10.2.3
Causality
The Investigator must determine the relationship between the administration of the IP and the 
occurrence of an AE/SAE 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 every AE/SAE 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 both AEs and SAEs, 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 an AE or SAE, as applicable (eg, 
discontinuation, interruption, or dose reduction of IP, as appropriate) and report if concomitant 
and/or additional treatments were given for the event. 
10.2.6
Outcome
The Investigator will report the outcome of the event for both AEs and SAEs.  After the initial 
AE/SAE report, the Investigator is required to proactively follow each subject at subsequent 
visits/contacts.  Ongoing AE/SAEs first documented in Study CC-93538-EE-001 or Study CC-
93538-DDI-001 will continue to be followed in the OLE study.  All SAEs, non-serious AEs of 
special interest (as defined in Section 10.6) and SARS-CoV-2 related AEs will be followed until 
resolution, until the condition stabilizes, until the event is otherwise explained, or until the subject 
is lost to follow-up (as defined in Section 11.2).  
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:
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
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 an SAE.
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the eCRF.  If the abnormality was not 
a part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE. 
If possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets).
10.4
Pregnancy
All pregnancies or suspected pregnancies occurring in a female subject of childbearing potential 
are immediately reportable events.  
10.4.1
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 and the subject instructed to 
return any unused portion of the IP to the Investigator. The pregnancy, suspected pregnancy, or 
positive pregnancy test must be reported to 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.
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the Investigator should 
report the abnormal outcome as an AE.  If the abnormal outcome meets any of the serious criteria, 
it must be reported as an SAE to Celgene Drug Safety within 24 hours of the Investigator’s 
knowledge of the event.
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as an SAE.  In addition, any infant death after 28 days that the Investigator suspects is 
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related to the in utero exposure to the IP should also be reported as an SAE to Celgene Drug Safety 
within 24 hours of the Investigator’s knowledge of the event.
10.5
Reporting of Serious Adverse Events
Any AE that meets any criterion for an SAE requires the completion of the AE page/screen of the 
eCRF, and the AE ticked as “serious” in the electronic data capture system (EDC). All SAEs must 
be reported to Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the event
per the instruction provided on Celgene’s Serious Adverse Event Report Form Completion 
Guidelines. This instruction pertains to initial SAE reports as well as any follow-up reports.
For Study CC-93538-EE-002, the reporting of SAE data (both initial and follow-up) to Celgene 
Drug Safety, will transition to a paper format rather than the electronic format being utilized in the 
parent studies (CC-93538-EE-001 and CC-93538-DDI-001). The Investigator is required to ensure 
that the data on the paper SAE Report Form is accurate and consistent.  In Study CC-93538-EE-
002, this requirement applies to all SAEs (regardless of relationship to IP) that occur during the 
study (from the time the subject receives the first dose of IP [on OLE Day 1] until 16 weeks after 
the last dose of IP [through the Final 16-week Safety Follow-up Visit]) or any SAE made known 
to the Investigator at any time thereafter that are suspected of being related to IP.  Serious adverse 
events occurring prior to the first dose of OLE IP administration, but after signing the OLE 
ICF/assent, will be recorded on the appropriate eCRF of the parent study (CC-93538-EE-001 or 
CC-93538-DDI-001). Therefore, for SAEs occurring prior to the first dose of IP in the OLE study 
(OLE Day 1), the SAE onset date will be recorded in the appropriate parent study (CC-93538-EE-
001 or CC-93538-DDI-001) and reported to Celgene Drug Safety per the instructions provided in 
those protocols. Ongoing AEs/SAEs first documented in Study CC-93538-EE-001 or Study CC-
93538-DDI-001 will then continue to be followed in the OLE study.  
The SAE report should provide a detailed description of the SAE and include a concise summary 
of hospital records and other relevant documents. If a subject died and an autopsy has been 
performed, copies of the autopsy report and the death certificate are to be provided to Celgene 
Drug Safety as soon as these become available. Any follow-up data should be detailed in a 
subsequent SAE Report Form, or approved equivalent form, and sent directly to Celgene Drug 
Safety. Follow-up safety data should also be recorded in the eCRF, as applicable.
Where required by local legislation, the Investigator is responsible for informing the Institutional 
Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with all relevant initial 
and follow-up information about the event. The Investigator must keep copies of all SAE 
information on file including correspondence with Celgene and the IRB/EC.
10.5.1
Safety Queries
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via 
facsimile or electronic mail. The response time is expected to be no more than 5 business days. 
Urgent queries (eg, missing causality assessment) may be handled by phone.
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10.6
Adverse Events of Special Interest
Investigators should identify AEs that meet the following criteria for adverse events of special 
interest (AESIs). All AESIs must be reported to the EDC within 24 hours of the Investigator’s 
knowledge of the event.  Additionally, AESIs will be identified by the Sponsor programmatically. 
AESIs fall into a number of categories based on the safety observations from dupilumab, 
lebrikizumab, and CC-93538 clinical studies and the potential pharmacologic effects of IL-4 
receptor antagonist and anti-IL-13 antibodies. These include:
10.7
Expedited Reporting of Adverse Events
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to CC-93538 based on the Investigator’s Brochure.
In the US, expedited reports sent to the Food and Drug Administration (FDA) by the Sponsor 
based on the reasonable possibility threshold are known as ‘IND safety reports’ and will be 
reported in accordance with 21 Code of Federal Regulations (CFR) 312.32.  For reporting to the 
FDA, events that are not suspected to be causally related to CC-93538 by the Sponsor will not be 
considered adverse reactions.  As per FDA regulations, events that are anticipated in the study 
population, will not be considered adverse reactions on individual assessment and will be reviewed 
on an aggregate basis for assessment of frequency.  
For countries within the European Economic Area (EEA), Celgene or its authorized representative 
will report in an expedited manner to Regulatory Authorities and Ethics Committees concerned, 
suspected unexpected serious adverse reactions (SUSARs) in accordance with Directive 
2001/20/EC and the Detailed Guidance on collection, verification and presentation of adverse 
reaction reports arising from clinical trials on investigational products for human use (ENTR/CT3) 
and also in accordance with country-specific requirements.  
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Celgene or its authorized representative shall notify the Investigator of the following information
(in Japan, Celgene KK shall notify the Heads of the Institutes in addition to the Investigators):

Any AE suspected of being related to the use of IP in this study or in other studies that is both 
serious and unexpected (ie, SUSAR);

Any finding from tests in laboratory animals that suggests a significant risk for human subjects 
including reports of mutagenicity, teratogenicity, or carcinogenicity.

Other important safety information and periodic reports according to the local regulations.
Where required by local legislation, the Investigator shall notify his/her IRB/EC promptly of these 
new serious and unexpected AE(s) or significant risks to subjects.
The Investigator must keep copies of all pertinent safety information on file including 
correspondence with the IRB/EC. (See Section 13.3 for record retention information).
Celgene Drug Safety Contact Information:
For Celgene Drug Safety contact information, please refer to the Pregnancy Report Form 
Completion Guidelines.
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11
DISCONTINUATIONS
11.1
Treatment Discontinuation
The following events are considered sufficient reasons for permanently discontinuing a subject 
from CC-93538:

Adverse event 

Physician decision

Lack of efficacy

Protocol deviation that may impact subject safety

Withdrawal by subject or parent/guardian

Death

Lost to follow-up

Non-compliance with IP 

Other (to be specified on the eCRF)
The following events require permanent discontinuation of CC-93538 (permanent discontinuation 
of CC-93538 will result in study discontinuation):
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Note:  INR is part of the coagulation panel and may be obtained at the discretion of the Investigator 
via central or local laboratory testing.
Subjects who are permanently discontinued from CC-93538 will also be discontinued from the 
study (see Section 11.2).
The reason for discontinuation of treatment should be recorded in the eCRF 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 from treatment, 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

Lack of efficacy

Protocol deviation that may impact subject safety

Withdrawal by subject or parent/guardian

Death

Lost to follow-up

Non-compliance with IP 

Other (to be specified on the eCRF)

Events requiring permanent CC-93538 discontinuation as listed in Section 11.1 will result in 
study discontinuation
Subjects who demonstrate a persistent lack of improvement or worsening of EoE symptoms should 
be discontinued.  While subjects will have the opportunity to continue participation in the OLE 
with use of rescue therapy as needed, based on clinical judgment, the Investigator should 
discontinue any subject in which study participation no longer is in the best interest of the subject.   
During 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. 
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.  
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For the OLE study, subjects who discontinue the study will have an ET/EoT Visit within 2 weeks 
after final CC-93538 administration and an Interim 8-week and Final 16-week Safety Follow-up 
Visit at 8 weeks and at 16 weeks, respectively, after final CC-93538 administration for the 
assessment of safety and clinical status. Assessments should be performed in accordance to the 
Table of Events (Table 3).
11.3
Emergency Contact
In emergency situations, the Investigator should contact the responsible Clinical Research 
Physician (also referred to as Clinical Trial 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 (also referred to as Clinical Trial 
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), also referred to as Clinical Trial Physician(s), 
or Medical Monitor or designee for emergency calls. 
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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 for
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/assent) 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 eCRFs 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/assent of a subject and/or a subject’s legal 
representative prior to any study related procedures. Adolescent subjects must agree to participate 
in the study by signing an assent form. A parent/legal representative of an adolescent subject must 
sign an informed consent form.  Adolescent subjects who reach the legal age of consent while 
participating in the study will be asked to sign an ICF (referred to as a Transitional ICF) themselves 
to acknowledge their willingness to continue in the study.  For the purposes of this study, 
adolescents are defined as subjects aged 12 to 17 years at the time of signing the assent form in 
Study CC-93538-EE-001 (except where national or regional guidelines for the definition of 
adolescence differ from the definition stated above).  As described in the Transitional ICF, subjects 
who enter the study as adolescents should continue to complete the assessments specific for 
adolescents throughout both CC-93538-EE-001 and CC-93538-EE-002 and do not need to 
complete assessments that are only required in adult subjects.  In Austria, Germany, Spain, and 
Switzerland, adolescent subjects will not be enrolled.
Documentation that informed consent/assent occurred prior to the study subject’s entry into the 
study and of the informed consent/assent process should be recorded in the study subject’s source 
documents including the date.  The original ICF/assent 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/assent, the 
ICF/assent must be revised.  Study subjects participating in the study when the amended protocol 
is implemented must be re-consented/assented with the revised version of the ICF/assent. The 
revised ICF/assent 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/assent, 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
(also referred to as Clinical Trial 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 
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applicable. Amendments that are administrative in nature do not require IRB/EC approval but will 
be submitted to the IRB/EC for information purposes.
12.6
Institutional Review Board/Independent Ethics Committee Review and 
Approval
Before the start of the study, the study protocol, ICF/assent, 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 
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/assent 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.
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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 non-compliance;

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 eCRFs/case report forms (CRFs) or CD-ROM.
13.2
Data Management
Data will be collected via eCRF 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/assent 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).
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. 
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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, eCRFs, 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, 
eCRFs, 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 eCRFs 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 eCRFs 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 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, eCRFs and applicable supporting records of study subject participation for 
audits and inspections by IRB/ECs, regulatory authorities (eg, FDA, European Medicines Agency 
[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), also referred to as IP, safety, 
purity, potency, quality and identity (eg, 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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17
APPENDICES
APPENDIX A
TABLE OF ABBREVIATIONS
Table 4:
Abbreviations and Specialist Terms
Abbreviation or 
Specialist Term
Explanation
ADA
Anti-drug antibody
ADL
Activities of daily life
AE
Adverse event 
AESI
Adverse events of special interest
AI
Autoinjector
ALT
Alanine aminotransferase
AMS
Avoidance, modification, and slow eating
AST
Aspartate aminotransferase
AUC
Area under the curve
AxMP
Auxiliary medicinal product 
β-hCG
β-subunit of human chorionic gonadotropin
BMS
Bristol-Myers Squibb
CFR
Code of Federal Regulations
CGI-S
Clinician Global Impression of Severity
CI
Confidence interval
Cmax
Observed maximum serum concentration
COVID-19
Coronavirus disease 2019
CPK
Creatine phosphokinase
CRF
Case report form
CRP
C-reactive protein
CSR
Clinical study report
Ctrough
Serum trough concentration
CYP
Cytochrome P450
DB
Double-blind
DD
Dysphagia day(s)
DMC
Data Monitoring Committee
DSD
Daily Symptom Diary
EC
Ethics Committee
EC50
Half maximal effective concentration
eCRF
Electronic case report form
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Table 4:
Abbreviations and Specialist Terms
Abbreviation or 
Specialist Term
Explanation
EDC
Electronic data capture system
eDiary
Electronic diary
EEA
European Economic Area
EEsAI
Eosinophilic Esophagitis Activity Index
EGD
Esophagogastroduodenoscopy
EMA
European Medicines Agency
EMT
Epithelial mesenchymal transition
EndoFLIP
Endolumenal Functional Lumen Imaging Probe
EoE
Eosinophilic esophagitis
EoEHSS
EoE histology scoring system
EoT
End of Treatment
EREFS
EoE Endoscopic Reference Score
ET
Early Termination
EU
European Union
FCBP
Female of childbearing potential
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GERD
Gastroesophageal reflux disease
GGT
Gamma glutamyltransferase
GI
Gastrointestinal
GIC-EoE
Global Impression of Change in EoE symptoms
H&E
Hematoxylin and eosin
Hct
Hematocrit
Hgb
Hemoglobin
HIV
Human immunodeficiency virus
hpf
High-power field 
HRQoL
Health-related quality of life
IB
Investigator's Brochure
ICF
Informed Consent Form
ICH
International Council for Harmonisation
IFNα
Interferon alpha
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Table 4:
Abbreviations and Specialist Terms
Abbreviation or 
Specialist Term
Explanation
IgE
Immunoglobulin E
IgG
Immunoglobulin G
IgG1
Immunoglobulin G1
IgG1κ
Immunoglobulin G1 kappa
IL-4
Interleukin-4
IL-5
Interleukin-5
IL-13
Interleukin-13
IL-13Rα1
Interleukin-13 receptor alpha 1
IL-13Rα2
Interleukin-13 receptor alpha 2
IL-17
Interleukin-17
IMP
Investigational medicinal product
INR
International normalized ratio
IP
Investigational product
IRB
Institutional Review Board
IUD
Intrauterine device
IUS
Intrauterine hormone-releasing system
IV
Intravenous/ly
JAK
Janus kinase
LA
Los Angeles
mAb
Monoclonal antibody
MCH
Mean corpuscular hemoglobin 
MCHC
Mean corpuscular hemoglobin concentration
MCV
Mean corpuscular volume
mDSD
Modified Daily Symptom Diary
MedDRA
Medical Dictionary for Regulatory Activities
N / n
Number of subjects
NIMP
Non-investigational medicinal product
OLE
Open-label Extension
OTC
Over the counter
PDE
Phosphodiesterase
PEESS
Pediatric Eosinophilic Esophagitis Symptom Severity Module
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Table 4:
Abbreviations and Specialist Terms
Abbreviation or 
Specialist Term
Explanation
PFS
Pre-filled syringe(s)
PGI-S
Patient Global Impression of Severity
PK
Pharmacokinetic(s)
PPI
Proton pump inhibitor
QW
Once weekly
Q2W
Once every 2 weeks (ie, once every other week)
RBC
Red blood cell
SAE
Serious adverse event
SAP
Statistical Analysis Plan
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 
SC
Subcutaneously/subcutaneous (dose/injection)
SD
Standard deviation
SF-10
10-Item Short Form Health Survey for Children
SF-12v2
12-Item Short Form Health Survey
SGOT
Serum glutamic oxaloacetic transaminase 
SGPT
Serum glutamic pyruvic transaminase
SMT
Safety Management Team
SNP
Single nucleotide polymorphism
SOC
System organ class
SOP
Standard operating procedure
SUSAR
Suspected unexpected serious adverse reaction
t½
Terminal elimination half-life
TB
Tuberculosis
TEAE
Treatment-emergent adverse event
Th2
Type 2 T helper (cell)
tmax
Time to the observed maximum concentration
TNF
Tumor necrosis factor alpha
US
United States
VDQ
Visual dysphagia question  
WBC
White blood cell
WPAI:SHP
Work Productivity and Activity Impairment Questionnaire: Specific Health Problem
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APPENDIX B
MODIFIED DAILY SYMPTOM DIARY (MDSD)
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CC-93538-EE-002 Amendment 1
Final: 10 May 2022
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OVERALL RATIONALE FOR PROTOCOL AMENDMENT 1:
This global protocol amendment 1 is created to support the introduction of a new presentation of 
CC-93538 
 pre-filled syringe (PFS) at a concentration of
. The new presentation
allows subjects to receive the 360 mg weekly dose of CC-93538 by a 
 subcutaneous (SC)
injection. This protocol amendment also allows subjects who complete the Phase 1 Study
CC-93538-DDI-001 the opportunity to transition to Study CC-93538-EE-002 and continue to
receive access to open-label CC-93538. Additionally, details regarding the timing of and the
assessments for those subjects transitioning from Study CC-93538-DDI-001 into the Open-label
Extension (OLE) study are included.
The following summary of changes outline the revisions to the various sections of the original 
protocol.
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 1
Section Number & 
Title
Description of Change
Brief Rationale
Title Page and 
Signature Pages
Sponsor address and personnel 
changes.
Administrative changes.
Title Page; 
Protocol Summary; 
Section 1.2.1:
Mechanism of Action
Bristol-Myers Squibb (BMS) 
compound number added.
For clarification purposes.
Protocol Summary
Language has been added regarding 
study eligibility, clarifying that in 
Germany, Spain, and the United 
Kingdom, only subjects who have 
had an inadequate response to 
corticosteroids or are intolerant to 
corticosteroids will be enrolled in 
the Phase 3 Studies CC-93538-EE-
001 and CC-93538-EE-002.  
Local restrictions prohibit 
enrollment of subjects who 
are naive or have had an 
adequate response to 
corticosteroids in Germany, 
Spain, and the United 
Kingdom.
Language has been updated to 
indicate that in Austria, Germany, 
Spain, and Switzerland, only adult 
subjects will be enrolled, and 
adolescent subjects will not be 
included in the Phase 3 Studies CC-
93538-EE-001 and CC-93538-EE-
002.
Local restrictions prohibit 
enrollment of adolescent
subjects in Germany and 
Spain. Adolescents will not 
be enrolled in Austria or 
Switzerland as participating 
sites in these countries do not 
serve the adolescent patient 
population or have decided to 
only enroll adult patients.
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CC-93538-EE-002 Amendment 1
Final: 10 May 2022
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 1
Section Number & 
Title
Description of Change
Brief Rationale
Section 1.2.2: Clinical 
Studies
New protocol Section 1.2.2.4 
(Phase 1 Study, CC-93538-CP-002) 
has been added. 
To include the results of 
Study CC-93538-CP-002,
which provide the 
pharmacokinetic (PK)
comparability, safety, 
tolerability, and 
immunogenicity of a single 
SC dose of 360 mg CC-93538
using 2 different drug 
concentrations, 180 mg/mL 
and 150 mg/mL, in healthy 
adult subjects.
Protocol Summary;
Section 1.3.1: Study 
Rationale and Purpose;
Section 1.3.2:
Rationale for the Study 
Design;
Section 3.2: Open-label 
Extension Study 
Design; 
Section 3.2.1: Open-
label Treatment Period;
Section 3.3: Study 
Duration for Subjects; 
Section 4.1: Number of 
Subjects;
Section 4.2: Inclusion 
Criteria (1, 2, 3, 4a);
Section 4.3: Exclusion 
Criteria; (6, and 14)
Section 5: Table of 
Events;
Section 8.2: Prohibited 
Concomitant 
Medications and 
Procedures;
Section 9.1: Overview;

New language was added for 
subjects who complete Study 
CC-93538-DDI-001 and are 
eligible to transition to Study 
CC-93538-EE-002.

Open-label Extension Study 
Schema (Figure 2) was updated 
to include subjects from Study 
CC-93538-DDI-001 who 
complete Period 2 and are 
eligible to transition to Study 
CC-93538-EE-002. 

New Inclusion Criterion 1b was 
added, and Inclusion Criteria (2, 
3, and 4a), Exclusion Criteria (6 
and 14), and footnotes for Table 
3 (Table of Events for the 
Open-label Extension Study) 
were updated to reflect Study 
CC-93538-DDI-001 details.
In addition to subjects 
participating in the Induction 
and Maintenance Study 
CC-93538-EE-001, subjects 
who participate in the Phase 1 
Study CC-93538-DDI-001 
and complete Period 2 will be 
offered the opportunity to 
transition into Study 
CC-93538-EE-002, allowing 
for continued access to 
CC-93538.  
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CC-93538-EE-002 Amendment 1
Final: 10 May 2022
10
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 1
Section Number & 
Title
Description of Change
Brief Rationale
Section 9.3: Sample 
Size and Power 
Considerations; 
Section 10.2.6: 
Outcome
Section 1.3.1.1:
Benefit-Risk 
Assessment;
Section 8.1: Permitted 
Concomitant 
Medications and 
Procedures
Information related to concomitant 
use of coronavirus disease 2019 
(COVID-19) vaccines in subjects 
receiving CC-93538 was added. 
Non-live COVID-19 
vaccinations will be allowed 
and will be documented as a 
concomitant medication for 
this study.  The efficacy and 
safety of non-live vaccines 
(including non-live COVID-
19 vaccines) in subjects 
receiving CC-93538 remain 
unknown at this time.
Section 1.3.3:
Rationale for Dose, 
Schedule and Regimen 
Selection;
Section 2: Study 
Objectives and 
Endpoints; 
Section 5: Table of 
Events;
Section 6.2: Open-label 
Extension Treatment 
Period;
Section 6.9: Subject-
Reported Outcomes;
Section 7.1:
Description of 
Investigational 
Product(s);
Section 7.2: Treatment 
Administration and 
Schedule

Language was added to
describe the introduction of the
 of the 
 PFS, which is
replacing the
 that were
administered in Study CC-
93538-EE-001 and the original
protocol for Study CC-93538-
EE-002.

For subjects currently enrolled
in the study, added language
states the timing for the switch
to the new presentation will
occur at the subject’s next
scheduled visit, and the first
dose will be administered
during an in-clinic visit for all
subjects to ensure accurate dose
administration and compliance.

A new exploratory objective
and study endpoint were added
to evaluate the successful self-
administration of CC-93538
using the new 

Upon the implementation
of this amendment, the
CC-93538 360 mg SC
dose will be administered
by 
 of 
 provided in a 
 PFS in order
to study the higher
concentration and higher
volume presentation for
use with long-term CC-
93538 treatment.

The PFS Administration
Questionnaire is
introduced to assess
subjects’ success in self-
administration of
CC-93538 by the new
 PFS
presentation in-clinic or at
home.
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CC-93538
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 1
Final: 10 May 2022
11
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 1
Section Number & 
Title
Description of Change
Brief Rationale
PFS presentation by 
 
.


New protocol Section 6.9.2:
PFS Administration
Questionnaire has been added.
Section 3.2: Open-label 
Extension Study 
Design;
Section 4.1: Number of 
Subjects; 
Section 4.2: Inclusion 
Criteria (Inclusion 
Criterion 7); 
Section 6: Procedures;
Section 12.3: Subject 
Information and 
Informed Consent
Protocol sections were updated to 
indicate that in Austria, Germany, 
Switzerland, and Spain, only adult 
subjects will be enrolled, and 
adolescent subjects will not be 
included in the Phase 3 Studies 
CC-93538-EE-001 and CC-93538-
EE-002.
Local restrictions prohibit 
enrollment of adolescent
subjects in Germany and 
Spain. Adolescents will not 
be enrolled in Austria or 
Switzerland as participating 
sites in these countries do not 
serve the adolescent patient 
population or have decided to 
only enroll adult patients.
Section 4.2: Inclusion 
Criteria
The sentence in Inclusion Criterion 
7) regarding legal maturity in Japan
at the age of 20 was removed to
reflect a change in the country’s
age of legal maturity.
Updates were made to reflect 
country specific requirements. 
Section 4.3: Exclusion 
Criteria 
With respect to gastritis, Criterion 
8) was updated to clarify that only a
medical diagnosis of gastritis which
is deemed by the Investigator to be
clinically significant is
exclusionary.
As the term “gastritis” may 
have a broader meaning 
including multiple 
gastrointestinal symptoms, the 
criterion is revised to clearly 
define the condition for study 
eligibility.
Section 5: Table of 
Events;
Section 6.4.2.4: Global 
Impression of Change 
in EoE Symptoms 
(GIC-EoE);

Table 3 (Table of Events for the
Open-label Extension Study)
now provides additional
footnotes for the Global
Impression of Change in
Eosinophilic Esophagitis

For subjects transitioning
from Study CC-93538-
DDI-001, not all
assessments will be
required: GIC-EoE and
EndoFLIP will not be
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CC-93538
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 1
Final: 10 May 2022
12
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 1
Section Number & 
Title
Description of Change
Brief Rationale
Section 6.11:
Endolumenal 
Functional Lumen 
Imaging Probe 
(EndoFLIPTM) Sub-
study
Symptoms (GIC-EoE) and the 
EndoFLIP (optional sub-study).

EndoFLIP procedure
instructions were removed from 
the protocol. 
conducted in these 
subjects, as no baseline 
assessment will be 
available.

Complete EndoFLIP 
procedure instructions will 
be included in a separate 
manual. 
Section 5: Table of 
Events;
Section 6.7.2: Tissue 
Biomarker 
Assessments
Section 6.7.2 and Table 3 were
updated to clarify that esophageal 
tissue biomarkers will not be 
assessed in subjects transitioning 
from Study CC-93538-DDI-001. 
Esophageal tissue biomarkers 
will not be assessed in 
subjects transitioning from 
Study CC-93538-DDI-001 as 
there is no baseline measure, 
precluding the assessment of 
any post-baseline changes.
Section 5: Table of 
Events;
Section 6.2: Open-label 
Extension Treatment 
Period
Details have been added regarding 
subjects who transition from Study 
CC-93538-DDI-001 into the OLE 
study. 
To provide requirements for 
OLE Day 1/Baseline 
assessments for patients 
transitioning from Study CC-
93538-DDI-001 to OLE 
Study CC-93538-EE-002 as 
well as assessments that will 
not be required during the 
study for those subjects 
transitioning from CC-93538-
DDI-001. 
Language has been added regarding 
pregnancy testing for subjects who 
transition from Study CC-93538-
DDI-001 into the OLE study.
For subjects transitioning 
from Study CC-93538-DDI-
001, if a pregnancy test has 
not been completed on the 
same day of OLE Day 1, then 
a pregnancy test in urine or 
serum must be repeated prior 
to dosing.
Section 6.9.1: Health-
related Quality of Life
Language has been included to state 
that Work Productivity and Activity 
Impairment Questionnaire: Specific 
Health Problem (WPAI:SHP) is 
also referred to as WPAI:
Eosinophilic Esophagitis (EE).
To clarify the name change of 
the instrument in the 
electronic data capture system
(EDC) to denote EoE as the 
specific health problem.
1.0
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Approved
1.0
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CC-93538
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 1
Final: 10 May 2022
13
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 1
Section Number & 
Title
Description of Change
Brief Rationale
Section 7.2.1: Self-
Administration
Clarification has been provided
regarding a switch from in-clinic or 
home health nurse service to self-
administration.
Subjects that transitioned 
from the parent studies to the 
OLE study will be allowed to 
switch their method of 
administration (eg, from in-
clinic or home health nurse 
service to self-administration) 
based on Investigator 
judgment.
Protocol Summary;
Section 9.2: Study 
Population Definitions;
Section 9.4:
Background and 
Demographic 
Characteristics; 
Section 9.5: Subject 
Disposition; 
Section 9.6: Efficacy 
Analysis
Language was added to clarify that 
data collected for subjects who 
transitioned from Study CC-93538-
DDI-001 will be summarized
separately from subjects who
transitioned from CC-93538-EE-
001.
Data for subjects who
transitioned from the two 
parent studies will be 
summarized separately
because of the difference in 
prior CC-93538 treatment 
durations.
Section 9.7: Safety 
Analysis
Clarification has been provided, 
stating that the overall safety and 
tolerability data will be summarized 
by presentation utilizing descriptive 
statistics. 
Text was added to describe 
the assessment of the safety 
profile of CC-93538 based on 
PFS presentation the subjects 
received during the trial.
Section 10: Adverse 
Events;
Section 10.5: Reporting 
of Serious Adverse 
Events
Modifications were made for 
reporting of serious adverse events
(SAEs), adverse events of special 
interest (AESI), and adverse events 
(AEs) related to severe acute 
respiratory syndrome coronavirus 2 
(SARS-CoV-2) infection using a
paper reporting form.
All SAEs must be reported to 
Celgene Drug Safety within 
24 hours of the Investigator’s 
knowledge of the event by 
completing the paper SAE 
Report Form and sending it 
directly to Celgene Drug 
Safety. This reporting 
process aligns with company 
policy, namely that open-label 
extension studies will not 
utilize the electronic safety 
reporting process.
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930185673
1.0
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Approved
1.0
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CC-93538
Protocol CC-93538-EE-002
Celgene International II Sàrl
CC-93538-EE-002 Amendment 1
Final: 10 May 2022
14
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 1
Section Number & 
Title
Description of Change
Brief Rationale
Section 10.5.1: Safety 
Queries
Details for reporting SAEs and 
urgent safety queries have been
added.
Guidance is provided that 
urgent queries (eg, missing 
causality assessment) may be 
reported by phone.
Section 10.7:
Expedited Reporting of 
Adverse Events
Gastroesophageal reflux disease 
(GERD) and dysphagia are not 
considered anticipated serious 
events, and as such they will not be 
excluded from expedited reporting 
of AEs to the United States Food 
and Drug Administration (US 
FDA) per the CC-93538 Safety 
Surveillance Plan.
Per the Safety Surveillance 
Plan for CC-93538, following 
review of data from 
randomized controlled trials
in EoE, including Study 
RPC02-201, anticipated 
severe events have not been 
identified for the EoE patient 
population; therefore, 
dysphagia and GERD are 
being removed as serious 
anticipated events from the
CC-93538-EE-002 protocol.
All
Minor formatting and editorial
changes have been made.
Minor edits that do not 
change the content of the 
protocol were made to 
improve readability and 
consistency.
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Approved
1.0
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