A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Induction and Maintenance Study to Evaluate the Efficacy and Safety of CC-93538 in Adult and Adolescent Japanese Subjects With Eosinophilic Gastroenteritis
Phase: PHASE3
Conditions: Eosinophilic Gastroenteritis
Sponsor: Celgene

Official Title of Study: 
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Induction and Maintenance 
Study to Evaluate the Efficacy and Safety of CC-93538 in Adult and Adolescent Japanese Subjects 
with Eosinophilic Gastroenteritis 
 
NCT Number: NCT05214768 
Document Date (Date in which document was last revised): 20 Sep 2023 
 
 
 

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
1
A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED INDUCTION AND MAINTENANCE
STUDY TO EVALUATE THE EFFICACY AND SAFETY OF CC-
93538 IN ADULT AND ADOLESCENT JAPANESE SUBJECTS 
WITH EOSINOPHILIC GASTROENTERITIS
PROTOCOL NUMBER:
CC-93538-EG-001
COMPOUND NUMBER:
DATE FINAL:
CC-93538 (BMS-986355)
02 Mar 2021
DATE AMENDMENT 1.0 FINAL
29 Jun 2021
DATE AMENDMENT 2.0 FINAL
27 Aug 2021
DATE AMENDMENT 3.0 FINAL
28 Oct 2021
DATE AMENDMENT 4.0 FINAL
07 Dec 2022
DATE AMENDMENT 5.0 FINAL
20 Sep 2023
EudraCT NUMBER:
NA
IND NUMBER:
NA
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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Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
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MEDICAL MONITOR/EMERGENCY CONTACT INFORMATION 
Contact Information:
Name:
Title:
Clinical Trial Physician, 
Address:
Phone:
(Cell)
E-mail:
Note: The back-up 24-hour global emergency contact call center should only be used if you 
are not able to reach the Clinical Trial Physician(s) or Medical Monitor or designee for 
emergency calls.
Back-up 24-hour Global Emergency Contact Call Center: 
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Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
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CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE
See Electronic Signature and Date on File in Electronic 
Document Management System.
Signature of Celgene Therapeutic Area Head
dd mmm yyyy
Printed Name of Celgene Therapeutic Area Head and Title
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable. 
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Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
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SPONSOR: CELGENE INTERNATIONAL II SÀRL
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Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 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-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 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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Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
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OVERALL RATIONALE FOR PROTOCOL AMENDMENT 5.0:
Protocol Amendment 5 is being implemented to support the introduction of a new 
 
 presentation for administration of CC-93538 (BMS-986355) as a weekly subcutaneous (SC) 
dose by a single 2 mL injection at a concentration of 180 mg/mL. The details on the transition of 
current and new subjects to the new 
 presentation, timing of visits, 
 
 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 
 and pre-filled syringe (PFS) presentations. Additionally, there are minor 
clarification and administrative updates that have been included in this Amendment.
The following summary of changes outlines the revisions to the various sections of Protocol 
Amendment 5.
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 5.0
Section Number & 
Title
Description of Change
Brief Rationale
Throughout
In the OLE Phase, the description 
about 
 has been 
added 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 
 
presentation in the OLE Phase.
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.
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 single 
subcutaneous (SC) injections 
of CC-93538 administered 
using an 
 versus PFS.
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Protocol CC-93538-EG-001
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Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 5.0
Section Number & 
Title
Description of Change
Brief Rationale
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 evaluatingCC-
93538 for moderate-to-severe 
atopic dermatitis.
Section 1.2.2.6, Phase 1 
Study, IM042-003
Section 1.3.2, 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 single dose 360 mg/2 mL 
 
presentation.
To include the preliminary 
results of Phase 1 Study 
IM042-003 Part 1, which 
provides PK comparability, 
safety, tolerability, and 
immunogenicity of single SC 
injections of CC-93538 
administered using an 
 
versus PFS.
The results of Study IM042-
003 support the introduction of 
the single dose 360 mg/2 mL 
 presentation in Protocol 
Amendment 5.
Table 1, Study 
Objectives
Table 2, Study 
Endpoints
A new 
 objective and 
endpoint has been added  
 
 
To account for the change in 
the presentation of 
administration of CC-93538 
.
Section 3.1.1, 
Screening Period
Section 4.2, Inclusion 
Criterion 4
Table 4, Table of 
Events for the Induction 
Phase; footnote “q”
Section 6.4.2.1, Izumo 
Scale Questionnaire
Clarified that the Izumo Scale data 
collected before the 
investigational product (IP)
administration on Day 1 can be 
used for confirming eligibility of 
study participation. 
For clarification purposes.
Section 3.1.4, Open-
label Long-term 
Extension Phase
Table 6, Table of 
Events for the Open-
Increased the maximum 
acceptable interval between the 
last dose of investigational 
product (IP) in the Induction
Phase or the Maintenance Phase to 
Accounting for unavoidable 
situations that may cause 
delays in the first dose in OLE 
(eg. coronavirus disease 2019 
restrictions, unavailability of 
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Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 5.0
Section Number & 
Title
Description of Change
Brief Rationale
label Long-term 
Extension (OLE)
Section 6.3.2, Open-
label Long-term 
Extension (OLE) Phase
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 the Induction
Phase or the Maintenance Phase, 
unless discussed with the Medical 
Monitor.
IP supplies, scheduling issues) 
and for increased flexibility for 
sites to enroll subjects on this 
study and receive CC-93538.
Section 3.1.6, 
Worsening of EGE
Symptoms or Lack of 
Improvement
Section 6.4.2.7, 
Worsening of EGE 
Symptoms, EGE Flare, 
the EGE 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 EGE symptoms in 
the OLE Phase. 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.
Table 6, Table of 
Events for the Open-
label Long-term 
Extension (OLE)
•
Included an additional 
Administration Visit for
switching to the new IP
presentation.
•
Footnote “y” added to provide
the window for the First 
Administration Visit.
 
 
 
•
This First 
Administration Visit is
being added to expedite the
switch to the new 
presentation for subjects
whose next scheduled visit
is not within 4 weeks of the
Protocol Amendment 5
implementation and IP
availability at the site.
 
 
 
Table 6, Table of 
Events for the Open-
label Extension (OLE)
•
Additional time points added
for serum CC-93538 PK
assessment at Week 36 of
Year 1 and at 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-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 5.0
Section Number & 
Title
Description of Change
Brief Rationale
•
Additional time points added
for serum antibodies to CC-
93538 assessment at Week 36
of Year 1 and at the Q1 and
Q3 Visits at Year 2 and
beyond.
Section 6.1.2,
Screening Failures and 
Rescreening of 
Potential Subjects
Updated to clarify that the most 
current results prior to dosing on 
Day 1 will be used to assess study 
inclusion if more than one set of 
laboratory tests are drawn.
For clarification purposes.
Section 6.2, Induction 
Phase and Maintenance 
Phase
Provided guidance regarding the 
Week 16 dose when out of 
window due to EGD scheduling.
For clarification purposes.
Section 6.2.1, EGE 
Flare Assessment Visit
•
Provided guidance regarding
Week 16/Week 48 Visit EGD
requirements for subjects that
had an EGD as part of their
EGE Flare assessment.
•
Note added to clarify that
samples do not need to be a
pre-dose draw unless the
subject is expected to dose
later that day.
For clarification purposes.
Section 6.3.2, Open-
label Long-term 
Extension (OLE) Phase
•
Discussion with Medical
Monitor was added if there is a
delay of > 21 days from CC-
93538 dosing in the Induction
Phase or the Maintenance
Phase to enrollment in the
OLE Phase.
•
Revised and provided
additional guidance on the
baseline
esophagogastroduodenoscopy
(EGD) at Day 1.
•
Change in the number of
days to align with the
longest window allowed
between dosing in the
Induction Phase or the
Maintenance Phase.
•
To provide further
clarification on the timing
of the baseline EGD
procedure in the OLE
Phase.
•
Overall simplification of
text and consolidation of
information to the Table of
Events.
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Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 5.0
Section Number & 
Title
Description of Change
Brief Rationale
 
 
Section 6.4.1,
Esophagogastroduoden
oscopy (EGD)
Added clarification for handling 
incidental findings of potential 
clinical relevance not associated 
with objectives of the study.
For clarification purposes.
Section 6.4.2.2, EGID 
Severity Score
Clarified that the scoring tables 
(Appendix C and D) used in this 
study refer to the ones posted on 
"Eosinophilic Gastro-Intestinal 
Disorder" disclosed by Japan 
Intractable Diseases Information 
Center.
For clarification purposes.
Section 6.4.2.11, Entry 
to Maintenance Phase
Included language to state that if 
the subject is eligible for the 
Maintenance Phase, but the 
investigator does not believe it is 
in the best interest of the subject 
to continue, a discussion with the 
Medical Monitor will be required 
prior to transitioning into the 
Open-Label Extension Phase.
Language for entry into the 
Maintenance Phase was 
updated to clarify that this 
decision should be made in 
conjunction with the Medical 
Monitor.
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.
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Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 5.0
Section Number & 
Title
Description of Change
Brief Rationale
Section 7.1, Description 
of Investigational 
Product(s)
CC-93538 
 information has 
been provided.
Treatment information for the 
 has been added.
Section 7.2, Treatment 
Administration and 
Schedule
•
Included additional 
instructions about first 
introduction of 
 presentation 
 
. 
Further, requirements for a 
First 
 Administration Visit 
are noted.
•
Additionally, text is included 
to clarify that if IP is not 
available on site at the time of 
Protocol Amendment 5 site 
approval, then subjects should 
continue receiving the single 
2.0 mL weekly SC injection 
using the 360 mg/2 mL PFS 
presentation, until the 
availability of the new IP (
 
presentation. 
•
To provide clarification as
to which assessments will 
be conducted in the First 
 Administration Visit.
•
To provide clarification on
which IP presentation 
should be provided to 
subjects.
Section 8.2, Prohibited 
Concomitant 
Medications and 
Procedures
•
Included JAK inhibitors 
andphosphodiesterase-4 
inhibitors as examples of 
immunomodulating drugs and 
as prohibited concomitant 
medications on study.
•
Added language to clarify that 
corticosteroids can be used for 
an EGE flare, or used for an 
adverse event (AE) with 
consultation with the Medical 
Monitor, and will not result in 
For clarification purposes.
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Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 5.0
Section Number & 
Title
Description of Change
Brief Rationale
permanent discontinuation of 
IP.
Section 9.1, Overview
Added details for database lock 
and clinical study report.
For clarification purposes.
Section 9.2, Study 
Population Definitions
Section 9.6.1.2,
Changes in Mean 
Number of Peak eos 
Count from Baseline to 
Week 16 (Induction 
Phase)
Section 9.6.3.1, 
Analyses Methods
Removed the Per-protocol (PP) 
population.
The PP population was 
removed as the specified 
estimands better address the 
objectives, and the PP 
population would not add 
additional insights.
Section 9.7, Safety 
Analysis
Updated information based on the 
 administration has been added.
Updated per changes in 
Protocol Amendment 5.
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.
Clarified that AESIs must be 
entered into EDC.
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 the IP.
For clarification purposes.
All 
Minor formatting and 
typographical corrections.
Minor edits that do not change 
the content of the protocol 
were made to improve 
readability and consistency.
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Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
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PROTOCOL SUMMARY
Study Title
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Induction and 
Maintenance Study to Evaluate the Efficacy and Safety of CC-93538 in Adult and Adolescent 
Japanese Subjects with Eosinophilic Gastroenteritis 
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 (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 gastrointestinal disorders (EGIDs) are a series of diseases that selectively affect the 
segments of gastrointestinal (GI) tract with eosinophilic inflammation in the absence of secondary 
causes for eosinophilia. These disorders can be divided into 2 principal groups: eosinophilic 
esophagitis (EoE) and eosinophilic gastroenteritis (EGE) for infants to adults (Rothenberg, 2004; 
Japan Intractable Diseases Information Center, 2021). They are considered to be caused by chronic 
allergic reactions to various allergens, including food and environmental antigens (Kinoshita, 
2019). Eosinophilic gastroenteritis is associated with inflammation of the stomach and large 
intestine, with abdominal pain, nausea, diarrhea, and malnutrition being the main symptoms. 
Recurrence occurs repeatedly in about 60% of patients, and the disease becomes chronic and 
steroid-dependent, causing various adverse reactions associated with drug therapy. In Japan, there 
have been many case reports of EGE, but there are few cases of EoE. In contrast, EoE is more 
common and EGE is less common in Europe and the United States. The prevalence of EGE in 
Japan is unknown, but EGIDs is estimated to be present in approximately 5000 patients. The
number of EGE patients is also unknown but has been estimated as 500 in 2010 (Japan Intractable 
Diseases Information Center, 2021). Although not approved in Japan, the most widely used 
treatment for EGE is systemic glucocorticoid administration. Prednisolone 20 to 40 mg/day is 
often orally administered, but there is no clear guidance on the dose, rate of dose reduction, timing 
of discontinuation, treatment for refractory cases, and treatments for recurrence or relapse. 
Systemic glucocorticoid therapy is often associated with long-term steroid side effects such as 
diabetes, osteoporosis, and depression because it is difficult to achieve effective remission of 
inflammation (Japan Intractable Diseases Information Center, 2021).
Although eosinophils are normally present in the lamina propria except in the esophagus, the 
number of eosinophils along the GI tract is variable, and the highest concentrations are found in 
the cecum and appendix (Oh, 2008; Ko, 2014). Eosinophils are involved in the mucosal immune 
system of the GI tract and have a role in host defense for healthy individuals (Lucendo, 2008). The 
number of eosinophils is increased in the pathogenesis of numerous inflammatory processes, 
including parasitic infections and allergic diseases. Activated eosinophils produce and release
highly bioactive inflammatory mediators like eosinophil cationic protein (ECP) and major basic 
protein. These cationic proteins possessing ribonuclease and antiviral activity are cytotoxic to the 
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GI epithelium. This process can trigger degranulation of mast cells and release of cytokines (eg,
IL-1, IL-3, IL-4, IL-5, IL-13, transforming growth factors), chemokines (eg, eotaxin, Regulation 
upon Activation Normal T-cell Expressed and Secreted [RANTES]), lipid mediators (eg,
leukotrienes, platelet activating factor), and neuromediators (eg, substance P, vasoactive intestinal 
polypeptide) (Khan, 2005; Rankin, 2000; Hogan, 2004).
CC-93538 has a 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). CC-93538 binds an
IL-13 epitope, comprised of residues in helix A and helix D (Ying, 2010). This binding in turn
prevents IL-13 from binding to both IL-13Rα1 and IL-13Rα2 (Ying, 2010), where IL-13 may be
implicated in EGE pathogenesis (Pesek, 2020; Wechsler, 2018; Hershey, 2003; Fichtner-Feigl,
2006; Fichtner-Feigl, 2008).
Results of the Phase 2 Study, Study RPC02-201, conducted in 99 adult subjects with symptomatic 
EoE showed that administration of 180 mg and 360 mg subcutaneous injection (SC) once weekly 
of CC-93538 reduced mean esophageal eosinophil count (the primary endpoint) and improved 
other inflammatory and symptomatic parameters; improvements in dysphagia symptoms were 
observed with the 360 mg dose. The study also demonstrated the safety and tolerability of CC-
93538 and showed continued clinical, endoscopic, and histologic improvements in subjects treated 
with 360 mg SC for up to 68 weeks of treatment and suggested that treatment was potentially 
effective in both steroid refractory and non-steroid refractory populations. These data support the 
continued development of CC-93538 as a novel treatment for EoE. As well as EoE, IL-13 is the 
dominant Th2 cytokine in the pathogenesis of EGE and CC-93538 is expected to act by 
neutralizing IL-13 and inhibiting infiltration and accumulation of eosinophils to inflammatory sites.
Thus, the single pivotal Phase 3 Study in adult and adolescent subjects with EoE (Study CC-93538-
EE-001) is designed to confirm and extend the findings obtained from the positive Phase 2 study
(Study RPC02-201) with CC-93538.
In addition to the multicenter, multinational, 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 Open-label Extension Study (Study CC-
93538-EE-002), the Phase 3 program includes a multicenter, open-label study to evaluate the 
efficacy and safety of CC-93538 in adult and adolescent Japanese subjects with EGE (Study CC-
93538-EG-001). The study includes subjects who have an inadequate response with, lost response 
to, or were intolerant to standard therapies. In Japan, there is no approved drug indicated for EGIDs
(EoE/EGE) as of February 2021, and the main treatment is symptomatic treatment such as systemic 
glucocorticoid administration and diet therapy using an elimination diet. As unmet medical needs
exist for EGE, new therapies with an effective and favorable safety profile are required. The study 
will include an Induction Phase, Maintenance Phase and an Open-label Long-term Extension 
(OLE) Phase.
Objectives
The primary objective of the study is to assess the efficacy of CC-93538 versus placebo in 
obtaining histologic improvement based on tissue eosinophil (eos) count in EGE at Week 16.
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The secondary objectives are:
•
To assess the efficacy of CC-93538 versus placebo in reducing EGE-related symptoms at
Week 16
•
To assess the efficacy and the persistence of effect of CC-93538 versus placebo at 48 weeks
in:
−
Obtaining histologic improvement based on tissue eos count in EGE
−
Reducing EGE-related symptoms
•
To assess the persistence of effect of CC-93538 through administration of a less frequent
dosing regimen at 48 weeks in:
−
Obtaining histologic improvement based on tissue eos count in EGE
−
Reducing EGE-related symptoms
•
To evaluate the safety and tolerability of CC-93538 including characterization of the
immunogenicity profile
•
To evaluate the efficacy and the persistence of effect of CC-93538 versus placebo for 48 weeks
in reducing concomitant corticosteroid use
•
To evaluate the time to and frequency of EGE flare events and use of rescue therapy during
the study
•
To assess trough concentrations of CC-93538 in subjects with EGE
Study Endpoints (Primary and Key Secondary)
Primary Endpoint
•
Changes in mean number of peak eos per high-power field (hpf) in GI biopsies from baseline
to Week 16
Key Secondary Endpoints
•
Changes from baseline in each of 5 domain scores of the Izumo Scale
•
The proportion of responders defined as subjects who achieve both clinical and histologic
response
•
Safety and tolerability 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, physical examination abnormalities and the presence of anti-drug
antibodies, including neutralizing antibodies when warranted
Study Design
Study CC-93538-EG-001 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled 
induction and maintenance study to assess the efficacy and safety of CC-93538 in adult and 
adolescent subjects with EGE. The study will incorporate a 16-week Induction Phase followed by 
a 32-week Maintenance Phase and an OLE Phase for a minimum of 2 years, but may extend for a 
longer duration. 
2.0
Approved
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Approved
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Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
17
Following a 4-week Screening Period, subjects meeting all inclusion criteria and none of the 
exclusion criteria will be eligible for enrollment in the 16-week Induction Phase. Subjects (N = 
approximately 45) will be randomized (2:1) to receive CC-93538 360 mg subcutaneously (SC) 
once weekly or matching placebo, in a double-blind fashion for the 16 weeks of the Induction 
Phase. At the beginning of the Maintenance Phase, subjects who are randomized to receive CC-
93538 360 mg SC once weekly in the Induction Phase will be re-randomized (1:1) to CC-93538 
360 mg SC once weekly or CC-93538 360 mg SC once every other week, and subjects who are 
randomized to receive matching placebo in the Induction Phase will continue placebo in the 
Maintenance Phase. A double-blind fashion will be kept in the Maintenance Phase. Subjects will
be required to have weekly symptom scores of ≥ 4/15 for any of Gastric Pain Symptom domain, 
Stomach Heaviness Symptom domain, and /or Diarrhea Symptom domain as assessed by the 
patient-reported outcome (PRO) questionnaire (referred to as Izumo Scale) with electronic device
over the 2 consecutive weeks before the investigational product (IP) administration on Day 1 and
has histologic evidence of EGE with ≥ 30 eos/hpf in at least 5 hpf in the stomach and/or ≥30 
eos/hpf in at least 3 hpf in the duodenum; both assessments will be conducted while on stable 
concomitant corticosteroid therapy (up to 10 mg/day as prednisone). Peak gastric/duodenum eos 
count 
will 
be 
confirmed 
by 
a 
centrally 
read 
histological 
assessment 
of 
an 
esophagogastroduodenoscopy (EGD) specimen. Subjects weighing ≥ 30 kg will be enrolled in this 
study. Currently, there is no administration experience of CC-93538 360 mg once weekly in 
subjects weighing < 40 kg. Careful and close safety monitoring should be implemented for this 
population. For subjects weighing ≥ 30 kg and <40 kg, the first 3 weekly SC doses will be 
administered in the clinic with confirmation of concomitant medications and AEs, and those 
subjects will remain in the clinic for at least 1 hour following dosing for observation and be 
monitored every 2 weeks by the site staff by telephone (but not limited to telephone) between 
regularly scheduled visits until Week 16 (ie, Week 6 [Day 43 ± 3 days], Week 10 [Day 71 ± 3
days], and Week 14 [Day 99 ± 3 days]).
Treatment assignment at baseline will be stratified by (with/without) concomitant corticosteroid 
treatment at baseline (up to 10 mg/day as the equivalent of prednisone) to ensure an equal balance 
in the treatment arms. 
The dosage regimen of permitted anti-inflammatory therapy (including concomitant corticosteroid 
treatment at baseline; up to 10 mg/day as the equivalent of prednisone) must be kept stable until 
Week 16. 
After completion of Week 16 of the Induction Phase, subjects will be eligible to enter the 
Maintenance Phase if none of the conditions that would disqualify subjects from continuing have 
been met, including the need for endoscopic intervention or concomitant use of rescue therapy for 
a severe EGE flare.
If the reduction of EGE-related symptoms is observed at/after Week 16 (in the Maintenance 
Phase), the investigator should begin tapering the dosage regimen of concomitant corticosteroids 
treatment after Week 16. The dose reduction should be 2.5 mg/week (as the equivalent of 
prednisone). If the symptoms worsen after tapering of the dosage regimen of concomitant
corticosteroid treatment, the dose can be increased to the baseline dose in the Induction Phase.
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
18
Clinical laboratory tests, vital signs, physical examinations 
, 
pregnancy tests, EGD, clinical symptom assessment, subject-reported outcomes, serum CC-93538 
pharmacokinetic concentrations, serum antibodies to CC-93538 (to assess immunogenicity), 
concomitant medications, and AE/SAE assessments will be performed.
 
Subjects experiencing a severe EGE flare in the Induction Phase may continue to participate with 
concomitant rescue therapy as needed and will not be eligible to enter the Maintenance Phase but 
will be eligible to enter the OLE Phase following completion of Week 16 of the Induction Phase.
If the results of the gastric/duodenal eos count is required to determine the need for rescue therapy 
during the Induction Phase, the subject is to be discontinued from the study and will not be allowed 
to enter either Maintenance Phase or OLE. Subjects who complete Week 48 of the Maintenance 
Phase are eligible to enter the OLE Phase. During the Maintenance Phase, subjects experiencing a 
severe EGE flare that requires rescue therapy and/or experience worsening of EGE symptoms (for 
2 consecutive visits, 4 weeks apart) may also enter the OLE Phase during the Maintenance Phase. 
Following the Induction Phase, subjects not entering the Maintenance Phase or the OLE Phase will 
return for an Interim and a Final Safety Follow-up Visit at 8 and 16 weeks for the assessment of 
safety and clinical status, respectively, after final investigational product (IP) administration. 
Similarly, subjects completing the Maintenance Phase who do not participate in the OLE Phase 
will complete the Interim and Final Safety Follow-up Visits (at 8 and 16 weeks, respectively) after 
final IP administration. Subjects who discontinue the study prematurely will be asked to complete 
an Early Termination (ET) Visit and return for the 2 Safety Follow-up Visits.
During the OLE Phase, all subjects will be administered CC-93538 at a dose of 360 mg SC once 
weekly. Subjects may discontinue from the study at any time. Furthermore, subjects who 
demonstrate a persistent lack of improvement or worsening of EGE symptoms during the course 
of the study should be evaluated to determine if continuing the study treatment is appropriate . 
Subjects who discontinue the study at or after 2 years of participation (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 OLE Week 104 will complete an Early Termination Visit.
The study will be conducted in compliance with International Conference for Harmonisation (ICH) 
Good Clinical Practices (GCPs).
Study Population
The study population will consist of males and females aged 12 to 75 years (inclusive) with EGE. 
Approximately 45 adults (aged 18 to 75 years) and adolescents (aged 12 to 17 years) with a weight 
of ≥ 30 kg will be enrolled in the study.
Length of Study
The maximum duration of subject participation in the Screening Period, Induction and 
Maintenance Phases is approximately 72 weeks, including the Interim and the Final Safety Follow-
2.0
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Approved
1.0
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Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
19
up Visits. Subjects will participate for up to 4 weeks in the Screening Period (the screening EGD 
may be completed up to 8 weeks prior to Day 1), 16 weeks in the Induction Phase, and 32 weeks 
in the Maintenance Phase of the study. Subjects completing the Maintenance Phase who do not 
continue IP administration in the OLE Phase will complete the Interim and the Final Safety 
Follow-up Visits (at 8 and 16 weeks) after final IP administration.
Subjects entering the OLE Phase at Induction Phase Week 16, during the Maintenance Phase or at 
Maintenance Phase Week 48 will receive weekly doses of CC-93538 during the OLE Phase for a 
minimum of 2 years or as long as they continue to participate while the study is active, will 
complete an Early Termination Visit or an End of Treatment Visit within 2 weeks after the final 
dose, and complete the two Safety Follow-up Visits at 8 and 16 weeks after the final dose. Subjects 
may participate in the OLE Phase as early as 16 weeks after beginning enrollment in the Induction 
Phase or as late as following Week 48 of the Maintenance Phase. Individual subject participation 
in the OLE Phase may be a minimum of 2 years but may extend for a longer duration, provided 
the subject does not withdraw from the OLE Phase prior to Year 2 of the OLE. The terms “this 
study” in this protocol will automatically be replaced with “post-marketing clinical study” on and 
after the date of marketing approval in Japan.
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up (the Final Safety Follow-up Visit), or the date of receipt of the last data 
point from the last subject that is required for primary, secondary 
 analysis, as 
prespecified in the protocol, whichever is the later date.
Study Treatments
Subjects will be randomized 2:1 to the following treatment arms for the 16-week Induction Phase:
•
CC-93538 360 mg SC once weekly for 16 weeks
•
Matching placebo SC once weekly for 16 weeks
Subjects who are randomized to receive CC-93538 360 mg SC once weekly in the Induction Phase
will be re-randomized 1:1 to the following treatment arms for the 32-week Maintenance Phase:
•
CC-93538 360 mg SC once weekly for 32 weeks
•
CC-93538 360 mg SC once every other week for 32 weeks. During the Maintenance Phase,
matching placebo will be administered once every other week on alternate weeks to maintain
the blind.
Subjects who are randomized to receive matching placebo in the Induction Phase will continue the 
following treatment arm.
•
Matching placebo SC once weekly for 32 weeks
The CC-93538 360 mg SC dose will be administered by 2 injections of 1.2 mL each provided in 
150 mg/mL pre-filled syringes (PFS) during the Induction Phase and the Maintenance Phase.
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
20
Subjects entering the OLE Phase will receive the following treatment:
•
CC-93538 360 mg SC once weekly during the OLE treatment period
For the OLE Phase, all subjects will receive CC-93538 360 mg SC once weekly during the OLE 
Phase. The 360 mg dose of CC-93538 will be administered by a single injection of the 360 mg/2
mL 
 at a concentration of 180 mg/mL CC-93538. All subjects currently in the 
OLE Phase will start receiving a single injection of the 360 mg/2 mL
 once Protocol Amendment 
5 is implemented, informed consent is obtained, and IP is available on-site.  For currently enrolled 
subjects, a switch to the new 
 presentation will occur at the next regularly scheduled study visit 
or at a First 
 Administration Visit in case the next scheduled protocol visit is not within 4 weeks 
of Protocol Amendment 5 site approval, once the IP is available on site. This First 
 
Administration Visit is added to expedite the switch to the new 
 presentation.
The dosing regimen for the OLE may be revised, via an amendment to the protocol, after results 
from the core Induction Phase and Maintenance Phase are available and the most effective and 
safest dosing regimen is confirmed.
Overview of Key Efficacy Assessments
•
Enumeration of gastric and/or duodenal eos count (peak gastric and/or duodenal eos count) by 
analysis of hematoxylin and eosin (H&E) stained gastric and/or duodenal biopsies
•
Gastrointestinal symptom score using the PRO questionnaire (Izumo Scale)
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 consequences of anti-drug antibodies (ADAs)
Statistical Methods
The primary population for assessing efficacy will be the intent-to-treat (ITT) population which
consists of all randomized subjects regardless of whether or not the subject received IP (CC-93538 
or placebo).
Analysis details not explained in the statistical section of the protocol will be provided in the 
Statistical Analysis Plan (SAP).
Sample Size
The sample size is based on two-sample t-test for the primary endpoint, changes in mean number 
of peak eos per hpf in GI biopsies from baseline to Week 16. The null hypothesis and the 
alternative hypothesis for the primary endpoint are as follows;
•
Changes in mean number of peak eos from baseline at Week 16
Null hypothesis H0: μCC-93538 = μPlacebo
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
21
Alternative hypothesis Ha: μCC-93538 ≠ μPlacebo,
where μCC-93538 represents the true mean change value relative to CC-93538 and μPlacebo represents
true mean change value relative to placebo.
Using this hypothesis, if the expected mean change in eos count in the active treatment group was 
-70, the expected mean change in eos count in the placebo group was 0, and the standard deviation
(SD) was 70, the sample size necessary to achieve at least 80% power in a t-test at a significance
level of 0.05 was calculated. Using a 2:1 ratio of active to placebo, 39 subjects are required.
Assuming a Week 16 drop-out rate of approximately 10%, the goal is to enroll a total of 45
subjects.
Primary Analysis
The primary analysis will be conducted on the ITT population based on an analysis of covariance 
(ANCOVA) model with treatment group, concomitant steroid use (yes or no), and baseline 
eosinophil count included in the model. The comparison between CC-93538 360 mg SC once 
weekly and placebo for change in eos count from baseline at Week 16 will be made using the 
difference in least squares mean (LSM) at a 5% 2-sided significance level. Point estimates for the 
mean difference between the two treatment groups using the LSM changes and corresponding 95% 
Wald confidence intervals (CI) will be reported. In addition, LSM (standard error [SE]), arithmetic 
means (SD), and arithmetic mean changes (SD) will be summarized by treatment group.
Multiplicity Adjustment
Only one formal statistical test will be performed for the primary endpoint. For any other 
comparisons, nominal p-value (without adjustment for multiplicity) will be provided as a measure 
of the strength of association between the endpoint and the treatment effect rather than a formal 
statistical test. Therefore, the multiplicity adjustment is not applicable in this study.
Safety Population
The safety population will consist of all subjects who received at least one dose of IP. The 
assessment of safety 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. Safety data will be summarized by treatment 
group using descriptive statistics.
Overall safety and tolerability will also be summarized for each drug presentation : the 360 mg 
dose of CC-93538 administered by two injections of 1.2 mL each at a concentration of 150 mg/mL 
CC-93538, or by one injection of 2.0 mL at a concentration of 180 mg/mL CC-93538 administered
with the PFS device, or by one injection of 2 mL at a concentration of 180 mg/mLCC-93538
administered with the 
 device utilizing descriptive statistics.
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 EGE and a statistician, 
all of whom are not otherwise involved in the study conduct and for whom there is no identified 
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
22
conflict of interest. During the study, the DMC will review selected data (to be specified in the 
DMC charter) on a regular basis for the assessment of benefit-risk and determination of study 
continuation. An independent third party will prepare the reports of aggregate data summaries and 
individual subject data listings, as appropriate, for the DMC members for each scheduled meeting.
Operational details for the DMC, including a blinding plan to assure that all personnel involved in 
the conduct of the study remain blinded to the results of data reviews, will also be described in the 
DMC charter.
2.0
Approved
930196221
2.0
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Approved
1.0
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Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
23
TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 5.0:............................................7
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 5.0.........................................7
PROTOCOL SUMMARY ........................................................................................................14
TABLE OF CONTENTS..........................................................................................................23
LIST OF TABLES....................................................................................................................28
LIST OF FIGURES ..................................................................................................................29
1
INTRODUCTION..................................................................................................30
1.1
Disease Background ...............................................................................................30
1.1.1
Pathophysiology .....................................................................................................30
1.1.2
Symptoms and Diagnosis ........................................................................................31
1.1.3
Current Available Therapies and Standard of Care ................................................32
1.2
Compound Background ..........................................................................................33
1.2.1
Mechanism of Action ..............................................................................................33
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..........................................................................35
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.....................................................................................37
1.3
Rationale ................................................................................................................38
1.3.1
Study Rationale and Purpose..................................................................................38
1.3.2
Rationale for the Study Design................................................................................38
1.3.2.1
Benefit-Risk Assessment..........................................................................................39
1.3.3
Rationale for Dose, Schedule and Regimen Selection..............................................40
1.3.3.1
Justification of Primary Endpoints..........................................................................40
1.3.4
Rationale for Choice of Comparator Compounds ...................................................41
41
2
STUDY OBJECTIVES AND ENDPOINTS...........................................................42
3
OVERALL STUDY DESIGN ................................................................................52
3.1
Study Design ..........................................................................................................52
3.1.1
Screening Period ....................................................................................................53
3.1.2
Induction Phase......................................................................................................53
3.1.3
Maintenance Phase.................................................................................................54
3.1.4
Open-label Long-term Extension Phase..................................................................55
3.1.5
Early Termination, End of Treatment and Safety Follow-up Visits ..........................56
3.1.6
Worsening of EGE Symptoms and EGE flare..........................................................57
3.2
Study Duration for Subjects....................................................................................58
3.3
End of Trial ............................................................................................................59
4
STUDY POPULATION.........................................................................................60
4.1
Number of Subjects ................................................................................................60
4.2
Inclusion Criteria....................................................................................................60
4.3
Exclusion Criteria...................................................................................................62
2.0
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2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
24
5
TABLES OF EVENTS...........................................................................................65
6
PROCEDURES......................................................................................................84
6.1
Screening Period.....................................................................................................85
6.1.1
Additional Information Regarding Safety Laboratory Assessments .........................88
6.1.2
Screening Failures and Rescreening of Potential Subjects ......................................88
6.1.2.1
Retesting of Subjects who Develop COVID-19 During the Screening Period...........89
6.2
Induction Phase and Maintenance Phase.................................................................89
6.2.1
EGE Flare Assessment Visit....................................................................................92
6.2.2
Early Termination Visit ..........................................................................................93
6.3
Follow-up Period....................................................................................................95
6.3.1
Safety Follow-up (Interim 8-week and Final 16-week) ............................................95
6.3.2
Open-label Long-term Extension (OLE) Phase .......................................................96
.99
6.3.2.2
OLE - Early Termination Visit/End of Treatment: Visit...........................................99
6.4
Efficacy Assessment.............................................................................................101
6.4.1
Esophagogastroduodenoscopy (EGD) ..................................................................101
6.4.2
Clinical Symptoms of EGE....................................................................................102
6.4.2.1
Izumo Scale Questionnaire...................................................................................102
6.4.2.2
EGID Severity Score.............................................................................................104
104
105
105
105
106
106
106
6.4.2.10
Worsening of EGE Symptoms, EGE Flare, and the EGE Flare Assessment 
Visit......................................................................................................................107
6.4.2.11
Entry to Maintenance Phase .................................................................................108
6.4.2.12
Entry to Open-label Long-term Extension.............................................................109
6.5
Anti-drug Antibody Assessments..........................................................................109
6.6
Pharmacokinetics..................................................................................................109
6.6.1
Serum CC-93538 Assessments ..............................................................................109
110
110
110
110
110
111
111
111
111
112
7
DESCRIPTION OF STUDY TREATMENTS......................................................113
7.1
Description of Investigational Product(s)..............................................................113
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CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
25
7.2
Treatment Administration and Schedule ...............................................................114
7.2.1
Induction Phase....................................................................................................114
7.2.2
Maintenance Phase...............................................................................................114
7.2.3
OLE Phase ...........................................................................................................114
7.2.4
Post Injection Observation....................................................................................115
7.2.5
Instructions for IP Administration.........................................................................116
7.2.6
Self-Administration...............................................................................................116
7.2.7
Missed Dose(s) .....................................................................................................117
7.2.8
Dose Adjustments .................................................................................................117
7.2.9
Guidelines for Temporary Interruption of Dosing.................................................117
7.2.10
Criteria for Discontinuation of Dosing .................................................................118
7.2.11
Rescue Therapy ....................................................................................................118
7.3
Method of Treatment Assignment.........................................................................119
7.3.1
The Induction Phase and the Maintenance Phase .................................................119
7.3.2
The OLE Phase.....................................................................................................119
7.4
Packaging and Labeling........................................................................................119
7.4.1
The Induction Phase and the Maintenance Phase .................................................119
7.4.2
The OLE Phase.....................................................................................................120
7.5
Investigational Product Accountability and Disposal ............................................120
7.6
Investigational Product Compliance......................................................................120
8
CONCOMITANT MEDICATIONS AND PROCEDURES..................................121
8.1
Permitted Concomitant Medications and Procedures.............................................121
8.1.1
Rescue Therapy ....................................................................................................122
8.2
Prohibited Concomitant Medications and Procedures............................................122
8.3
Required Concomitant Medications and Procedures..............................................126
9
STATISTICAL CONSIDERATIONS ..................................................................127
9.1
Overview..............................................................................................................127
9.2
Study Population Definitions ................................................................................127
9.3
Sample Size and Power Considerations.................................................................127
9.4
Background and Demographic Characteristics......................................................128
9.5
Subject Disposition...............................................................................................128
9.6
Efficacy Analysis..................................................................................................129
9.6.1
Efficacy Analysis of the Primary Endpoint............................................................129
9.6.1.1
Intercurrent Event and Analysis Strategies ...........................................................129
9.6.1.2
Changes in Mean Number of Peak eos Count from Baseline to Week 16 
(Induction Phase) .................................................................................................129
9.6.2
Subgroup Analyses ...............................................................................................129
9.6.3
Analysis of Secondary Efficacy Endpoints.............................................................130
9.6.3.1
Analyses Methods .................................................................................................130
9.7
Safety Analysis.....................................................................................................131
9.8
Interim Analysis ...................................................................................................132
9.9
Other Topics.........................................................................................................132
9.9.1
Pharmacokinetics, 
...........................132
132
9.9.3
Internal Safety Management Team........................................................................133
9.9.4
External Data Monitoring Committee...................................................................133
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CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
26
10
ADVERSE EVENTS............................................................................................134
10.1
Monitoring, Recording and Reporting of Adverse Events .....................................134
10.2
Evaluation of Adverse Events...............................................................................135
10.2.1
Seriousness...........................................................................................................135
10.2.2
Severity/Intensity ..................................................................................................136
10.2.3
Causality ..............................................................................................................137
10.2.4
Duration...............................................................................................................137
10.2.5
Action Taken.........................................................................................................137
10.2.6
Outcome ...............................................................................................................137
10.3
Abnormal Laboratory Values................................................................................137
10.4
Pregnancy.............................................................................................................138
10.4.1
Females of Childbearing Potential .......................................................................138
10.5
Reporting of Serious Adverse Events....................................................................139
10.5.1
Safety Queries ......................................................................................................139
10.6
Adverse Events of Special Interest........................................................................139
10.7
Expedited Reporting of Adverse Events................................................................140
11
DISCONTINUATIONS .......................................................................................141
11.1
Treatment Discontinuation....................................................................................141
11.2
Study Discontinuation ..........................................................................................142
11.3
Emergency Contact...............................................................................................143
11.4
Emergency Identification of Investigational Products ...........................................144
12
REGULATORY CONSIDERATIONS.................................................................145
12.1
Good Clinical Practice..........................................................................................145
12.2
Investigator Responsibilities .................................................................................145
12.3
Subject Information and Informed Consent...........................................................146
12.4
Confidentiality......................................................................................................146
12.5
Protocol Amendments...........................................................................................146
12.6
Institutional Review Board/Independent Ethics Committee Review and 
Approval ..............................................................................................................146
12.7
Ongoing Information for Institutional Review Board/Ethics Committee ...............147
12.8
Termination of the Study ......................................................................................147
13
DATA HANDLING AND RECORDKEEPING...................................................149
13.1
Data/Documents ...................................................................................................149
13.2
Data Management.................................................................................................149
13.3
Record Retention..................................................................................................149
14
QUALITY CONTROL AND QUALITY ASSURANCE......................................151
14.1
Study Monitoring and Source Data Verification....................................................151
14.2
Audits and Inspections..........................................................................................151
14.3
Investigational Medicinal Product Quality Issues..................................................151
15
PUBLICATIONS .................................................................................................153
16
REFERENCES.....................................................................................................154
APPENDIX A
TABLE OF ABBREVIATIONS...........................................................160
APPENDIX B
IZUMO SCALE ...................................................................................165
APPENDIX C
EGID SEVERITY SCORE (FOR AGES ≥ 20 YEARS OLD) ..............167
APPENDIX D
EGID SEVERITY SCORE (FOR AGES FROM 2 TO 19 YEARS 
OLD)....................................................................................................169
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171
APPENDIX F
PROTOCOL AMENDMENT SUMMARY OF CHANGE 
HISTORY ............................................................................................172
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LIST OF TABLES
Table 1:
Study Objectives ....................................................................................42
Table 2:
Study Endpoints: Induction and Maintenance Phase Endpoints 
Through Week 48...................................................................................44
Table 3:
Study Endpoints: Open-label Long-term Extension Period 
Endpoints After Week 48 .......................................................................48
Table 4:
Table of Events for the Induction Phase..................................................65
Table 5:
Table of Events for the Maintenance Phase.............................................72
Table 6:
Table of Events for the Open-label Long-term Extension (OLE).............77
Table 7:
Medications, Diets, or Procedures Requiring Stable Dosing 
Regimens or Restricted Use Prior to Study Enrollment.........................124
Table 8:
Abbreviations and Specialist Terms......................................................160
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LIST OF FIGURES
Figure 1:
Overall Study Schema ............................................................................52
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1
INTRODUCTION 
1.1
Disease Background 
Eosinophilic gastrointestinal disorders (EGIDs) are a series of diseases that selectively affect the 
segments of the gastrointestinal (GI) tract with eosinophilic inflammation in the absence of 
secondary causes for eosinophilia. These disorders can be divided into 2 principal groups: 
eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE) for infants to adults 
including the elderly (Rothenberg, 2004; Japan Intractable Diseases Information Center, 2021). 
Eosinophilic esophagitis is characterized by inflammation in the esophagus, and causes symptoms 
such as difficulty in swallowing and a feeling of choking, which interfere with activities of daily 
living due to dysphagia. In long-term cases, it may cause esophageal fibrosis and stenosis. 
Eosinophilic gastroenteritis is associated with inflammation of the GI tract from the esophagus / 
stomach to the large intestine, with abdominal pain, nausea, diarrhea, and malnutrition being the 
major symptoms. Recurrence occurs repeatedly in about 60% of patients, and the disease becomes 
chronic and steroid-dependent, causing various adverse reactions associated with drug therapy. In 
Japan, there have been many case reports of EGE, but there are few cases of EoE. In contrast, EoE 
is more common and EGE is less common in Europe and the United States (US). The prevalence 
of EGE in Japan is unknown, but EGIDs are estimated to be present in approximately 5000 
patients. The number of EGE patients is also unknown but has been estimated as 500 in 2010 
(Japan Intractable Diseases Information Center, 2021). The exact prevalence of EGIDs in the US 
is unknown, but the estimated prevalence of EoE is reported as 56.7/100,000 (Dellon, 2014) and 
that of EGE is 14.7/100,000 (Jensen, 2016). The prevalence of EGIDs in the US/European Union
has been increasing in recent years, and a similar finding has been reported in Japan (Fujishiro, 
2011; Kinoshita, 2015; Chehade, 2021). Although eosinophils (eos) are normally present in the 
lamina propria except the esophagus under noninflammatory conditions, the number of eos along 
the GI tract is variable, and the highest concentrations are found in the cecum and appendix (Oh, 
2008; Ko, 2014). They are involved in the mucosal immune system of the GI tract and have a role 
in host defense for healthy individuals (Lucendo, 2008). The number of eos increases in the 
pathogenesis of numerous inflammatory processes, including parasitic infections and allergic 
diseases. In these states activated eos produce and release highly bioactive inflammatory mediators 
like eosinophil cationic protein (ECP) and major basic protein. These cationic proteins possessing 
ribonuclease and antiviral activity are cytotoxic to the GI epithelium. This could trigger 
degranulation of mast cells and release of cytokines (eg, interleukin (IL)-1, IL-3, IL-4, IL-5, IL-
13, transforming growth factors), chemokines (eg, eotaxin, Regulation upon Activation Normal T-
cell Expressed and Secreted [RANTES]), lipid mediators (eg, leukotrienes, platelet activating 
factor), and neuromediators (eg, substance P, vasoactive intestinal polypeptide) (Khan, 2005; 
Rankin, 2000; Hogan, 2004).
1.1.1
Pathophysiology
Eosinophilic gastroenteritis is an uncommon and heterogeneous disease characterized by 
eosinophilic infiltration of the GI tract and the inflammatory process may involve the entire GI 
tract, presenting with a variety of GI manifestations that depend on the site affected and the layer 
of the GI wall involved (Klein, 1970). Additionally, many patients may have a concomitant history 
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of atopic conditions including asthma, allergic rhinitis or atopic dermatitis, as well as allergy to 
medicine, food, or pollen (Reed, 2015; Ko, 2014).
The pathogenesis of EGE is thought to be similar to that of EoE and may be due to abnormal 
immune responses leading to increased eos counts and inflammation in the GI tract, though the 
details of this immunological abnormality have yet to be fully clarified. Indeed, several basic and 
clinical similarities between EoE and EGE have been demonstrated (Kinoshita, 2013; Furuta, 
2013; Ishimura, 2013; Kinoshita, 2012; Ishihara, 2017; Caldwell, 2014; Shoda, 2016). Microarray 
analyses of both EGE and EoE have shown similar findings of increased T-helper type 2 (Th2)
responses in the GI mucosa. Furthermore, co-occurrence of esophageal and GI eos infiltration is 
not a rare condition and suggests a similar pathogenesis for both. Based on their similarities, EGE 
is thought to be a chronic Th2-type eos allergic reaction caused mainly by food allergens, such as 
also seen with EoE (Sato, 2017; Kinoshita, 2019; Sekai, 2021). Additionally, to support this 
knowledge, the improvement of dysphagia symptoms in patients with concomitant EoE has been 
reported in a clinical study of another drug in patients with EGE (Dellon, 2020; Hirano, 2020).
1.1.2
Symptoms and Diagnosis
Compared to EoE, which is localized to the esophagus, EGE is a disease that affects the entire GI 
tract and its symptoms differ depending on the location of the lesion. Symptoms of EGE are non-
specific and various, and include abdominal pain, nausea, vomiting, early satiety, loss of appetite, 
abdominal cramping, bloating, and diarrhea. Abdominal pain and nausea are the most frequent 
presenting main symptoms in children and adults. Bleeding, anemia, protein-losing enteropathy, 
malabsorption, and weight loss are also observed. Gastrointestinal obstruction, intestinal rupture, 
peritonitis and eosinophilic ascites may occur in severe cases. As unusual complications of EGE, 
pancreatitis, acute bowel obstruction, duodenal ulcer or perforation have also reported (Reed, 
2015; Pineton, 2011; Ko, 2014; Zhang, 2011; Zhang, 2017; Kinoshita, 2013; Kant, 2021; Japan 
Intractable Diseases Information Center, 2021).
The natural history of EGE remains largely unknown. Three different patterns of disease course 
are reported: (1) a single flare of EGE, defined by GI symptoms present for less than 6 months 
associated with the absence of any relapse after initial flare; (2) a recurring course of EGE, defined 
by at least two flares of the disease separated by a period without GI symptoms and without 
peripheral blood eosinophilia; (3) a chronic continuous course of the disease, defined by chronic 
persistent GI symptoms for more than 6 months without period of remission. It was also found that 
absence of spontaneous remission and high blood eos count at diagnosis was significantly 
associated with a high risk of clinical relapse (Zhang, 2017). It has also been reported that 
approximately 40% of patients with EGE are cured without relapse, while approximately 50% of 
patients develop recurrence and chronic persistent GI symptoms (Pineton, 2011).
In Japan, the Japan Ministry of Health, Labour and Welfare (MHLW) proposed the diagnostic 
criteria of EGE in “Guidelines for diagnosis and treatment of eosinophilic gastroenteritis (draft)” 
in 2011 (Kinoshita, 2017; Japan Intractable Diseases Information Center, 2021) as follow;
Subjects who meet criteria 1 and 2, or 1 and 3, will be diagnosed as EGE.
1. The presence of GI symptoms (abdominal pain, diarrhea, vomiting, etc.)
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2. The presence of infiltration of inflammatory cells mainly consisting of eos in the mucosa
shown in biopsies of the stomach, small intestine, and large intestine (eosinophilic infiltration: ≥
20 cells/high power field (hpf), biopsy should be performed at several sites, and other
inflammatory bowel diseases should be ruled out)
3. The presence of ascites, with numerous eos in the ascites
The following are used as additional diagnostic criteria as reference: a history of allergic disease
such as asthma, the confirmation of eosinophilia in peripheral blood, the confirmation of
thickening of the wall of the stomach and intestinal tract shown by computed tomography scan,
the confirmation of edema, redness, and erosion in the stomach, small intestine, and large intestine
shown by endoscopy, and/or effectiveness of glucocorticoid therapy.
1.1.3
Current Available Therapies and Standard of Care
The most widely used treatment for EGE is systemic glucocorticoid administration, but it is not 
approved in Japan. Prednisolone 20 to 40 mg/day is often orally administered, but there is no clear 
guidance on the dose, rate of dose reduction, timing of discontinuation, treatment for refractory 
cases, and treatments for recurrence or relapse. Systemic glucocorticoid therapy is often associated 
with long-term steroid side effects such as diabetes, osteoporosis, and depression because it is 
difficult to achieve effective remission of inflammation (Japan Intractable Diseases Information 
Center, 2021). Although the value of antiallergic drugs has been investigated, none of the findings 
obtained showed adequate effectiveness. In consideration of the disease pathogenesis, use of an 
elimination diet has been investigated and the effects reported in a case report and case series, with 
some limitations (Ko, 2014; Lucendo, 2015; Yamada, 2014).
In Japan, there is no approved drug indicated for EGIDs (EoE/EGE) as of July 2023, and the main 
treatment is symptomatic treatment such as systemic glucocorticoid administration and diet 
therapy using an elimination diet. 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 cosignaling 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). As there is still no approved drug indicated for EGE and 
unmet medical needs exist, new therapies with an effective and favorable safety profile are 
required.
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1.2
Compound Background 
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. The fragment, crystallizable 
(Fc) region of CC-93538 is mutated at residues L240A and L241A in the heavy chain hinge/CH2 
region 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 
a 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). CC-93538 binds an IL-13 epitope, 
comprised of residues in helix A and helix D (Ying, 2010). This binding in turn prevents IL-13 
from binding to both IL-13Rα1 and IL-13Rα2 (Ying, 2010), where IL-13 may be implicated in 
EGE pathogenesis (Pesek, 2020; Wechsler, 2018; 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. Two 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. The 
details are described in the Investigator’s Brochure.
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 
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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 
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 a Phase 2, multicenter, global, randomized, double-blind, placebo-
controlled, parallel-group study to evaluate the safety and efficacy of CC-93538 in adult subjects 
with moderate-to-severe 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 this protocol amendment.
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 144 hours (approximately 6 days). CC-93538 showed a long
t½ of approximately 475 to 497 hours (approximately 20 to 21 days) and a small volume of
distribution of approximately 5 L. The SC bioavailability of CC-93538 was estimated to be
approximately 53%. Anti-CC-93538 antibodies were detected in 10 of 24 subjects. Of those 10
subjects, 3 had pre-existing antibodies and there was no indication that the response increased after
treatment. Thus, in 7 out of 24 (29%) subjects, treatment-induced ADAs were detected. Of those
7 subjects for which treatment-induced ADAs were detected, the ADA titers were low for 6 of
them. However, 1 subject had titers that were higher than the others (20- to 50-fold). Despite this,
there was no indication that exposure was impacted in that subject or in any of the subjects who
had treatment-induced ADAs. 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 
headache and viral infection. 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.
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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. 
Preliminary results show that following SC administration of either 180 mg or 360 mg CC-93538, 
the absorption of CC-93538 was slow with a median tmax of 5.4 to 7.5 days. A long 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% confidence interval (CI) for the least squares geometric mean ratios for 
Cmax and AUC from a combined dose analysis were found to be approximately within the typical 
80% to 125% range. 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 a 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 upper respiratory tract infection, 
cough, back pain, headache, and anemia. 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 (2 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 2 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 2 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. 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 
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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) (3 subjects from 
the 150 mg/mL treatment group and one subject from the 180 mg/mL treatment group). 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 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 
 versus PFS, and to 
evaluate the PK of CC-93538 when administered by the 
 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 
 in the abdomen. In Part 2 of the study, 
40 subjects were randomized 1:1 to receive CC-93538 360 mg SC by 
 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 
 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 
 were contained entirely within 80% to 125%, indicating the 2 devices (PFS and 
 
are biocomparable.
In Part 2, cendakimab exposure when administered using 
 in upper arm or upper thigh was ~20% 
higher than that in abdomen. The differences were not expected to be clinically meaningful. The 
cendakimab exposure between upper arm and upper thigh administration were comparable.
In Part A, 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 
 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 
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Anti-drug antibodies (ADAs) were detected in 10 subjects (4 in the PFS arm and 6 in the 
 arm 
[1 subject in the 
 arm had existing ADAs at baseline]). ADA profiles were similar between 
subjects receiving CC-93538 with the PFS or 
 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 
The two presentations of CC-93538, given by PFS or 
 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 
subjects with EoE (Hirano, 2019). Subjects weighing ≥ 40 kg and ≤ 125 kg with EoE have shown 
an initial IV loading dose of CC-93538 followed by administration of 180 mg or 360 mg SC 
weekly reduced mean esophageal eos count and improved other inflammatory parameters (see the 
Investigator’s Brochure). In the primary efficacy endpoint analysis, the mean changes from 
baseline to Week 16 in mean esophageal eos count measured in the 5 most inflamed 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).
Additionally, CC-93538 360 mg SC ameliorated dysphagia symptoms. In the open-label long-term 
extension, treatment of subjects with the weekly 360 mg SC dose demonstrated improvements in 
subjects who transitioned from placebo and sustained effect in those who originally received the 
180 mg or 360 mg dose in the controlled period of the study. The mean change from baseline to 
Week 16 in the dysphagia clinical symptom frequency and severity score (also referred to as the 
Dysphagia Symptom Diary [DSD] composite score), as assessed by the DSD instrument over the 
prior 2 weeks was -6.41, -5.31, and -13.31 in the Placebo, CC-93538 180 mg, and CC-93538 
360 mg groups, respectively. No IV loading dose was used in those subjects who entered the open-
label extension. The study also demonstrated the safety and tolerability of CC-93538 and showed 
continued clinical, endoscopic, and histologic improvements in subjects treated with 360 mg SC 
for up to 68 weeks of treatment and suggested that treatment was potentially effective in both 
steroid refractory and non-steroid refractory populations. These Phase 2 data indicate that targeting 
IL-13 with CC-93538 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 treatment for EoE.
As well as EoE, IL-13 is the dominant Th2 cytokine in the pathogenesis of EGE and CC-93538 is 
expected to act by neutralizing IL-13 and inhibiting infiltration and accumulation of eos to 
inflammatory sites.
Please refer to the investigator’s Brochure for detailed information concerning the available 
pharmacology, toxicology, drug metabolism, clinical studies, and adverse event profile of the 
investigational product (IP).
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Protocol CC-93538-EG-001 Amendment 5.0
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1.3
Rationale
1.3.1
Study Rationale and Purpose
In Japan, EGE together with EoE is considered as an intractable disease designated as EGIDs
(Intractable Diseases No.98). Based on opinions from medical experts of EGIDs, there is an 
extremely high unmet medical need for EGE in addition to EoE in Japan, and there is a strong 
desire for the development of new therapeutic drugs.
Given that the number of patients with EGE in other countries is smaller than that in Japan, and 
the development of CC-93538 is planned to prioritize EoE, no clinical study of EGE has been 
conducted and no multi-regional clinical trial is planned.
In consideration of the above situation, it was planned to conduct the Japan local Phase 3 study in 
patients with EGE (Study CC-93538-EG-001) in parallel with the global Phase 3 study in patients 
with EoE (Study CC-93538-EE-001) in order to meet the needs for treatment of EGE in clinical 
practice in Japan, and to develop the drug for the indication of EGIDs. As with EoE, EGE primarily 
involves eos infiltration into the GI tract, and CC-93538, an anti-IL-13 antibody, is expected to 
have an effect on both diseases with a similar mechanism of action.
No clinical studies of CC-93538 in patients with EGE have been conducted. However, 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 
(Study RPC02-201) of 99 adult subjects with EoE, weekly administration of CC-93538 360 mg 
SC reduced mean esophageal eos count and improved other inflammatory and symptomatic 
parameters. These results support the continued development of CC-93538 as a novel treatment 
for EoE. The single pivotal Phase 3 study is designed to confirm and extend the findings obtained 
from the positive Phase 2 study with CC-93538.
1.3.2
Rationale for the Study Design
The Phase 3 program includes a multicenter, Japan-local, randomized, double-blind, placebo-
controlled induction and maintenance study to evaluate the efficacy and safety of CC-93538 in 
adult and adolescent subjects with EGE (Study CC-93538-EG-001). In addition, 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
(Study CC-93538-EE-002) are included.
The EGE study includes a 16-week Induction Phase followed by a 32-week Maintenance Phase, 
and an Open-label Long-term Extension (OLE) Phase for a minimum of 2 years. A double-blind, 
placebo-controlled treat-through design with allowance for use of concomitant corticosteroid 
therapy and concomitant rescue therapy has been chosen, as it enhances subject recruitment and 
retainment for evaluation of relevant short-term as well as the long-term efficacy of CC-93538 in 
EGE. Since chronic administration of systemic steroids should be avoided as much as possible, 
the timing of the primary endpoint evaluation was set at 16 weeks, taking into account the timing 
at which the dosage of systemic steroids can be changed.
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Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
39
For the OLE Phase, the CC-93538 360 mg SC dose will be administered by a single injection of 2 
mL provided in a 360 mg/2 mL 
in Protocol Amendment 5. The results of Study CC-93538-CP-
002 support the introduction of the new 360 mg/2.0 mL PFS presentation administered as a single 
injection in Protocol Amendment 4 (see Section 1.2.2.5). Further, Study IM042-003 Part 1 
preliminary results demonstrated that the 
 presentation was biocomparable to the PFS 
presentation. The two presentations of CC-93538, given by PFS or 
 administered as a single 
dose of 360 mg, were well tolerated and had an acceptable safety profile in healthy adults. The 
ADA profiles were similar between subjects receiving the CC-93538 with the PFS or 
 with no 
differences in safety, tolerability, or PK. The results of Study IM042-003 support the introduction 
of the 360 mg/2 mL 
 presentation in Protocol Amendment 5.
1.3.2.1
Benefit-Risk Assessment
As few treatment options exist for patients with EGE, there is an unmet need for new 
pharmacotherapies targeting the pathophysiology of EGE 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, EGE, and other inflammatory 
conditions. The overall safety profile of CC-93538 remains consistent with the information that 
has been presented in the Investigator's Brochure (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 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 assessments, 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 temporarily interrupting or permanently 
discontinuing IP (Section 7.2.9 and Section 7.2.10), and criteria for reinitiating IP on resolution of 
a COVID-19 infection (Section 7.2.9). 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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CC-93538 (BMS-986355)
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Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
40
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 specialized 
electronic case report form (eCRF) pages, 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, it may particularly affect individuals with underlying chronic diseases. Based 
on the available safety data with CC-93538, and the established safety profile of other biologic 
immunomodulators targeting the IL-13 pathway, the overall benefit-risk for participation in this 
EGE study with CC-93538 is considered favorable. The individual benefit-risk considerations 
regarding COVID-19 infection remain 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 is considered a simple concomitant medication within the study. 
However, the efficacy and safety of non-live vaccines (including non-live COVID-19 vaccines) in 
subjects receiving CC-93538 are unknown. If a participant has received a specific COVID-19 
vaccination, details such as type and date of vaccine received should be recorded on the COVID-
19 Vaccination Form.
1.3.3
Rationale for Dose, Schedule and Regimen Selection
In the Phase 2 EoE study (Study RPC02-201), two dose levels were evaluated: CC-93538 180 mg 
and 360 mg SC dosing administered every week. The study results demonstrated that the 360 mg 
dose was more effective on the clinical symptom endpoints, with a favorable safety profile. 
Therefore, the CC-93538 360 mg once weekly dose has been selected for Induction Phase (up to 
Week 24) of the Phase 3 EoE study (Study EE-001).
The pathogenesis of EGE is thought to be similar to that of EoE and may be due to abnormal 
immune responses leading to increased eosinophils counts and inflammation in the GI tract, though 
the details of this immunological abnormality have yet to be fully clarified. Since CC-93538 is 
expected to have similar effects in the process of eos accumulation in the GI mucosa in both EoE 
and EGE, the same dosage and administration methods as those used in Induction Phase of Study 
EE-001 (360 mg once weekly) were selected in the Induction Phase (up to Week 16) of the Phase 
3 EGE study (Study EG-001).
Since CC-93538 is expected to be used for a long duration for the management of EoE and EGE, 
Study EE-001 is designed to investigate whether the same effect can be maintained in the 
Maintenance Phase (After Week 24) at 360 mg once weekly and 360 mg once every 2 weeks. 
Also, 360 mg was to be administered once every 2 weeks in addition to once weekly in the 
Maintenance Phase (After Week 16) of Study EG-001.
1.3.3.1
Justification of Primary Endpoints
The selection of the primary endpoint, change in mean number of peak eos per hpf in GI biopsies 
from baseline to Week 16, is based on the following rationales:
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CC-93538 (BMS-986355)
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Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
41
•
The pathogenesis of EGE-containing EGIDs is clear and involves eos accumulation and
infiltration in the GI tract. Medical experts have commented that in clinical practice, treatment
of eosinophilic GI diseases should be performed based on the reduction of eos count at the
lesion site. Therefore, medical experts have also advised that the evaluation of histologic eos
count in GI tissues is meaningful and should be included as the primary endpoint of this study.
•
A decrease in eos count and improvement in clinical symptoms in EGE-containing EGIDs
patients were retrospectively investigated by Pesek et al. A report showed that a decrease in
eos in the GI tract correlated with improvement in clinical symptoms and endoscopic and
histological findings in 373 patients with EGIDs (EGE: 265 subjects, eosinophilic colitis: 108
subjects) (Pesek, 2019). Therefore, it is very likely that improvement of histological eos count
in the GI tract will lead to improvement of clinical symptoms. Evaluation of eos count in the
GI tract has clinical significance, and it is appropriate to set it as the primary endpoint of this
study.
•
Eosinophil count decreased was evaluated as the primary endpoint in both the Phase 2 study
of this drug in subjects with EoE and the Phase 2 study of another drug (AK002) in subjects
with EGE conducted in the US (Dellon, 2020). A statistically significant decrease in eos count
was observed in the active groups compared to placebo.
1.3.4
Rationale for Choice of Comparator Compounds
The study design employs a comparison to placebo which is intended to minimize bias and to 
provide an accurate determination of efficacy and safety findings attributable to CC-93538 
administration. In addition, there are currently no approved products for the treatment of EGE in 
Japan and no comparators available for subjects with EGE.
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Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
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2
STUDY OBJECTIVES AND ENDPOINTS
The objectives for this study are listed in Table 1, and the study endpoints are described in Table 2
for the Induction Phase and the Maintenance Phase and Table 3 for the OLE Phase.
Table 1:
Study Objectives
Primary Objective:
The primary objective of the study is to assess the efficacy of CC-93538 versus placebo in obtaining histologic 
improvement based on tissue eosinophils (eos) count at Week 16. 
Secondary Objective(s)
The secondary objectives are: 
•
To assess the efficacy of CC-93538 versus placebo in reducing eosinophilic gastroenteritis (EGE)-related 
symptoms at Week 16
•
To assess the efficacy and the persistence of effect of CC-93538 versus placebo at 48 weeks in:
−
Obtaining histologic improvement based on tissue eos count in EGE
−
Reducing EGE-related symptoms
•
To assess the persistence of effect of CC-93538 through administration of a less frequent dosing regimen at 
48 weeks in:
−
Obtaining histologic improvement based on tissue eos count in EGE
−
Reducing EGE-related symptoms
•
To evaluate the safety and tolerability of CC-93538 including characterization of the immunogenicity profile
throughout the study
•
To evaluate the efficacy and the persistence of effect of CC-93538 versus placebo for 48 weeks in reducing 
concomitant corticosteroid use
•
To evaluate the time to and frequency of EGE flare events and use of rescue therapy during the study
•
To assess trough concentrations of CC-93538 in subjects with EGE
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Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
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Table 1:
Study Objectives
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Table 2:
Study Endpoints: Induction and Maintenance Phase Endpoints 
Through Week 48
Endpoint
Name
Description
Timeframe
Primary 
Eosinophil 
histologic response 
Changes in mean number of peak eosinophils (eos) per 
high-power field (hpf) in gastrointestinal (GI) biopsies 
from baseline to Week 16
Week 16
Key 
Secondary
Clinical response: 
eosinophilic 
gastroenteritis 
(EGE) -related 
symptoms
Changes from baseline in each of 5 domain scores of 
the Izumo Scale (APPENDIX B) from baseline
•
Heartburn Symptoms domain
•
Gastric Pain Symptoms domain
•
Stomach Heaviness Symptoms domain
•
Constipation Symptoms domain
•
Diarrhea Symptoms domain
Gastric Pain Symptoms domain, Stomach Heaviness 
Symptoms domain, and Diarrhea Symptoms domain
are Symptoms of Interest of EGE
Weeks 16 and 48
Clinical and 
histologic response 
composite
The proportion of responders defined as subjects who 
achieve both clinical and histologic response:
•
Clinical response defined as the proportion of
subjects who achieve < 4/15 in each of three
Symptoms of Interest (Gastric Pain Symptoms
domain, Stomach Heaviness Symptoms domain,
and Diarrhea Symptoms domain) scores of the 
Izumo Scale from baseline
•
Histologic response defined as a > 75% reduction
of peak gastric and/or duodenal eos count from
baseline
Weeks 16 and 48
Safety and 
tolerability
Safety and tolerability evaluated by the incidence, 
severity and relationship to CC-93538 of adverse 
events (AEs), serious adverse events (SAEs), clinical 
laboratory abnormalities, changes in vital signs, 
physical examination abnormalities and the presence of 
anti-drug antibodies, including neutralizing antibodies 
when warranted
Through Week 
48
Secondary
Eosinophil 
histologic response 
Changes in mean number of peak eos per hpf in GI 
biopsies from baseline to Week 48
Week 48 
Eosinophil 
histologic response
Percent changes in mean number of peak eos per hpf in 
GI biopsies from baseline
Weeks 16 and 48
Eosinophil 
histologic response 
(> 75% reduction)
The proportion of subjects achieving eosinophilic 
histologic response defined as a > 75% reduction of 
peak gastric and/or duodenal eos count from baseline, 
respectively
Weeks 16 and 48
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Table 2:
Study Endpoints: Induction and Maintenance Phase Endpoints 
Through Week 48
Endpoint
Name
Description
Timeframe
Secondary 
(continued)
Clinical responder 
definition
Proportion of subjects who achieve < 4/15 in each of 
three Symptoms of Interest scores using the Izumo 
Scale from baseline
Gastric Pain Symptoms domain, Stomach Heaviness 
Symptoms domain, and Diarrhea Symptoms domain
are Symptoms of Interest of EGE
Weeks 16 and 48
Clinical response:
Eosinophilic 
gastrointestinal 
disorder (EGID) 
Severity Score 
Changes in total score of EGID Severity Score 
consisting of 8 symptom/laboratory scores and 2 
medical history related questions using EGID Severity 
Score (APPENDIX C for subjects ≥ 20 years at the 
time of signing the informed consent form [ICF]) or 
consisting of 8 symptom/laboratory scores and 3 
general condition related questions (APPENDIX D for
subjects from 12 to 19 years at the time of signing the
ICF/assent) from baseline
Weeks 16 and 48
Time to event
The time to event of EGE flare
Through Week 
48
Time to event
The time to event of use of rescue therapy 
Through Week 
48
Time to event
(subjects who use 
concomitant 
treatment only)
The time until concomitant corticosteroid use to zero 
(and continued by Week 48)
From Week 16 
through Week 48
Proportion of 
subjects with event
(subjects who use 
concomitant
treatment only)
The proportion of subjects for whom the dose of 
concomitant steroids is reduced to zero
Weeks 24, 32, 
40, and 48
Pharmaco-kinetics 
(PK)
Trough concentrations of CC-93538 through Week 48
Through Week 
48
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Table 2:
Study Endpoints: Induction and Maintenance Phase Endpoints 
Through Week 48
Endpoint
Name
Description
Timeframe
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Table 2:
Study Endpoints: Induction and Maintenance Phase Endpoints 
Through Week 48
Endpoint
Name
Description
Timeframe
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Table 3:
Study Endpoints: Open-label Long-term Extension Period 
Endpoints After Week 48
Endpoint
Name
Description
Timeframe
Secondary 
Safety and 
tolerability 
Safety and tolerability evaluated by the incidence, 
severity and relationship to CC-93538 of adverse 
events (AEs), serious adverse events (SAEs), 
clinical laboratory abnormalities, changes in vital 
signs, physical examination abnormalities and the 
presence of anti-drug antibodies, including 
neutralizing antibodies when warranted
Through the 
Safety Follow-up 
Visit
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Table 3:
Study Endpoints: Open-label Long-term Extension Period 
Endpoints After Week 48
Endpoint
Name
Description
Timeframe
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Table 3:
Study Endpoints: Open-label Long-term Extension Period 
Endpoints After Week 48
Endpoint
Name
Description
Timeframe
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Table 3:
Study Endpoints: Open-label Long-term Extension Period 
Endpoints After Week 48
Endpoint
Name
Description
Timeframe
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3
OVERALL STUDY DESIGN
3.1
Study Design
Study CC-93538-EG-001 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled 
induction and maintenance study to assess the efficacy and safety of CC-93538 in adult and 
adolescent subjects with EGE. The study will include a 16-week Induction Phase followed by a 
32-week Maintenance Phase and an Open-label Long-term Extension (OLE) Phase for a minimum 
of 2 years, but may extend for a longer duration. Subjects will be randomized at the beginning of 
the study into 2 treatment arms in a 2:1 ratio for the 16 weeks of the Induction Phase: CC-93538 
360 mg SC once weekly or matching placebo. Subjects who are randomized to receive CC-93538 
360 mg SC once weekly in the Induction Phase will be re-randomized in a 1:1 ratio for the 32 
weeks of the Maintenance Phase: CC-93538 360 mg SC once weekly or CC-93538 360 mg SC 
once every other week. Subjects who are randomized to receive matching placebo in the Induction 
Phase will continue to receive placebo in the Maintenance Phase.
Subjects who complete Week 16 of the Induction Phase or Week 48 of the Maintenance Phase are 
eligible to enter the OLE Phase. During the Maintenance Phase, subjects experiencing a severe 
EGE flare and/or experience worsening of EGE symptoms may also enter the OLE Phase. All 
subjects will receive CC-93538 360 mg SC once weekly in the OLE Phase. The OLE Phase is 
planned to continue for 2 years or until the marketing launch, or the subject decides to withdraw 
from the study, the investigator decides to withdraw the subject from the study, or the Sponsor 
decides to terminate the study.
An overview of the overall study design is presented in Figure 1.
Figure 1:
Overall Study Schema
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The safety monitoring of this study will be performed by an external, independent Data Monitoring 
Committee (DMC) (Section 9.9.4) in addition to routine internal review by the Safety Management 
Team (SMT) (Section 9.9.3).
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.
3.1.1
Screening Period
Prospective subjects will be assessed during a Screening Period of up to 4 weeks to confirm initial 
eligibility for the study via medical history, physical examination, review of prior therapy, clinical 
laboratory tests, and esophagogastroduodenoscopy (EGD), for evaluation of histologic and 
endoscopic findings. For the EGD and informed consent only, an extension of the screening 
window of up to 8 weeks total may be allowed to accommodate the scheduling of this procedure 
after informed consent has been obtained. The screening EGD must be performed within 8 weeks 
(56 days) of the planned Day 1 Visit for subjects to be eligible to participate in the study. All 
screening procedures should be performed during the 4-week Screening Period prior to Day 1. 
Symptoms of EGE will be assessed by the patient-reported outcome (PRO) questionnaire (referred 
to as Izumo Scale [weekly],
 
 
. Izumo scale will be completed at least the 
2 consecutive weeks before the IP administration on Day 1, but may be performed for consecutive
weeks during the screening period.
 
 Refer to Section 
6.1 for further details.
3.1.2
Induction Phase
Following a 4-week Screening Period, subjects meeting all inclusion criteria and none of the 
exclusion criteria will be eligible for enrollment in the Induction Phase. Approximately 45 subjects 
12 to 75 years of age, inclusive, with a diagnosis of EGE and with symptoms of EGE will be 
randomized 2:1 to receive CC-93538 360 mg SC once weekly (N = approximately 30) or matching 
placebo (N = approximately 15), in a double-blind fashion for 16 weeks. Subjects will be required 
to have weekly symptom scores of ≥4/15 for any of Gastric Pain Symptoms domain, Stomach 
Heaviness Symptoms domain and /or Diarrhea Symptoms domain, as assessed by the Izumo Scale
with electronic device over the 2 consecutive weeks before baseline (assessed on Day 1), and 
histologic evidence of EGE with ≥30 eos/hpf in at least 5 hpf in the stomach and/or ≥30 eos/hpf 
in at least 3 hpf in the duodenum. Both assessments will be conducted while on stable background 
therapy. Peak gastric/duodenum eos count will be confirmed by the central reader. 
Subjects weighing ≥ 30 kg will be enrolled in this study. Currently, there is no administration 
experience of CC-93538 360 mg once weekly in subjects weighing < 40 kg. Careful and close 
safety monitoring (eg, for hypersensitivity reaction) should be considered for this population. For
subjects weighing ≥ 30 kg and <40 kg, the first 3 weekly SC doses will be administered in the 
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clinic, with confirmation of concomitant medications and AEs, and those subjects will remain in 
the clinic for at least 1 hour following dosing for observation, and be monitored every 2 weeks by 
the site staff by telephone (but not limited to telephone) between regularly scheduled visits until 
Week 16 (ie, Week 6 [Day 43 ± 3 days], Week 10 [Day 71 ± 3 days], and Week 14 [Day 99 ± 3
days]).
Treatment assignment at baseline will be stratified by (with/without) concomitant use of 
corticosteroid treatment at baseline (up to 10 mg/day as the equivalent of prednisone) to ensure an 
equal balance in the treatment arms. Baseline assessments and procedures will be completed prior 
to randomization and administration of IP on Day 1. The dosage regimen of permitted anti-
inflammatory therapy (including concomitant corticosteroid treatment at baseline; up to 10 mg/day 
as the equivalent of prednisone) must be kept stable until Week 16. Subjects with a worsening of 
EGE symptoms (described in Section 6.4.2.10) during the Induction Phase will be required to 
complete the EGE Flare Assessment Visit per the Table of Events (Table 4). The subject may 
continue to participate with concomitant rescue therapy as needed and will be eligible to enter the 
OLE Phase following completion of Week 16 of the Induction Phase, or discontinue from the study. 
Details are described in Section 3.1.6. All attempts should be made to complete the Induction 
Phase.
Clinical laboratory tests, vital signs, physical examinations 
 
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 assess immunogenicity), concomitant medications, and AE/SAE assessments will
be performed according to the Table of Events presented in Table 4. 
3.1.3
Maintenance Phase
After completion of Week 16 of the Induction Phase, eligible subjects will continue participation 
and enter the Maintenance Phase if none of the conditions disqualifying subjects from eligibility 
have been met as described in Section 3.1.6. A placebo-controlled Maintenance Phase will allow 
for a determination of persistence of treatment effect and the overall long-term efficacy of CC-
93538.
The Maintenance Phase treatment arms include CC-93538 360 mg SC once every week, CC-93538 
360 mg SC once every other week, and matching placebo. Subjects who are randomized to receive 
CC-93538 360 mg SC once weekly in the Induction Phase will be re-randomized (1:1) to CC-
93538 360 mg SC once weekly or CC-93538 360 mg SC once every other week at the beginning
of the Maintenance Phase, and subjects who are randomized to receive matching placebo in the
Induction Phase will continue placebo in the Maintenance Phase. A double-blind fashion will be
kept in the Maintenance Phase.
If the reduction of EGE-related symptoms is observed at/after Week 16 (in the Maintenance 
Phase), the investigator should begin tapering the dosage regimen of concomitant corticosteroid 
treatment after Week 16. The dose reduction should be 2.5 mg/week (as the equivalent of 
prednisone). If the symptoms worsen after tapering of the dosage regimen of concomitant 
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corticosteroid treatment, the dose can be increased until it is the same as the baseline dose at the 
Induction Phase.
Subjects who complete Week 48 of the Maintenance Phase have 2 options: 
1. to enter the Open-label Long-term Extension Phase (Section 3.1.4)
2. to return for an Interim and a Final Safety Follow-up Visit at 8 and 16 weeks, respectively,
after the last dose of IP (at Week 55 and Week 63 for study completers) (Section 3.1.5)
Subjects with a worsening of EGE symptoms (described in Section 6.4.2.10) during the 
Maintenance Phase will be required to complete the EGE Flare Assessment Visit per the Table of 
Events (Table 5). The subjects will need to discontinue participation in the Maintenance Phase and 
may be eligible to enter the OLE Phase. Details are described in Section 3.1.6.
Clinical laboratory tests, vital signs, physical examinations 
 
pregnancy tests (FCBP subjects only), EGD, clinical symptom assessment, subject-reported 
outcomes, serum CC-93538 PK concentrations, serum antibodies to CC-93538 (to assess 
immunogenicity), concomitant medications, and AE/SAE assessments will be performed 
according to the Table of Events presented in Table 5.
 
The study blind should be maintained for persons responsible for the ongoing conduct of the study 
(after all subjects have completed the Week 48 assessments for endpoint analysis). Blinded persons 
may include but are not limited to: the Clinical Research Physician (also referred to as Clinical 
Trial Physician), Clinical Research Scientist, Clinical Trial Manager, Study Statistician, Data 
Manager, Programmers, and Clinical Research Associates.
3.1.4
Open-label Long-term Extension Phase 
Subjects who meet one of the following criteria with respect to participation in the Induction Phase 
and the Maintenance Phase will be given the opportunity to participate in the OLE Phase.
•
Subjects who do not qualify for entry into the Maintenance Phase including:
−
Subjects who experience a severe EGE flare requiring concomitant rescue therapy during
the Induction Phase will be eligible for the OLE Phase after completion of Week 16 of the
Induction Phase
•
Subjects who cannot complete the Maintenance Phase including
−
Subjects who experience a severe EGE flare requiring concomitant rescue therapy and/or
worsening of EGE symptoms (for 2 consecutive visits [4 weeks apart] at the beginning of
or during the Maintenance Phase will be eligible to enter the OLE Phase at the Early
Termination (ET) Visit
•
Subjects who complete Week 48 of the Maintenance Phase will be eligible for the OLE Phase
after completion of Week 48 of the Maintenance Phase.
The OLE Phase baseline assessments will be obtained from either the Induction Phase Week 16
Visit assessments, the Maintenance Phase Week 48 Visit assessments, or the Maintenance Phase 
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EGE Flare Assessment Visit, and ET Visit assessments, as applicable. Additional OLE baseline 
assessments not performed at the final Induction Phase Visit (Week 16), final Maintenance Phase 
Visit (Week 48) or the Maintenance Phase EGE Flare Assessment Visit and ET Visit assessments
should be conducted at the OLE Day 1 Visit in accordance with the Table of Events (Table 6); it 
is anticipated that this should occur for most subjects on the same day. Subjects will not be allowed
to enroll in the OLE Phase and receive IP on OLE Day 1 if there will be a delay of > 21 days from 
dosing in the final Induction Visit or the final dosing in the Maintenance Phase unless discussed 
with the Medical Monitor (refer to Section 6.3.2). The 2 Safety Follow-up Visits are not required 
for subjects enrolling in the OLE Phase, after the final Induction Phase Visit, final Maintenance 
Phase Visit or the Maintenance Phase EGE Flare Assessment Visit and ET Visit assessments.
During the OLE Phase, all subjects will be administered CC-93538 at a dose of 360 mg SC once 
weekly as long as they are participating in the study, until the investigator decides to withdraw the 
subject, or the Sponsor decides to terminate/complete the study. Individual subject participation in 
the OLE Phase may be for a minimum of 2 years but may extend for a longer duration. The dosing 
regimen in the OLE Phase may be revised through an amendment to the study protocol once results 
from the Maintenance Phase are available and the most effective and safest dosing regimen is 
confirmed.
Depending on the EGE symptoms of subject, the investigator may decrease/increase the dose of 
concomitant corticosteroid treatment after OLE Visit 1 during the OLE Phase.
Subjects with a worsening of EGE symptoms (described in Section 6.4.2.10) during the OLE Phase 
will be required to complete the EGE Flare Assessment Visit per the Table of Events (Table 6).
Clinical laboratory tests, vital signs, physical examinations 
 
pregnancy tests (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, 
 
 will be performed in accordance with the Table 
of Events (Table 6). 
Subjects may discontinue from the OLE Phase at any time. Subjects who discontinue the study at 
or after 2 years of participation (the fourth quarter Visit in Year 2 [Week 104]) will complete an 
OLE-End of Treatment (EoT) Visit within 2 weeks after receiving the final dose of CC-93538,
and an 8-week Interim and a 16-week Final Safety Follow-up Visit at 8 weeks 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 OLE-ET Visit (Table 6).
3.1.5
Early Termination, End of Treatment and Safety Follow-up Visits
Subjects who complete Week 48 of the Maintenance Phase and do not participate in the OLE Phase 
will be required to return for an Interim and a Final Safety Follow-up Visit at 8 and 16 weeks, 
respectively, after the last dose of IP (at Week 55 and Week 63 for study completers). Subjects 
may discontinue from the study at any time. Subjects who discontinue the study during the 
Maintenance Phase will complete ET Visit and subjects who discontinue the study during the OLE 
Phase (and before OLE Week 104) will complete an OLE-ET Visit within 2 weeks after their final 
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dose of IP. In addition to the ET or the OLE-ET Visit procedures, subjects exiting the study early 
will also return for the Interim and the Final Safety Follow-up Visits (Section 6.3.1). However, 
subjects who are permanently discontinued from IP and continue study participation in order to 
complete safety and efficacy assessments will return for the Interim and Final Safety Follow-up 
Visits after their last study visit (refer to Section 6.3.1).
For subjects who discontinue the study at or after 2 years of participation (the fourth quarter visit 
in OLE Phase Year 2 [OLE Week 104]) will complete an OLE-EoT Visit (Section 6.2.2) within 2 
weeks after their final dose of IP and an 8-week Interim and a 16-week Final Safety Follow-up 
Visit.
3.1.6
Worsening of EGE Symptoms and EGE flare
Subjects with a worsening of EGE symptoms (described in Section 6.4.2.10) during the study, 
either in the Induction Phase, Maintenance Phase, or the OLE Phase will be required to complete 
the EGE Flare Assessment Visit per the Table of Events (Table 4, Table 5, and Table 6). For 
subjects with a worsening of EGE symptoms and/or EGE flare, an EGD may be required to 
determine if rescue therapy is clinically indicated. The results of the gastric/duodenal eos count 
will be blinded to investigative sites with the possible exception of screening during the Induction 
Phase (see below). After randomization, a local histologic assessment of EGD biopsy samples 
should not be performed, unless required for safety reasons (eg, severe EGE flare, etc).
Any worsening of EGE symptoms during study participation will be documented as an EGE flare. 
See Section 6.4.2.10 and Section 6.2.1 for the protocol definition of EGE flare and EGE Flare 
Assessment Visit details, respectively. 
Subjects with increased signs and symptoms of EGE are instructed to contact the investigator
and/or study staff to determine if an EGE Flare Assessment Visit is warranted.
Induction Phase
Subjects experiencing a severe EGE flare and/or worsening of EGE symptoms (for 2 consecutive 
visits [4 weeks apart], described in Section 6.4.2.10) in the Induction Phase may continue to 
participate with concomitant rescue therapy as needed and will be eligible to enter the OLE Phase 
following completion of Week 16 of the Induction Phase. Subjects with a severe EGE flare in the 
Induction Phase will not qualify for entry into the Maintenance Phase.
If the gastric/duodenal eos count is required to determine the need for emergent rescue therapy 
during the Induction Phase, the results of the gastric/duodenal eos count will be disclosed as long 
as the investigator requires the result. The subject is to be discontinued from the study and will not 
be allowed to enter either the Maintenance Phase or the OLE Phase. All attempts should be made 
to complete the Induction Phase.
Subjects experiencing a mild to moderate EGE flare in the Induction Phase will continue to the 
Maintenance Phase of the study.
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Maintenance Phase
Subjects who experience a severe EGE flare and/or worsening of EGE symptoms (for 2 
consecutive visits [4 weeks apart], described in Section 6.4.2.10) at the beginning of or during the 
Maintenance Phase will need to discontinue participation in the Maintenance Phase and may be 
eligible to enter the OLE Phase at the ET Visit.
If the gastric/duodenal eos count is required to determine the need for emergent rescue therapy 
during the Maintenance Phase, the results of the gastric/duodenal eos count will be disclosed as 
long as the investigator requires the result. The subject may also be eligible to enter the OLE Phase.
Subjects experiencing a mild to moderate EGE flare in the Maintenance Phase will continue the 
study and will be eligible to enter the OLE Phase following the completion of the Week 48 Visit.
OLE Phase
During the OLE Phase, subjects who demonstrate a persistent lack of improvement, worsening of 
EGE symptoms or severe EGE flare should be evaluated if continuation of study treatment is 
appropriate. While subjects will have the opportunity to continue participation in the OLE Phase 
with use of rescue therapy as needed, based on clinical judgment, the investigator should 
discontinue any subject if study participation no longer is in the best interest of the subject.
Subjects who are discontinued from the OLE Phase will be asked to complete an OLE-ET/EoT
Visit (Section 6.2.2) and the two Safety Follow-up Visits (Section 6.3.1).
3.2
Study Duration for Subjects 
The maximum duration of subject participation in the Screening Period, Induction Phase and 
Maintenance Phase is approximately 72 weeks, including the Interim and the Final Safety Follow-
up Visits. Subjects will participate for up to 4 weeks in the Screening Period (the screening EGD 
may be completed up to 8 weeks prior to Day 1), 16 weeks in the Induction Phase, and 32 weeks 
in the Maintenance Phase of the study. Subjects completing the Maintenance Phase who do not 
continue IP administration in the OLE Phase will complete the Interim and the Final Safety 
Follow-up Visits (at 8 and 16 weeks) after final IP administration.
Subjects who enter the OLE Phase will complete the OLE baseline assessments on Day 1,
excluding those obtained from either the Induction Phase Week 16 Visit, the Maintenance Phase 
Week 48 Visit, or the ET Visit during the Maintenance Phase, as applicable. Subjects will receive 
weekly doses of IP during the OLE Phase for a minimum duration of 2 years and will complete an 
OLE-ET Visit or an OLE-EoT Visit within 2 weeks after the final dose and an Interim and a Final 
Safety Follow-up Visits at 8 and 16 weeks, respectively, after the final dose. Individual subject 
participation in the OLE Phase may be a minimum of 2 years but may extend for a longer duration, 
provided the subject does not withdraw from the OLE Phase prior to Year 2 of the OLE.
Subjects may continue participation to the OLE Phase as long as they tolerate treatment and are 
receiving benefit from participation in the study. Participation may continue until the marketing 
launch (the terms “this study” in this protocol will automatically be replaced with “post-marketing 
clinical study” on and after the date of marketing approval in Japan), or the subject decides to 
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Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
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withdraw from the study, the investigator decides to withdraw the subject from the study, or the 
Sponsor decides to terminate the study (see Section 12.8).
3.3
End of Trial
The End of Trial is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up (the Final Safety Follow-up Visit), or the date of receipt of the last data 
point from the last subject that is required for primary, secondary 
 analysis, as 
prespecified in the protocol, whichever is the later date.
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4
STUDY POPULATION
4.1
Number of Subjects 
The study population will consist of males and females aged 12 to 75 years (inclusive) with EGE. 
Forty-five adults (aged 18 to 75 years) and adolescents (aged 12 to 17 years) will be enrolled in 
the study.
4.2
Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subject must be ≥ 12 years and ≤ 75 years of age and have a body weight of ≥ 30 kg at the 
time of signing the informed consent form (ICF). 
If a subject is < 18 years old, subject assent must be obtained and parental/legal 
representative consent is required.
2. Subjects who were diagnosed with EGE at least 3 months prior to study entry
3. Subject has histologic evidence of EGE defined as ≥ 30 eos/hpf in at least 5 hpf in the stomach 
and/or ≥ 30 eos/hpf in at least 3 hpf in the duodenum while on stable background therapy (eg, 
corticosteroids, however a stable dose of prednisone [up to 10 mg/day] is allowed, see 
Exclusion Criterion 9) for EGE. The histologic criterion for diagnosis of EGE must be 
confirmed by a centrally read histological assessment of an EGD specimen during the 
Screening Period prior to randomization. 
4. Subject has weekly symptom scores of ≥ 4/15 for any of Gastric Pain Symptoms domain, 
Stomach Heaviness Symptom domains, and /or Diarrhea Symptoms domain as assessed by the 
Izumo Scale with electronic device for the 2 consecutive weeks before the IP administration 
on Day 1.
5. Subjects must agree to maintain a stable diet (including any food elimination diet for the 
treatment of food allergy or EGE) from the first Screening Visit and throughout the duration 
of the study, and subjects must have maintained a stable diet for at least 4 weeks prior to the 
first Screening Visit. Subjects must agree not to introduce any changes in their diet while 
participating in the study. If the subject is currently successfully treated for EGE with dietary 
modifications (eg, food elimination diet) and resulting in a complete response to EGE, the 
subject is not allowed to participate to this study. 
6. Subjects currently receiving systemic corticosteroids, inhaled corticosteroids, proton pump 
inhibitors (PPIs), leukotriene receptor antagonists (eg, montelukast), or mast cell stabilizers 
(eg, cromolyn sodium) for indications of EGE or other than EGE, or medium potency topical 
corticosteroids (eg, mometasone furoate cream or lotion) for dermatologic conditions, must 
maintain stable doses/regimens for at least 4 weeks prior to the first Screening Visit and 
regimens must remain stable throughout the duration of the study except for systemic 
corticosteroids (the dose/regimen of systemic corticosteroids must remain stable for the 16 
weeks of the Induction Phase). If recently discontinued, the medication must have been 
discontinued at least 4 weeks prior to the first Screening Visit.
7. Female subjects of childbearing potential must agree to practice a highly effective method of 
contraception. Highly effective methods of contraception are those that alone or in combination 
result in a failure rate of a Pearl index of less than 1% per year when used consistently and 
correctly.
An FCBP is a female who: 1) has achieved menarche at some point; and 2) has not undergone 
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a hysterectomy, 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 follow the criteria below:
a.
Have 2 negative pregnancy tests as verified by the investigator prior to starting study
therapy. She must agree to ongoing pregnancy testing during the course of the study and
through the Final 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 (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]):
−
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.
−
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.
−
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
8. Subject is willing to receive weekly SC injections throughout the study.
9. Subject must understand and voluntarily sign an ICF prior to any study-related
assessments/procedures being conducted.
10. Subject is willing and able to adhere to the study visit schedule and other protocol
requirements.
∗True abstinence is acceptable when this is the preferred and usual lifestyle of the subject. Periodic abstinence (eg,
calendar, ovulation, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), and lactational
amenorrhea method are not acceptable methods of contraception.
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4.3
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
1. Subject who has ascites requiring treatment or symptomatic ascites
2. Subject who has a history of inflammatory bowel disease (including Crohn’s disease and
ulcerous colitis), achalasia or esophageal surgery.
3. Subject who has a history of GI bleeding disorders and/or demonstrates presence of
esophageal varices.
4. Subject who has other causes of gastric and/or duodenal eosinophilia or eosinophilic
granulomatosis with polyangiitis (EGPA).
5. 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 [HES], Mendelian disorder associated with EGE, or
cardiovascular condition, or neurologic or psychiatric illness that compromises the
prospective subject's ability to accurately document symptoms of EGE).
•
Diagnosis of HES is based on standard criteria (blood eosinophils >1500/μL with
involvement of either the heart, nervous system, and/or bone marrow).
6. 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, upper or lower GI bleed, inflammatory bowel disease, 
, etc).
7. Subject has a diagnosis of celiac disease or active Helicobacter pylori infection as
determined by screening EGD or a history of celiac disease diagnosed by prior EGD.
8. Subject
demonstrates evidence of immunosuppression or is receiving systemic
immunosuppressive or immunomodulating drugs with the exception of corticosteroids
allowed as background or rescue therapy (eg, 
 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 the first Screening Visit. Any use of these medications
will be prohibited during the study.
9. Subject who uses systemic corticosteroids exceeding the equivalent of up to 10 mg/day of
prednisone within 4 weeks prior to the first Screening Visit.
10. Subject is currently receiving a high potency topical corticosteroid (eg, augmented
betamethasone dipropionate, clobetasol propionate, etc) for dermatologic use. Prospective
subjects must not have received a high potency topical corticosteroid for dermatologic use
within 8 weeks of the first Screening Visit. Any use will be prohibited during the study.
11. Subject has received oral or sublingual immunotherapy within 6 months of the first
Screening Visit; any use will be prohibited during the study. Subjects receiving SC
immunotherapy may participate but must be on stable doses for at least 3 months prior to
the first Screening Visit and during the study.
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12. Subject is receiving concurrent treatment with another IP, including through participation
in an interventional trial for COVID-19. Prospective subjects may not participate in a
concurrent IP study or have received an IP within 5 drug half-lives prior to signing the
ICF/assent for this study. Further, for subjects who received an investigational COVID-19
vaccine as part of a clinical trial prior to the first Screening Visit, enrollment must be
delayed until the impact of the vaccine is stabilized, as determined by discussion between
the investigator and the Clinical Trial Physician.
13. Subject has received a live (including attenuated) vaccine within 1 month prior to the first
Screening Visit or anticipates the need to be vaccinated with a live (including 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.
14. Subject has previously received CC-93538 treatment (formerly known as RPC4046 and
ABT-308) through participation in any other CC-93538 clinical study.
15. Subject has liver function impairment or persisting elevations of aspartate
aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) or alanine
aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) that are 2 times the
upper limit of normal (ULN), or total bilirubin 1.5 times the ULN. Subjects with elevations
in total bilirubin that are due to Gilbert Syndrome and that are not clinically meaningful
may participate.
16. 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 to randomization.
17. Subject has an ongoing infection (eg, hepatitis B or C, human immunodeficiency virus
[HIV], or tuberculosis as defined by standard medical guidelines and as outlined in Section
6.1).
18. Severe infection within 4 weeks prior to screening
•
Additionally, in the case of prior SARS-CoV-2 infection, symptoms must have
completely resolved, and based on investigator assessment in consultation with the
Clinical Trial Physician, there are no sequelae that would place the participant at a
higher risk of receiving investigational treatment
19. Subject has known hereditary fructose intolerance (HFI).
20. Subject is pregnant or lactating.
21. Subject has a history of idiopathic anaphylaxis or a major immunologic reaction (such as
anaphylactic reaction, anaphylactoid reaction, or serum sickness) to an Immunoglobulin
G (IgG) containing agent.
Note: a subject who has a known hypersensitivity to any ingredient in the IP is also
excluded.
22. Subject has a history of cancer or lymphoproliferative disease, other than a successfully
treated non-metastatic cutaneous squamous cell or basal cell carcinoma or adequately
treated cervical carcinoma in situ, within 5 years of screening.
23. Subject has a history of alcohol or drug abuse diagnosed within 5 years prior to initiation
of screening.
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0
Final: 20 Sep 2023
64
24. Subject has any significant medical condition, laboratory abnormality, or psychiatric
illness that would prevent the subject from participating in the study.
25. 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.
26. Subject has any condition that confounds the ability to interpret data from the study.
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
65
5
TABLES OF EVENTS
Table 4:
Table of Events for the Induction Phase
Study
Procedures
Screen-
inga
Induction Phase Treatment Period
EGE Flare 
Assessment 
Visit e
ET 
Visit f
Interim 8-
week
Safety 
Follow-up 
Visit g
Final 16-
week 
Safety 
Follow-
up Visit g
Visit Label
Visit 1b
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8 c, d
Visit Week
(Window)
Day
-28 to -
1
Day 1
Week 1
(Day 
8±3d)
Week 2
(Day 
15±3d)
Week 3
(Day 
22±3d)
h
Week 4
(Day 
29±3d)
h
Week 8
(Day 
57±3d)
h
Week 12
(Day 
85±3d) h
Week 16
(Day 
113±3d) h
Week 23
(Day 
162±7d)
Week 31
(Day 
218±7d)
Informed 
consent/assent
X
-
-
-
-
-
-
-
-
-
-
-
-
Inclusion/
exclusion criteria
X
X
-
-
-
-
-
-
-
-
-
-
-
Demographics/base-
line characteristics
X
-
-
-
-
-
-
-
-
-
-
-
-
Medical history
X
-
-
-
-
-
-
-
-
-
-
-
-
Prior therapy
X
-
-
-
-
-
-
-
-
-
-
-
-
Concomitant 
therapy
X
X
(X)h
X
(X)h
X
X
X
X
X
X
X
X
AEs/SAEs
X
X
(X)h
X
(X)h
X
X h
X h
X h
X
X
X
X
Hematology and 
chemistry (pre-
dose) i, j
X
X
-
-
-
X
X
X
X
X
X
X
X
Coagulation panel
X
-
-
-
-
-
-
-
-
-
-
-
-
Urinalysis (pre-
dose) i
X
X
-
-
-
X
-
-
X
X
X
X
X
Testing for hepatitis 
B and C and HIV
X
-
-
-
-
-
-
-
-
-
-
-
-
TB assessment
X
-
-
-
-
-
-
-
-
-
-
-
-
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
66
Table 4:
Table of Events for the Induction Phase
Study
Procedures
Screen-
inga
Induction Phase Treatment Period
EGE Flare 
Assessment 
Visit e
ET 
Visit f
Interim 8-
week
Safety 
Follow-up 
Visit g
Final 16-
week 
Safety 
Follow-
up Visit g
Visit Label
Visit 1b
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8 c, d
Visit Week
(Window)
Day
-28 to -
1
Day 1
Week 1
(Day 
8±3d)
Week 2
(Day 
15±3d)
Week 3
(Day 
22±3d)
h
Week 4
(Day 
29±3d)
h
Week 8
(Day 
57±3d)
h
Week 12
(Day 
85±3d) h
Week 16
(Day 
113±3d) h
Week 23
(Day 
162±7d)
Week 31
(Day 
218±7d)
Pregnancy test 
(FCBP only) k
X
X
-
-
-
X
X
X
X
-
X
X
X
Physical 
examination l
X
X
-
-
-
X
X
X
X
-
X
X
X
Height (cm)
X
-
-
-
-
-
(X)m
-
(X)m
(X) m
(X)m
(X)m
(X)m
Weight (kg)
X
X
-
X
-
X
X
X
X
X
X
X
X
Vital signs
X
X
-
X
-
X
X
X
X
X
X
X
X
Electrocardiogram 
(ECG)
X
-
-
-
-
-
-
-
-
-
-
-
-
Serum antibodies to 
CC-93538 i
-
X
-
-
-
X
X
-
X
-
X
X
X
Serum CC-93538 
PK assessment i
-
X
-
X
-
X
X
X
X
-
X
X
X
Izumo Scale q
X
X
X
X
X
X
X
X
X
-
X
X
X
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
67
Table 4:
Table of Events for the Induction Phase
Study
Procedures
Screen-
inga
Induction Phase Treatment Period
EGE Flare 
Assessment 
Visit e
ET 
Visit f
Interim 8-
week
Safety 
Follow-up 
Visit g
Final 16-
week 
Safety 
Follow-
up Visit g
Visit Label
Visit 1b
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8 c, d
Visit Week
(Window)
Day
-28 to -
1
Day 1
Week 1
(Day 
8±3d)
Week 2
(Day 
15±3d)
Week 3
(Day 
22±3d)
h
Week 4
(Day 
29±3d)
h
Week 8
(Day 
57±3d)
h
Week 12
(Day 
85±3d) h
Week 16
(Day 
113±3d) h
Week 23
(Day 
162±7d)
Week 31
(Day 
218±7d)
EGID Severity 
Score r
-
X
-
-
-
-
X
-
X
X
X
X
X
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
68
Table 4:
Table of Events for the Induction Phase
Study
Procedures
Screen-
inga
Induction Phase Treatment Period
EGE Flare 
Assessment 
Visit e
ET 
Visit f
Interim 8-
week
Safety 
Follow-up 
Visit g
Final 16-
week 
Safety 
Follow-
up Visit g
Visit Label
Visit 1b
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8 c, d
Visit Week
(Window)
Day
-28 to -
1
Day 1
Week 1
(Day 
8±3d)
Week 2
(Day 
15±3d)
Week 3
(Day 
22±3d)
h
Week 4
(Day 
29±3d)
h
Week 8
(Day 
57±3d)
h
Week 12
(Day 
85±3d) h
Week 16
(Day 
113±3d) h
Week 23
(Day 
162±7d)
Week 31
(Day 
218±7d)
EGD with tissue 
biopsies v
X
-
-
-
-
-
-
-
X
X w
X x
-
-
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
69
Table 4:
Table of Events for the Induction Phase
Study
Procedures
Screen-
inga
Induction Phase Treatment Period
EGE Flare 
Assessment 
Visit e
ET 
Visit f
Interim 8-
week
Safety 
Follow-up 
Visit g
Final 16-
week 
Safety 
Follow-
up Visit g
Visit Label
Visit 1b
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8 c, d
Visit Week
(Window)
Day
-28 to -
1
Day 1
Week 1
(Day 
8±3d)
Week 2
(Day 
15±3d)
Week 3
(Day 
22±3d)
h
Week 4
(Day 
29±3d)
h
Week 8
(Day 
57±3d)
h
Week 12
(Day 
85±3d) h
Week 16
(Day 
113±3d) h
Week 23
(Day 
162±7d)
Week 31
(Day 
218±7d)
Entry to 
Maintenance Phase 
y
-
-
-
-
-
-
-
-
X z
-
-
-
-
Randomization via 
IWRS
-
X
-
-
-
-
-
-
-
-
-
-
-
IP administration aa
-
X
Xh
Xh
Xh
X
X
X
X
-
-
-
-
Abbreviations: AE = adverse event; 
 COVID-19: = Coronavirus disease 2019; d
= day; ECG = electrocardiogram; 
EGD = esophagogastroduodenoscopy; EGE = eosinophilic gastroenteritis; EGID 
= eosinophilic gastrointestinal disorder; 
 ePRO = electronic patient-reported outcome; 
 
 ET = Early Termination; FCBP = female of childbearing potential; 
 
HIV = human immunodeficiency virus; 
 
 IP = investigational product; IWRS = Interactive Web Response System;
 PK = pharmacokinetic(s); 
PRO = patient-reported outcome; SAE = serious adverse event; 
 
 TB = tuberculosis; 
a. All assessments must be completed within 4 weeks prior to Day 1, except for EGD with tissue biopsies and informed consent, which must be completed within
8 weeks prior to Day 1.
b. The Day 1 assessments will serve as baseline measurements and will be conducted before dose administration.
c. For subjects continuing in the Maintenance Phase, Visit 8 (Week 16) of the Induction Phase will also be the first visit in the Maintenance Phase or the Open -
label Long-term Extension Phase. See Table 5 and Table 6 for the Table of Events for the Maintenance Phase or Open-label Long-term Extension Phase.
d. In the event of scheduling challenges, EGD may be performed with a + 7 days visit window. All assessments are to be performed prior to IP administration for
the first day of dosing in the Maintenance Phase.
e. An EGE Flare Assessment Visit should be scheduled as close as possible to the time that an EGE flare is suspected. Note that laboratory samples do not need to
be a pre-dose draw unless the subject is expected to dose later that day.
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
70
f. Subjects who discontinue the study prior to completing the 16-week Induction Phase will be asked to complete an ET Visit and an Interim and a Final Safety
Follow-up Visit at 8 weeks and at 16 weeks, respectively, after final IP administration for the assessment of safety and clinical status. Early Termination
procedures performed at the EGE Flare Assessment Visit do not need to be repeated for subjects discontinuing the study prematurely due to an EGE flare.
g. Subjects who complete the Induction Phase and do not enter either the Maintenance Phase or OLE Phase will be asked to complete the Interim 8-week Safety
Follow-up Visit (8 weeks after final IP administration; at Week 23 for subjects who complete the Induction Phase) and the Final 16-week Safety Follow-up
Visit (16 weeks after final IP administration; at Week 31 for subjects who complete the Induction Phase) for the assessment of safety and clinical status. For
subjects exiting the study before completing the Induction Phase, these visits should occur at 8 and 16 weeks following the last dose of IP (ie, visits may occur
before Weeks 23 and 31). However, subjects who are permanently discontinued from IP and continue study participation will return for the Interim and Final
Safety Follow-up Visits 8 and 16 weeks after their last study visit instead of their last dose of IP (eg, Week 16 or the ET Visit).
h. Collection of concomitant therapy and confirmation of AE/SAE should be performed for subjects weighing from 30 to 40 kg at Visit 2 and Visit 4. If necessary,
additional clinical laboratory tests may be performed. Also, the first 3 weekly SC doses will be administered in the clinic with confirmation of concomitant
medications and AEs, and those subjects will remain in the clinic for at least 1 hour following dosing for observation and be monitored every 2 weeks by the
site staff by telephone (but not limited to telephone) between regularly scheduled visits until Week 16 (ie, Week 6 [Day 43 ± 3 days], Week 10 [Day 71 ± 3
days], and Week 14 [Day 99 ± 3 days]).
i. Pre-dose collection, except for both Safety Follow-up Visits (if applicable), the ET Visit (if applicable), and the EGE Flare Assessment Visit (if applicable).
j. Fasting lipid panel and fasting glucose (instead of random glucose) will only be conducted at Day 1, Week 16, and the ET Visit (if applicable).
k. For females of childbearing potential (FCBP), a serum pregnancy test at screening, urine (or serum) pregnancy test at Day 1, and urine pregnancy tests at
subsequent visits are required. 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.
l. Complete physical examination will be conducted at screening, Day 1, Week 16, both Safety Follow-up Visits (if applicable), and at the ET Visit (if applicable).
Abbreviated physical examination will be conducted at Weeks 4, 8, and 12.
m.For only subjects aged from 12 to 19 years at the time of signing the ICF/assent, height will be measured at Week 8, Week 16, the EGE Flare Assessment Visit,
both Safety Follow-up Visits and ET Visit in which the EGID severity scoring is scheduled.
q. The Izumo Scale is to be completed during the Screening Period for at least the 2 consecutive weeks before the IP administration on Day 1 and weekly (at the
same time as much as possible) from Day 1 through Week 16 using a handheld device (ePRO instrument). For subjects who are required to complete the Safety
Follow-up Visits, the Izumo Scale will also be assessed for at least the prior week at each of the 2 Safety Follow-up Visits. The ePRO instrument will be
distributed to subjects at the Screening Visit. Subjects will not be able to complete a questionnaire more than 3 days before/after it is due and will not be able
to go back and make any corrections or changes to the data originally entered.
r. The height obtained at the most recent visit can be used to calculate the EGID severity score for subjects from 12 to 19 years at the time of signing the ICF/assent.
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
71
v. Esophagogastroduodenoscopy (EGD) biopsies 
. It is recommended to avoid the screening EGD
to perform during the last 2 weeks of screening just prior to Day 1.
w.EGD is required at EGE Flare Assessment Visits to determine if use of rescue therapy is clinically indicated. Alternatively, if endoscopy is conducted as part of
an emergency department visit or hospitalization for the EGE flare, data should be collected for the EGE Flare Assessment Visit EGD requirement. All attempts
should be made to collect biopsy samples, and these samples should be sent to the central reader for histologic analysis.
x. EGD is not required at Early Termination Visits that occur before Week 8 of the study.
y. The investigator will confirm the subject’s suitability for entry to the Maintenance Phase according to protocol requirements detailed in Section 6.4.2.11.
z. If a subject meets the rescue criteria detailed in Section 6.4.2.10, the subject can enter the OLE Phase.
aa. Once weekly IP administration (CC-93538 or placebo: subcutaneous [SC] doses on Day 1 followed by SC doses weekly from Week 1 through Week 15 [ie, a
total of 16 weekly SC doses inclusive of the Day 1 dose]). The first 3 weekly SC doses will be 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.
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
72
Table 5:
Table of Events for the Maintenance Phase
Study Procedures
Maintenance Phase Treatment Period
EGE 
Flare 
Asses
sment 
Visit b
ET 
Visit 
c
Interim 
8-week
Safety
Follow-
up 
Visit d
Final 
16-week
Safety
Follow-
up 
Visit d
Visit Label
Visit 
8 a
Visit 
9
Visit 
10
Visit 
11
Visit 
12
Visit 
13
Visit 
14
Visit 
15
Visit 
16
Visit Week 
(Window)
Week 
16
(Day 
113±3d)
Week 
20
(Day 
141±3d)
Week 
24
(Day 
169±3d)
Week 
28
(Day 
197±3d)
Week 
32
(Day 
225±3d)
Week 
36
(Day 
253±3d)
Week 
40
(Day 
281±3d)
Week 
44
(Day 
309±3d)
Week 
48
(Day 
337±3d)
Week 55
(Day 
386±7d)
Week 63
(Day 
442±7d)
Confirm eligibility
X
-
-
-
-
-
-
-
-
-
-
-
-
Concomitant therapy
X
X
X
X
X
X
X
X
X
X
X
X
X
AEs/SAEs
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematology e
X
X
X
X
X
X
X
X
X
X
X
X
X
Chemistry e, f
X
-
X
-
X
-
X
-
X
X
X
X
X
Urinalysis e
X
-
-
-
-
-
-
-
X
X
X
X
X
Urine pregnancy test 
(FCBP only) g
X
X
X
X
X
X
X
X
X
-
X
X
X
Physical examination 
h
X
-
-
-
X
-
-
-
X
-
X
X
X
Height (cm)
(X)i
-
-
-
(X) i
-
-
-
(X)i
(X)i
(X) i
(X)i
(X)i
Weight (kg)
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
Serum antibodies to 
CC-93538 e
X
X
X
X
X
-
-
-
X
-
X
X
X
Serum CC-93538 PK 
assessment e
X
X
X
X
X
X
X
-
X
-
X
X
X
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
73
Table 5:
Table of Events for the Maintenance Phase
Study Procedures
Maintenance Phase Treatment Period
EGE 
Flare 
Asses
sment 
Visit b
ET 
Visit 
c
Interim 
8-week
Safety
Follow-
up 
Visit d
Final 
16-week
Safety
Follow-
up 
Visit d
Visit Label
Visit 
8 a
Visit 
9
Visit 
10
Visit 
11
Visit 
12
Visit 
13
Visit 
14
Visit 
15
Visit 
16
Visit Week 
(Window)
Week 
16
(Day 
113±3d)
Week 
20
(Day 
141±3d)
Week 
24
(Day 
169±3d)
Week 
28
(Day 
197±3d)
Week 
32
(Day 
225±3d)
Week 
36
(Day 
253±3d)
Week 
40
(Day 
281±3d)
Week 
44
(Day 
309±3d)
Week 
48
(Day 
337±3d)
Week 55
(Day 
386±7d)
Week 63
(Day 
442±7d)
Izumo Scale l
X
X
X
X
X
X
X
X
X
-
X
X
X
EGID Severity Score
m
X
-
-
-
X
-
-
-
X
X
X
X
X
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
74
Table 5:
Table of Events for the Maintenance Phase
Study Procedures
Maintenance Phase Treatment Period
EGE 
Flare 
Asses
sment 
Visit b
ET 
Visit 
c
Interim 
8-week 
Safety 
Follow-
up 
Visit d
Final 
16-week 
Safety 
Follow-
up 
Visit d
Visit Label
Visit 
8 a
Visit 
9
Visit 
10
Visit 
11
Visit 
12
Visit 
13
Visit 
14
Visit 
15
Visit 
16
Visit Week 
(Window)
Week 
16
(Day 
113±3d)
Week 
20
(Day 
141±3d)
Week 
24
(Day 
169±3d)
Week 
28
(Day 
197±3d)
Week 
32
(Day 
225±3d)
Week 
36
(Day 
253±3d)
Week 
40
(Day 
281±3d)
Week 
44
(Day 
309±3d)
Week 
48
(Day 
337±3d)
Week 55
(Day 
386±7d)
Week 63
(Day 
442±7d)
EGD with tissue 
biopsies p
X
-
-
-
-
-
-
-
X
X q
X r
-
-
Entry to OLE Phase
-
-
-
-
-
-
-
-
X s
-
(X) s
-
-
Re randomization via 
IWRS 
X t
-
-
-
-
-
-
-
-
-
-
-
-
IP administration u
X
X
X
X
X
X
X
X
-
-
-
-
-
Abbreviations: AE = adverse event; 
 
COVID-19: = Coronavirus disease 2019; 
d = day; ECG = electrocardiogram;
EGD = esophagogastroduodenoscopy; EGE = eosinophilic gastroenteritis; 
EGID = eosinophilic gastrointestinal disorder;
ePRO = electronic patient-reported outcome; 
 ET = Early Termination; FCBP = female of childbearing potential; 
 
 HIV = human immunodeficiency virus; 
 IP = investigational product; IWRS = Interactive Web 
Response System; OLE = Open-label Long-term Extension;
 
 
PK = pharmacokinetic(s); PRO = electronic patient-reported outcome; SAE = serious adverse event; 
 
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
75
 
 
 
 
a. The assessments performed at the Induction Phase Week 16 Visit will also serve as the data for the first visit of the Maintenance Phase (Maintenance Phase
Week 16 is equivalent to Induction Phase Week 16) and do not need to be repeated specifically for the Maintenance Phase. If the first visit of the Maintenance
Phase does not occur at the Induction Week 16 Visit, an assessment of concomitant medications and AEs/SAEs will be performed, and a urine pregnancy test
(FCBP only) will be performed only if it has been more than 30 days since the last test. A + 4 day allowance (in addition to the Visit 8 window of ± 3 days) for
the scheduling of the EGD and investigator assessment of subject suitability for entry to Maintenance may be used if needed. All assessments are to be performed
prior to IP administration. Subjects should begin the Maintenance Phase within ≤14 days from the final dosing in the Induction Phase.
b. An EGE Flare Assessment Visit should be scheduled as close as possible to the time that an EGE flare is suspected.
c. Subjects who prematurely discontinue the study during the Maintenance Phase will be asked to complete an Early Termination Visit and then an Interim and a
Final Safety Follow-up Visit at 8 weeks and at 16 weeks, respectively, after final IP administration for the assessment of safety and clinical status. Early
Termination procedures performed at the EGE Flare Assessment Visit do not need to be repeated for subjects who are discontinuing the study prematurely due
to an EGE flare.
d. Subjects who complete the Maintenance Phase and do not continue IP administration (in the OLE Phase) will be asked to complete the Interim 8-week Safety
Follow-up Visit (8 weeks after final IP administration; at Week 55 for subjects who complete the Maintenance Phase) and the Final 16-week Safety Follow-up
Visit (16 weeks following final IP administration; at Week 63 for subjects who complete the Maintenance Phase) for assessment of safety and clinical status.
For subjects exiting the study before completing the Maintenance Phase, these visits should occur at 8 and 16 weeks following the last dose of IP (ie, visits may
occur before Week 55 and 63). However, subjects who are permanently discontinued from IP and continue study participation will return for the Interim and
Final Safety Follow-up Visits 8 and 16 weeks after their last study visit instead of their last dose of IP (eg, Week 48 or the ET Visit).
e. Pre-dose collection except for both Safety Follow-up Visits (if applicable), the ET Visit (if applicable), and the EGE Flare Assessment Visit (if applicable).
f. Fasting lipid panel and fasting glucose (instead of random glucose) will only be conducted at Week 16, Week 48, and the ET Visit (if applicable).
g. For females of childbearing potential (FCBP), urine pregnancy tests are required. 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.
h. Complete physical examination to be performed at Maintenance Phase Week 16, Week 48, both Safety Follow-up Visits (if applicable) and at Early Termination
(if applicable). Abbreviated physical examination to be conducted at Week 32.
i. For only subjects aged from 12 to 19 years at the time of signing the ICF/assent), height will be measured at Week 16, Week 32, Week 48, the EGE Flare
Assessment Visit, both Safety Follow-up Visits, and ET Visit in which the EGID severity scoring is scheduled.
l. The Izumo Scale is to be completed weekly (at the same time as much as possible) from Week 16 through Week 48 using a handheld device (ePRO instrument).
For subjects who are required to complete the Safety Follow-up Visits, the Izumo Scale will also be assessed for at least the prior week at each of the 2 Safety
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
76
Follow-up Visits. Subjects will not be able to complete a questionnaire more than 3 days before/after it is due and will not be able to go back and make any 
corrections or changes to the data originally entered.
m.The height obtained at the most recent visit can be used to calculate the EGID severity score for subjects from 12 to 19 years at the time of signing the ICF/assent.
p. Esophagogastroduodenoscopy (EGD) biopsies 
.
q. EGD is required at EGE Flare Assessment Visits to determine if use of rescue therapy is clinically indicated. Alternatively, if endoscopy is conducted as part of 
an emergency department visit or hospitalization for the EGE flare, data should be collected for the EGE Flare Assessment Visit EGD requirement. All attempts 
should be made to collect biopsy samples, and these samples should be sent to the central reader for histologic analysis.
r. EGD is not required at Early Termination Visits that occur before Week 24 of the Maintenance Phase.
s. If a subject meets the rescue criteria detailed in Section 6.4.2.10, the subject can enter the OLE Phase. A subject may be eligible for entry to the OLE Phase 
during the Maintenance Phase.
t. All subjects should be re-randomized via IWRS. However only subjects who are randomized to receive CC-93538 360 mg SC once weekly in the Induction 
Phase will be re-randomized (1:1) to CC-93538 360 mg SC once weekly or CC-93538 360 mg SC once every other week and subjects who are randomized to 
receive matching placebo in the Induction Phase will continue placebo in the Maintenance Phase.
u. Subjects continuing participation in the Maintenance Phase will be given their first dose of IP at the first visit of the Maintenance Phase (ie, the Week 16 
Induction Visit for most subjects). Subjects will then receive weekly doses through Week 47 (ie, a total of 32 doses of IP). For a subject who chooses to proceed 
to the OLE Phase, when a subject’s Week 48 visit and the first visit of the OLE Phase do not occur on the same day, an extra IP will not be dispensed, and IP 
administration will be skipped until entering the OLE Phase.
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
77
Table 6:
Table of Events for the Open-label Long-term Extension (OLE)
Study 
Procedures
Base-
line a
Open-label Long-term Extension Period Year 1
Open-label Long-term Extension Period 
Year 2 and Beyond b
EGE 
Flare 
Asses
s-
ment 
Visitc
OLE-
ET/
EoT
Visitd
Interim 
8-week 
Safety 
Follow-
up 
Visit
Final 
16-
week 
Safety 
Follow-
up 
Visit
Visit Label
OLE 
Visit 
1a, e
OLE 
Visit 2e
OLE 
Visit 3e
OLE 
Visit 4e
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 
Q1
(Year x 
+Wk 13 
[±14d])
Mid-point 
of Year 
(Year x + 
Wk 26 
[±14d])
End of Q3 
(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)
Confirm 
eligibility
X
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Concomitan
t therapy
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AEs/SAEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematology 
and 
chemistry f
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis f
(pre dose)
X
X
-
-
X
-
X
-
X
-
X
X
X
X
X
Urine 
pregnancy 
test (FCBP 
only) g
X
X
X
X
X
X
X
X
X
X
X
-
X
X
X
Physical 
examination
h
X
X
X
X
X
X
X
X
X
X
X
-
X
X
X
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
78
Table 6:
Table of Events for the Open-label Long-term Extension (OLE)
Study 
Procedures
Base-
line a
Open-label Long-term Extension Period Year 1
Open-label Long-term Extension Period 
Year 2 and Beyond b
EGE 
Flare 
Asses
s-
ment 
Visitc
OLE-
ET/
EoT
Visitd
Interim 
8-week
Safety
Follow-
up 
Visit
Final 
16-
week 
Safety 
Follow-
up 
Visit
Visit Label
OLE 
Visit 
1a, e
OLE 
Visit 2e
OLE 
Visit 3e
OLE 
Visit 4e
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 
Q1
(Year x 
+Wk 13
[±14d])
Mid-point 
of Year 
(Year x + 
Wk 26 
[±14d])
End of Q3 
(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)
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum 
antibodies 
to CC-
93538 f, j
X
X
X
X
X
X
X
X
X
X
X
-
X
X
X
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
79
Table 6:
Table of Events for the Open-label Long-term Extension (OLE)
Study 
Procedures
Base-
line a
Open-label Long-term Extension Period Year 1
Open-label Long-term Extension Period 
Year 2 and Beyond b
EGE 
Flare 
Asses
s-
ment 
Visitc
OLE-
ET/
EoT
Visitd
Interim 
8-week
Safety
Follow-
up 
Visit
Final 
16-
week 
Safety 
Follow-
up 
Visit
Visit Label
OLE 
Visit 
1a, e
OLE 
Visit 2e
OLE 
Visit 3e
OLE 
Visit 4e
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 
Q1
(Year x 
+Wk 13
[±14d])
Mid-point 
of Year 
(Year x + 
Wk 26 
[±14d])
End of Q3 
(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)
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
80
Table 6:
Table of Events for the Open-label Long-term Extension (OLE)
Study 
Procedures
Base-
line a
Open-label Long-term Extension Period Year 1
Open-label Long-term Extension Period 
Year 2 and Beyond b
EGE 
Flare 
Asses
s-
ment 
Visitc
OLE-
ET/
EoT
Visitd
Interim 
8-week
Safety
Follow-
up 
Visit
Final 
16-
week 
Safety 
Follow-
up 
Visit
Visit Label
OLE 
Visit 
1a, e
OLE 
Visit 2e
OLE 
Visit 3e
OLE 
Visit 4e
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 
Q1
(Year x 
+Wk 13
[±14d])
Mid-point 
of Year 
(Year x + 
Wk 26 
[±14d])
End of Q3 
(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)
CC-93538
administra-
tion x
X
X
X
X
X
X
X
X
X
X
X
-
-
-
-
Abbreviations: AE = adverse event; 
 
 COVID-19: = 
Coronavirus disease 2019; d = day; 
 EGD = esophagogastroduodenoscopy; EGE = eosinophilic gastroenteritis;
EGID = eosinophilic gastrointestinal disorder;
EoT = End of Treatment; ET = Early Termination; FCBP = 
female of childbearing potential; 
 
 IP = investigational product; OLE = Open-label Long-term Extension; 
 
; Q = Quarter; SAE = serious adverse event; 
 
 
 
 
 Wk = Week
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
81
a All Open-label Long-term Extension (OLE) Day 1 study procedures/assessments will serve as baseline assessments and will be completed prior to dosing. The 
OLE Day 1/Baseline assessments will include the Induction Phase Week 16 Visit assessments, Maintenance Phase Week 48 Visit assessments, or Maintenance 
Phase EGE Flare Assessment Visit and ET Visit assessment, as applicable. Additional OLE baseline assessments not performed at the final Induction Phase
Visit (Week 16), Maintenance Phase Visit (Week 48), or Maintenance Phase EGE Flare Assessment Visit and ET Visit assessment 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 6.3.2. OLE Day 
1/Baseline refers to any visit during which OLE baseline assessments are obtained, including the Induction Phase Week 16 Visit, Maintenance Week 48 Visit, 
Maintenance Phase EGE Flare Assessment Visit and ET Visit or OLE Day 1. Subjects will not be allowed to enroll in the OLE Phase and receive CC-93538 on 
Day 1 if there will be a delay of > 21 days from dosing in the final Induction Phase Visit or the final dosing in the Maintenance Phase unless discussed with the 
Medical Monitor (refer to Section 6.3.2).
b After completion of Week 48 (OLE Visit 7) plus an additional 4 weeks in the OLE Phase (that is, after Week 52 of the OLE Phase), subjects will continue on 
into the second year of the OLE Phase (OLE Year 2 and beyond). During OLE Year 2 and beyond, subjects will attend study visits every 13 weeks (± 14 days) 
for a total of four 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 included in the Quarterly 1 
and 3 Visits.
c An EGE Flare Assessment Visit should be scheduled as close as possible to the time when an EGE flare is suspected.
d Subjects who discontinue study treatment at any time during the OLE will be asked to complete either an OLE-ET Visit, if discontinuation occurs before the 
Quarterly 4 Visit at the end of OLE Year 2 (OLE Week 104), or an OLE-EoT Visit, if discontinuation occurs at or after the Quarterly 4 Visit at the end of OLE 
Year 2 (OLE Week 104). The visit will occur within 2 weeks after the final dose of CC-93538.
e If subject weighing ≥ 30 kg and <40 kg enters the OLE Phase from Week 16 of the Induction Phase or during the Maintenance Phase, the first 3 weekly SC 
doses will be administered in the clinic with confirmation of concomitant medications and AEs, and those subjects will remain in the clinic for at least 1 hour 
following dosing for observation and will be monitored every 2 weeks by the site staff by telephone (but not limited to telephone) between regularly scheduled 
visits until OLE Visit 4 (OLE Week 16) (ie, OLE Week 6 [Day 43 ± 3 days], OLE Week 10 [Day 71 ± 3 days], OLE Week 12 [Day 85 ± 3 days], and OLE 
Week 14 [Day 99 ± 3 days])
f Pre-dose assessment, except for the OLE-ET/EoT Visit, 2 Safety Follow-up Visits and the EGE Flare Assessment Visit (if applicable).
g For females of childbearing potential (FCBPs), urine (or serum) pregnancy test will be performed at OLE Day 1/Baseline and 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 
each study visit, the investigator will counsel FCBP subjects on pregnancy precautions for the duration of the study.
h Complete physical examination is to be performed at OLE Day 1/Baseline, OLE Week 24, OLE Week 48, at the Quarterly 4 Visit, at the OLE-ET/EoT Visit, 
and at the 2 Safety Follow-up Visits; abbreviated physical examination is to be performed at OLE Week 4, Week 8, Week 16, Week 36, and at the Quarterly 1, 
2, and 3 Visits.
i
 
 OLE Week 24, OLE Week 48, OLE Q4 Visits (OLE Year 2 and beyond), the EGE Flare Assessment Visit and OLE-ET/EoT 
Visit in which the EGID severity scoring is scheduled.
j
If anti-drug antibodies (ADAs) are detected, they will be further characterized as to whether the ADAs are neutralizing or not in nature.
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
82
x All subjects will receive weekly open-label CC-93538 360 mg during the OLE Phase. Subjects will be given their first dose of CC-93538 at the OLE 
Day 1 Visit (which could be the same day as the Induction Phase Week 16, the Maintenance Phase Week 48, or ET Visit during the Maintenance Phase). 
Subjects will then receive weekly doses throughout the OLE Phase for as long as the study is active; participation may continue until the subject decides 
to withdraw from the study, the investigator decides to withdraw the subject from the study, or the Sponsor decides to terminate/complete 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 single 2 mL weekly SC injection using the 
360 mg/2 mL 
presentation, after the new 360 mg/2 mL 
 presentation is introduced into the OLE Phase for subjects who did not begin dosing with
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
83
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 
Administration Visit.
 
 
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
84
6
PROCEDURES
Assessments and procedures for the Screening Period and the Induction Phase are outlined in 
Table 4. Assessments and procedures for the Maintenance Phase are outlined in Table 5. For the 
Follow-up Period (Safety Follow-up Visits), assessments and procedures are included in both 
Table 4 and Table 5. Assessments and procedures for the Open-label Long-term Extension Phase 
are outlined in Table 6. Study assessments and procedures are also described in Section 6.1,
Section 6.2, and Section 6.3. The day of administration of the first dose of IP is defined as Day 1
(pre-dose/baseline).
It is recommended that the study visits are scheduled in the morning. Whenever possible, the 
assessment order sequence should remain constant, and assessments 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 
assessments and procedures are performed at every visit):
•
EGE clinical symptom assessment instruments and PROs
•
Spontaneous or solicited AE reporting
•
Vital signs
•
Physical examination
•
Clinical laboratory tests, including blood sampling for the assessment of serum CC-93538 
levels, ADA, 
•
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.
The Izumo Scale will be completed weekly during the Screening, the Induction, the Maintenance 
and the OLE Phases, and for those subjects who are required to complete the Safety Follow-up 
Visits (Section 6.3.1), the Izumo Scale will be assessed at least for the prior week at each of the 2 
Safety Follow-up Visits.
For the purposes of this study, adolescents are defined as subjects aged 12 to 17 years at the time 
of signing the ICF/assent form in Study CC-93538-EG-001 and adults are defined as subjects aged 
2.0
Approved
930196221
2.0
v
Approved
1.0
v
Approved
1.0
v

CC-93538 (BMS-986355)
Protocol CC-93538-EG-001
Celgene International II Sàrl
Protocol CC-93538-EG-001 Amendment 5.0 
Final: 20 Sep 2023
85
18 to 75 years at the time of signing the ICF. 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 completed by adult subjects (The EGID Severity Score is an 
exception, different score scales are used for subjects from 12 to 19 years and subjects ≥ 20 years 
at the time of signing the ICF/assent, respectively).
Any questions regarding the protocol should be directed to the Celgene Medical Monitor or 
designee.
6.1
Screening Period
Screening evaluations will be performed for all subjects to determine study eligibility. These 
evaluations must be completed within 28 days (4 weeks) prior to receiving the first dose of IP 
unless noted otherwise below. Waivers to the protocol will not be granted during the conduct of
this study, under any circumstances.
Screening procedures, as specified in the Table of Events detailed in Table 4, will be performed 
for all subjects to determine study eligibility. All screening procedures must be completed within 
4 weeks prior to receiving the first dose of IP. If there are issues with scheduling the screening 
EGD procedure, the screening window for informed consent and the EGD procedure may be 
extended up to 8 weeks prior to the first dose of IP. However, the EGD may not be performed 
during the last 2 weeks of screening at the same time the electronic PRO (ePRO) will be evaluated 
for the baseline timepoint. In addition, a preliminary assessment of inclusion/exclusion criteria, 
including the intensity of EGE symptoms, should be performed by the investigator before 
scheduling the EGD procedure for subjects. For FCBP subjects who initiate treatment with birth 
control during screening, birth control must be effective by the time the FCBP subject is 
randomized into the study (eg, hormonal contraception should be initiated at least 28 days before 
randomization). If necessary, the randomization/Day 1 Visit may be delayed up to a maximum of 
28 days to achieve the minimum treatment duration. If the Day 1 Visit is delayed, the Medical 
Monitor should be contacted to confirm if any screening assessments (eg, safety laboratories, etc.) 
need to be repeated prior to randomization. All other screening assessments and procedures are to 
be performed by the Principal Investigator or a qualified designee. The ePRO instruments 
including the Izumo Scale,
 
 will be distributed to subjects at the Screening Visit.
After completion of a training module, weekly assessments may be performed starting prior to 
scheduled Day 1 (baseline) for consecutive weeks during the screening period (ie, the Izumo Scale
data collections during screening period are 5 times at maximum [on Day-28, Day-21, Day -14, 
Day -7, and Day 1]). Subjects will not be able to complete a questionnaire more than 3 days 
before/after it is due. Subjects are required to have completed for at least the prior 2 consecutive
weeks of the Izumo Scale data collection on Day 1 (ie, for the final 2 weeks of screening preceding 
Day 1 that are assessed on Day -7 and Day 1) in order to be enrolled in the study.
It is expected that 
 
. A telephone call 
may be made to subjects as a reminder to complete 
 
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. Telephone calls may take place just prior to the beginning of the final 
 
and 
 which serves as the study 
baseline.
Safety laboratory analyses and all assessments will be performed. Screening laboratory values 
must demonstrate subject eligibility, but may be repeated within the screening window, if
necessary.
Written, signed, and dated informed consent/assent from the subject prior to the performance of
any study related procedures must be obtained by the Principal Investigator or designee (refer to
Section 12.3 for further details regarding obtaining subjects’ informed consent/assent). A copy of
the signed informed consent/assent must be given to the subject for his/her records.
The following evaluations will be performed at screening as specified in the Table of Events
(Table 4), after informed consent/assent has been obtained:
•
Assessment of inclusion/exclusion criteria
•
Demographics and baseline characteristics
•
Medical history
•
Prior therapy and concomitant therapy including details of the concomitant use of steroid. The
use of concomitant medication and procedures will be monitored throughout the study. Refer
to Section 8 for prohibited concomitant therapies and permitted concomitant therapies
including stable dose requirements and other restrictions.
•
Adverse event assessment begins when the subject signs the informed consent/assent form.
Throughout the course of the study, every effort must be made to remain alert to possible AEs
or SAEs. Once subjects consent, AEs/SAEs will be recorded at each study visit. Refer to
Section 10 for definitions of AEs/SAEs, monitoring, and reporting. In addition, device (ie,
PFS) failures or malfunctions should be captured, and device related AEs should also be
collected.
•
Hematology, chemistry, coagulation panel, and urinalysis (central laboratory). The following
safety laboratory tests will be performed to assess the safety profile of CC-93538:
−
Hematology: red blood cell (RBC) count, total and differential white blood cell (WBC)
count (basophils, eosinophils, lymphocytes, monocytes, and neutrophils), platelet count,
hemoglobin (hgb), hematocrit (hct), mean corpuscular volume (MCV), mean corpuscular
hemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC)
−
Blood chemistry: indices included at all required chemistry time points are sodium,
potassium, chloride, calcium, magnesium, phosphate, blood urea nitrogen, glucose
(random, at time points not requiring fasting), albumin, alkaline phosphatase, creatinine,
creatine phosphokinase (CPK), ALT/SGPT, AST/SGOT, gamma glutamyltransferase
(GGT), amylase, total bilirubin, direct bilirubin and C-reactive protein (CRP); in addition,
fasting lipid panel (total cholesterol, triglycerides, high-density lipoprotein, and low-
density lipoprotein) and fasting glucose (instead of random glucose) will be performed only
at Day 1, Week 16, Week 48, and the ET Visit (if applicable)
−
Coagulation: prothrombin time (PT), activated partial thromboplastin time (aPTT), and
international normalized ratio (INR)
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−
Urinalysis: leukocytes, specific gravity, bilirubin, blood, glucose, ketones, pH, protein, and 
urobilinogen 
−
The coagulation panel will only be conducted at screening. The hematology, chemistry,
and urinalysis will be performed pre-dose (except for the Safety Follow-up Visit, ET Visit,
and the EGE Flare Assessment Visit if applicable) at screening and the additional time
points outlined in the Table of Events (Table 4, Table 5 and Table 6).
•
Testing for hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV (central laboratory) will 
be performed at screening only.
−
HBV: Hepatitis B surface antigen (HBsAg) screening test and hepatitis B core antibody 
(HBcAb) test will be performed. Subjects who test positive for HBsAg will be excluded 
from the study. For subjects who test positive only for HBcAb, an HBV deoxyribonucleic 
acid (DNA) test must be performed. If the HBV DNA test is positive, the subject will be 
excluded from the study. If the HBV DNA test is negative, the subject will be eligible for 
this study.
−
HCV: HCV antibody (anti-HCV IgG) test will be performed. Subjects testing positive for 
HCV antibody and have a positive confirmatory test (HCV ribonucleic acid [RNA]) will 
be excluded from the study. Subjects with evidence of cleared HCV infection (eg, HCV 
antibody positive subjects who are negative for HCV RNA) and who have not received 
anti-HCV therapy for at least 12 weeks will be eligible for participation.
−
HIV: An HIV antibody test will be performed. Subjects testing positive for HIV will be 
excluded from the study.
•
Testing for tuberculosis (TB) will be performed at screening only. Active TB must be ruled 
out according to local medical practices. Latent TB must be assessed with a TB skin test, 
QuantiFERON Gold test, or other interferon gamma release assay (IGRA) (eg, T-SPOT). 
Subjects with latent TB must have documentation of completed prophylactic treatment by local 
standard of care. Subjects with an indeterminate test result using any IGRA test must be 
discussed for eligibility on a case by case basis by the Sponsor’s Medical Monitor or designee. 
Subjects with latent TB who were only partially treated or who are currently receiving 
prophylactic treatment will not be eligible for randomization.
•
Serum pregnancy test (only for FCBP). A test for the β-subunit of serum human chorionic 
gonadotropin (β-hCG) must be performed at screening in females of childbearing potential. 
Urine (or serum) β-hCG will be performed at Day 1 and at the time points outlined in the Table 
of Events (Table 4, Table 5 and Table 6). In the event of a positive urine test, the subject is not 
to be dosed, and confirmation with a serum pregnancy test should be performed. At screening 
and at each subsequent study visit, the investigator will counsel FCBP subjects on pregnancy 
precautions for the duration of the study.
•
Physical examination: A complete physical examination (including evaluation of heart, lung, 
head and neck, abdomen, neurological assessment, and extremities) 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 4, Table 5 and Table 6). 
•
Height (in centimeters) and weight (in kilograms)
•
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 
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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.
•
Electrocardiogram (ECG): Single 12-lead ECG will be conducted only at the Screening Visit
when the subject is at rest and may be repeated to confirm any abnormal findings.
•
Weekly Izumo Scale questionnaire (Section 6.4.2.1) (at least on Day -7 and Day 1)
(APPENDIX B)
•
EGD with tissue biopsies (Section 6.4.1)
−
Note that 
 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
6.1.1
Additional Information Regarding Safety Laboratory Assessments
Analysis of samples will be conducted by a central laboratory. Details regarding collection of 
samples, shipment of samples, reporting of results, laboratory reference ranges, and alerting 
abnormal values will be supplied to the site before site initiation in a Study Laboratory Manual.
The results of the analysis will be made available to each site by the central laboratory.
Additional and repeat laboratory safety testing may be performed locally at the discretion of the 
investigator. As local laboratory data will not be collected in the 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.
6.1.2
Screening Failures and Rescreening of Potential Subjects
A screen failure is defined as a subject who has given informed consent/assent and failed to meet 
the inclusion and/or exclusion criteria. Subjects who initially fail to meet the inclusion/exclusion 
criteria may be re-screened as per the assessment of the investigator. Subjects who are re-screened 
will be required to be re-consented and have all required Screening Visit procedures performed.
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6.1.2.1
Retesting of Subjects who Develop COVID-19 During the Screening 
Period
Molecular testing for asymptomatic COVID-19 infection is not required in this study. However, 
where local requirements or institutional practice are more restrictive, asymptomatic COVID-19 
screening may be performed locally, to ensure compliance with current local guidance. In addition, 
some subjects may develop suspected or confirmed symptomatic COVID-19 infection, or it may 
be discovered that subjects have asymptomatic COVID-19 infection during the Screening Period.
In such cases, subjects may be considered eligible for the study after meeting all 
inclusion/exclusion criteria related to active infection, and after meeting the following criteria:
•
At least 10 days (20 days for severe/critical illness) have passed since symptoms first appeared 
or positive test result, and
•
At least 24 hours have passed since last fever without the use of fever-reducing medications, 
and
•
Symptoms (eg, cough and shortness of breath) have resolved and 
•
In the opinion of the investigator, there are no COVID-19 sequelae that may place the subject 
at a higher risk of receiving investigational treatment, and 
•
Negative follow-up molecular test for COVID-19 based on institutional, local, and/or regional 
guidelines and/or requirements.
6.2
Induction Phase and Maintenance Phase
On Day 1, prior to randomization in the Induction Phase, the baseline assessments (including 
laboratory assessments), as shown in Table 4, will be completed. The investigator will review all 
available information to confirm subject eligibility.
•
Screening laboratory tests will be used to determine eligibility for randomization with the 
exception of pregnancy tests, which will need to be confirmed by the Day 1 test results.
•
A urine (or serum) pregnancy test must be performed for all FCBP on Day 1 and the results 
reviewed prior to randomization. A negative pregnancy test result must be obtained prior to 
randomization. If the urine pregnancy test result is positive but this is believed to be a false 
positive, the site may perform a stat serum pregnancy test at the local laboratory to confirm 
pregnancy status.
•
Baseline laboratory tests will be performed on Day 1 for comparison with follow-up tests. 
However, the results of these tests will not be available prior to randomization on Day 1.
•
The following instruments will be administered prior to dosing on Day 1 to serve as the 
baseline assessment:
−
Weekly Izumo Scale questionnaire (Section 6.1 and 6.4.2.1) (APPENDIX B)
−
EGID Severity Score (Section 6.4.2.2) (APPENDIX C and APPENDIX D)
 
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After eligibility has been confirmed and baseline assessments have been completed, eligible 
subjects will be randomized to treatment on Day 1. 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 per 
the Table of Events (Table 4 for the Induction Phase and Table 5 for the Maintenance Phase). For 
subjects weighing ≥ 30 kg and <40 kg, the first 3 weekly SC doses will be administered in the 
clinic with confirmation of concomitant medications and AEs, and those subjects will remain in 
the clinic for at least 1 hour following dosing for observation and be monitored every two weeks 
by the site staff by telephone (but not limited to telephone) between regularly scheduled visits until 
Week 16 (ie, Week 6 [Day 43 ± 3 days], Week 10 [Day 71 ± 3 days], and Week 14 [Day 99 ± 3
days]).
Dosage regimen of permitted anti-inflammatory therapy (including concomitant corticosteroid 
treatment; the equivalent of up to 10 mg/day of prednisone) must be kept stable until Week 16. 
Subjects who do not require concomitant treatment are also eligible for this study.
If the reduction of EGE-related symptoms is observed at/after Week 16, the investigator should 
begin tapering the dosage regimen of concomitant corticosteroids treatment after Week 16. The 
dose reduction should be 2.5 mg / week (as the equivalent of prednisone). If the symptoms worsen 
after tapering of the dosage regimen of concomitant corticosteroid treatment, the dose can be 
increased until the baseline dosage at the Induction Phase.
For the Maintenance Phase, eligible subjects will be re-randomized to treatment on Week 16. The 
assessments performed at the Week 16 Visit (Visit 8) of the Induction Phase will also serve as the 
data for the Maintenance Phase Week 16 Visit (Visit 8) and do not need to be repeated specifically 
for the Maintenance Phase. If the Maintenance Phase Week 16 Visit, the first day of the 
Maintenance Phase, does not occur at the Induction Phase Week 16 Visit (Visit 8), an assessment 
of concomitant medications and AEs/SAEs will be performed, and a urine pregnancy test (in FCBP 
only) will be conducted if it has been more than 30 days since the last test. The investigator will 
confirm subjects meet the criteria to enter the Maintenance Phase according to Section 6.4.2.11. A 
+ 4-day allowance (in addition to the Visit 8 window of ± 3 days) for the scheduling of the EGD 
and investigator assessment of subject suitability for entry to the Maintenance Phase is available 
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if needed. Subjects should begin the Maintenance Phase within ≤14 days from the final dosing in 
the Induction Phase.
If subjects are out of window for their Week 16 dose due to use of the additional +4 day window 
for the EGD, subjects should skip the Week 16 dose and take the Week 17 dose which will be their 
first Maintenance Phase dose.
The following will be performed during the Induction Phase and Maintenance Phase Treatment 
Periods as specified in the Table of Events detailed in Table 4 and Table 5:
•
Confirm eligibility (for the Maintenance Phase): If the results of the gastric/duodenal eos count
will be disclosed during the Induction Phase, the subject is to be discontinued from the study
and will not be allowed to enter the Maintenance Phase.
•
Assessment of inclusion/exclusion criteria to confirm eligibility (Day 1 only)
•
Concomitant therapy
•
Assessment of AEs/SAEs
•
Hematology, chemistry, and urinalysis
•
Urine pregnancy test (only for FCBP)
•
Physical examination
•
Vital signs
•
Serum antibodies to CC-93538
•
Serum CC-93538 PK assessment
•
Pharmacogenetic assessment, if applicable per government and local regulations, will be
collected one time at Day 1 in subjects who provide consent (note, the sample may be obtained
at any subsequent Induction Phase visit
•
Weekly Izumo Scale questionnaire (APPENDIX B)
•
EGID Severity Score (APPENDIX C and APPENDIX D)
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•
EGD with tissue biopsies
•
Randomization via IWRS (Day 1 and Week 16)
•
Entry to the Maintenance Phase assessment (only at Induction Phase Week 16)
•
Entry to the OLE Phase assessment (at Induction Phase Week 16, during the Maintenance
Phase or at Maintenance Phase Week 48)
•
IP administration
Telephone call reminders may take place before the 28-day collection for the daily assessment 
period preceding the Week 16, Week 32 and Week 48 endpoint assessments (ie, just prior to Weeks 
12, 28 and 44) and before the collection period preceding the 2 Safety Follow-up Visits, if 
applicable. A telephone contact may be made at other time points as part of ongoing surveillance.
Refer to Section 6.4, for a description of the efficacy assessments conducted throughout the study.
6.2.1
EGE Flare Assessment Visit
Subjects with a worsening of EGE symptoms during the study, either in the Induction Phase or 
Maintenance Phase will be required to complete the EGE Flare Assessment Visit as shown in the 
Table of Events (Table 4, Table 5 and Table 6). Subjects with increased signs and symptoms of 
EGE are instructed to contact the investigator and/or study staff to determine if an EGE Flare 
Assessment Visit is warranted. An EGE Flare Assessment Visit should be scheduled as close as 
possible to the time that an EGE flare is suspected.
Any worsening of EGE symptoms during study participation will be documented as an EGE flare. 
See Section 6.4.2.10 for the protocol definition of EGE flare and EGE Flare Assessment Visit
details.
In the event that subjects discontinue the study prematurely due to an EGE flare, the ET Visit or 
the OLE-ET/EoT Visit will also be completed, but procedures performed at the EGE Flare 
Assessment Visit do not need to be repeated for the ET visit or the OLE-ET/EoT Visit.
If subjects had an EGD performed for an EGE flare assessment during the Induction (prior to Week 
16) or Maintenance (prior to Week 48) Phases, an EGD will also be performed at Week 16 or
Week 48, respectively. However, an exception will be made if in the investigator’s judgment the
EGE flare assessment occurred too close to Week 16 or Week 48 such that it is considered unsafe
to perform another EGD within this short interval. In these cases, a discussion with the Medical
Monitor will take place well in advance of the Week 16 or Week 48 Visit.
The following evaluations will be performed as specified in Table 4, Table 5, and Table 6:
•
Concomitant therapy
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•
Assessment of AEs/SAEs
•
Hematology, chemistry, and urinalysis*
•
Vital signs
•
EGID Severity Score (APPENDIX C and APPENDIX D)
•
EGD with tissue biopsies**
Refer to Section 6.4 for a description of the efficacy assessments conducted throughout the study.
6.2.2
Early Termination Visit
For subjects who discontinue the Induction Phase and the Maintenance Phase of the study 
prematurely for any reason (ie, subjects who do not complete Week 48) or enter the OLE Phase 
during the Maintenance Phase (if a subject meets the rescue criteria detailed in Section 6.4.2.10, 
the subject can enter the OLE Phase), every attempt should be made to complete the assessments 
detailed in the ET Visit conducted as close as possible to the time of study discontinuation or of 
the visit determining entrance to the OLE Phase from the Maintenance Phase. The ET Visit should 
be completed within 2 weeks after the final CC-93538 dose. If study discontinuation or the visit 
determining entrance to the OLE Phase from the Maintenance Phase occurs at the regularly 
scheduled visit (eg, Induction Phase Week 12 or Maintenance Phase Week 32), the ET Visit and 
all corresponding ET Visit procedures should be conducted (Table 4 and Table 5). In addition, 
subjects who discontinue the study should return for the Safety Follow-up Visit (Section 6.3.1). 
Subjects who complete the Induction Phase Week 16 Visit but do not continue in the Maintenance 
Phase or the OLE Phase should complete the Week 16/ET Visit and return for the Interim 8-week 
and Final 16-week Safety Follow-up Visits at Week 23 and Week 31, respectively (Section 6.3.1). 
Subjects who complete the Induction Phase and enter the OLE Phase should complete the Week 
16/ET Visit; these subjects do not need to return for the 2 Safety Follow-up Visits. Assessments 
conducted at the Week 16 Visit do not need to be repeated. Subjects who do not complete 
∗ 
Note that these samples do not need to be a pre-dose draw unless the subject is expected to dose later that 
day. 
∗∗
Note that EGD is required at EGE Flare Assessment Visits to determine if use of rescue therapy is
clinically indicated. Alternatively, if an endoscopy is conducted as part of an emergency department visit or
hospitalization for the EGE flare, medical record source data should be collected for the EGE Flare Assessment
Visit EGD requirement. In addition, all attempts should be made to collect biopsy samples, and these samples
should be sent to the central reader for histologic analysis.
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Maintenance Phase Week 48 but enter the OLE Phase (Section 3.1.6) do not need to return for the 
2 Safety Follow-up Visits. Subjects who complete the Maintenance Phase Week 48 but do not 
continue in the OLE Phase should return for the Interim 8-week and Final 16-week Safety Follow-
up Visits at Week 55 and Week 63, respectively. For subjects who are discontinuing the study 
prematurely due to an EGE flare, ET procedures performed at the EGE Flare Assessment Visit do 
not need to be repeated.
The following evaluations will be performed as specified in (Table 4 and Table 5):
•
Concomitant therapy
•
Assessment of AEs/SAEs (monitored through 16 weeks after the last dose of IP or the Final
Safety Follow-up Visit, whichever is longer)
•
Hematology, chemistry, and urinalysis
•
Pregnancy test (only for FCBP)
•
Physical examination
•
Vital signs
•
Serum antibodies to CC-93538
•
Serum CC-93538 PK assessment
•
Weekly Izumo Scale questionnaire (APPENDIX B)
•
EGID Severity Score (APPENDIX C and APPENDIX D)
•
EGD with tissue biopsies*
∗Note that EGD is not required for ET Visits occurring before Week 8 in the Induction Phase or before Week 24 in
the Maintenance Phase.
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Refer to Section 6.4 for a description of the efficacy assessments conducted throughout the study.
6.3
Follow-up Period 
6.3.1
Safety Follow-up (Interim 8-week and Final 16-week)
All subjects will be followed for 16 weeks after the last dose of IP or until the Final Safety Follow-
up Visit, whichever is longer, for AE reporting, as well as SAEs made known to the investigator
at any time thereafter that are suspected of being related to IP, as described in Section 10.2.3.
In the Induction Phase, subjects who discontinue from the study prior to completing Week 16, or 
subjects who complete Week 16 and do not enter the Maintenance Phase or the OLE Phase will 
return for an Interim and a Final Safety Follow-up Visit at 8 and 16 weeks, respectively, after final 
IP administration (at Week 23 and Week 31 for subjects completing the Induction Phase) for the 
assessment of safety and clinical status after exiting the study. However, subjects who are 
permanently discontinued from IP and continue study participation in order to complete safety and 
efficacy assessments in the phase of the study that permanent discontinuation from IP occurs 
(according to Section 11.1) will return for the Interim and Final Safety Follow-up Visits 8 and 16 
weeks after their last study visit instead of their last dose of IP (eg, Week 16 or the ET Visit). 
Assessments should be performed in accordance with the Table of Events (Table 4). Subjects who 
continue participation in the Maintenance Phase or the OLE Phase will not return for the 2 Safety 
Follow-up Visits.
In the Maintenance Phase, subjects who discontinue from the study prior to completing Week 48 
but do not enroll in the OLE Phase or complete Week 48 but do not enroll in the OLE Phase will 
also return for an Interim and a Final Safety Follow-up Visit at 8 and 16 weeks, respectively after 
final IP administration (at Week 55 and Week 63 for completers of the Maintenance Phase) for the 
assessment of safety and clinical status after exiting the study. However, subjects who are 
permanently discontinued from IP and continue study participation in order to complete safety and 
efficacy assessments in the phase of the study that permanent discontinuation from IP occurs 
(according to Section 11.1) will return for the Interim and Final Safety Follow-up Visits 8 and 16 
weeks after their last study visit instead of their last dose of IP (eg, Week 48 or the ET Visit). 
Assessments to be performed are presented in the Table of Events (Table 5). Subjects who 
continue participation in the OLE Phase will not return for the 2 Safety Follow-up Visits.
In the OLE Phase (Section 6.3.2), all subjects should return for an Interim and a Final Safety 
Follow-up Visit at 8 and 16 weeks, respectively after final IP administration. Assessments to be 
performed are presented in the Table of Events (Table 6).
The following evaluations will be performed as specified in Table 4, Table 5 and Table 6:
•
Concomitant therapy
•
Assessment of AEs/SAEs (monitored through 16 weeks after the last dose of IP or the Final 
Safety Follow-up Visit, whichever is longer)
•
Hematology, chemistry, and urinalysis
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•
Pregnancy test (only for FCBP)
•
Physical examination
•
Vital signs
•
Serum antibodies to CC-93538
•
Serum CC-93538 PK assessment
•
Weekly Izumo Scale questionnaire at least for the prior week (7 days) period preceding each
of the 2 Safety Follow-up Visits (for Safety Follow-up of the Induction Phase and the
Maintenance Phase)
•
EGID Severity Score (for Safety Follow-up of the Induction Phase and the Maintenance Phase)
Refer to Section 6.4 for a description of the efficacy assessments conducted throughout the study.
6.3.2
Open-label Long-term Extension (OLE) Phase
The OLE Day 1/Baseline assessments shown in Table 6 will be completed prior to the first dose 
of CC-93538 in the OLE Phase. OLE Day 1/Baseline refers to any visit during which OLE baseline 
assessments are obtained, including the following visits from: Induction Phase Week 16 Visit or 
the Maintenance Phase Week 48 Visit, or the ET Visit during the Maintenance Phase. Transition 
to the OLE Phase should occur for most subjects on the same day as the Induction Phase Week 16
Visit, the Maintenance Phase Week 48 Visit or the ET Visit during the Maintenance Phase. 
Subjects entering the OLE Phase will not complete the Safety Follow-up Visits after the Induction 
Phase or the Maintenance Phase. Subjects will not be eligible to enroll in the OLE Phase and 
receive CC-93538 on OLE Day 1 if there will be a delay of > 21 days from dosing in the final 
Induction Visit or the final dosing in the Maintenance Phase. The investigator will review all 
available information to confirm that the subject continues to meet all study enrollment criteria 
and complete the additional Day 1 activities for confirmation of eligibility. 
The following evaluations/activities will be performed as specified in Table 6:
•
Confirm eligibility: If the results of the gastric/duodenal eos count will be disclosed during the
Induction Phase, the subject is to be discontinued from the study and will not be allowed to
enter the OLE Phase.
•
The OLE baseline assessments will include those conducted for the Induction Phase Week 16
Visit, Maintenance Phase Week 48 Visit or Maintenance Phase ET Visit, as applicable.
Additional OLE baseline assessments not performed at the final Induction Phase Visit (Week
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16), Maintenance Phase Visit (Week 48), or Maintenance Phase ET Visit 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 schedule of events 
(Table 6). Subjects will not be allowed to enroll in the OLE study and receive CC-93538 on 
Day 1 if there will be a delay of > 21 days from final dosing in the Induction Phase or the 
Maintenance Phase unless discussed with the Medical Monitor.
•
The EGD procedure should not be repeated at the OLE Day 1 Visit, as long as this assessment 
was conducted at the final Induction Phase Visit (Week 16), Maintenance Phase Visit (Week 
48), or Maintenance Phase ET Visit.
•
If OLE Day 1 is not on the same day as the final Induction Phase (Week 16), Maintenance 
Phase (Week 48) Visit or ET Visit during the Maintenance Phase, a urine (or serum) β-hCG 
pregnancy test (FCBP only) must be performed on OLE Day 1 and the results reviewed on 
OLE Day 1 prior to the first open-label OLE CC-93538 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.
•
If subjects had an EGD performed for an EGE flare assessment during the Induction (prior to 
Week 16) or Maintenance (prior to Week 48) Phases, an EGD will also be performed at Week 
16 or Week 48, respectively. However, an exception will be made if in the investigator’s 
judgment the EGE flare assessment occurred too close to Week 16 or Week 48 such that it is 
considered unsafe to perform another EGD within this short interval. In these cases, a 
discussion with the Medical Monitor will take place well in advance of the OLE Day 1 Visit.
After baseline assessments have been completed, eligible subjects will receive CC-93538 360 mg 
in an open-label manner. The first 3 SC weekly doses will be administered in the clinic. Subjects 
will remain in the clinic for at least 30 minutes following dosing for observation. 
If a subject weighing ≥ 30 kg and < 40 kg enters the OLE Phase from Week 16 of the Induction 
Phase or during Maintenance Phase, the first 3 weekly SC doses will be administered in the clinic
with confirmation of concomitant medications and AEs, and those subjects will remain in the clinic 
for at least 1 hour following dosing for observation and be monitored every 2 weeks by the site 
staff by telephone (but not limited to telephone) between regularly scheduled visits until OLE 
Week 16 (ie, OLE Week 6 [Day 43 ± 3 days], OLE Week 10 [Day 71 ± 3 days], OLE Week 12
[Day 85 ± 3 days], and OLE Week 14 [Day 99 ± 3 days]).
Subsequent visits, assessments and procedures will be performed as shown in Table 6.
Following OLE Day 1, in the first year of the OLE Phase (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 Phase (that is, after Week 52 in the OLE Phase), 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 four 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 included in Quarterly 1 and 3 Visits. The 
time points for these visits are as follows:
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•
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 evaluations will be performed during the OLE Phase as specified in the Table 6:
•
Concomitant therapy
•
Assessment of AEs/SAEs (monitored through 16 weeks after the last dose of IP or the Final 
Safety Follow-up Visit, whichever is longer). Refer to Section 10 for definitions of AEs/SAEs, 
monitoring, and reporting. In addition, 
/PFS device failures or malfunctions should be 
captured, and device-related AEs should also be collected.
•
Hematology, chemistry, and urinalysis
•
Pregnancy test (only for FCBP)
•
Physical examination
 
 
•
Vital signs
•
Serum antibodies to CC-93538
•
Serum CC-93538 PK assessment
•
Weekly Izumo Scale questionnaire
•
EGID Severity Score
 
 
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•
EGD with tissue biopsies*
•
CC-93538 administration
Telephone call reminders may take place before the 28-day collection period for daily assessment
preceding the OLE Week 24, OLE Week 36 and OLE Week 48 endpoint assessments (ie, just prior 
to OLE Weeks 20, 32 and 44), if applicable. A telephone contact may be made at other time points 
as part of ongoing surveillance.
Refer to Section 6.4 for a description of the efficacy assessments conducted throughout the study.
6.3.2.2
OLE - Early Termination Visit/End of Treatment: Visit
For subjects who discontinue the OLE Phase of the study for any reason, the assessments detailed 
in the OLE-ET Visit/EoT Visit should be completed within 2 weeks after the final CC-93538 dose 
(Table 6). The OLE-ET Visit will be completed if discontinuation occurs before the Quarterly 4 
Visit at the end of OLE Year 2 (OLE Week 104); the OLE-EoT Visit will be completed if 
discontinuation occurs at or after the Quarterly 4 Visit at the end of OLE Year 2 (OLE Week 104).
If the OLE-EoT Visit occurs at the scheduled Quarterly 4 Visit at the end of OLE Year 2 (OLE 
Week 104), the subject will complete all assessments required for each of the 2 visits collectively 
                                                       
∗Note EGD is required for ET Visits occurring at or before OLE 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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(ie, assessments do not need to be repeated). In addition, these subjects should return for the 
Interim and Final Safety Follow-up Visits (Section 6.3.1).
The following evaluations will be performed as specified in the Table 6:
•
Concomitant therapy
•
Assessment of AEs/SAEs
•
Hematology, chemistry, and urinalysis
•
Urine pregnancy test (only for FCBP)
•
Physical examination
•
Vital signs
•
Serum antibodies to CC-93538
•
Serum CC-93538 PK assessment
•
Weekly Izumo Scale questionnaire (Section 6.4.2.1) (only if the visit occurs before or at the
OLE Week 48)
•
EGID Severity Score (only if the visit occurs before or at the OLE Week 48)
•
EGD with tissue biopsies*
Refer to Section 6.4 for a description of the efficacy assessments conducted throughout the study.
* Note EGD is required for ET Visits occurring at or before OLE 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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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 eos count will be read blinded to treatment allocation at a centralized 
reading facility. Biopsy specimens will be sent to the centralized reading facility, and with the 
exception of screening, results of the centrally read gastric/duodenal eos count will be blinded to
investigative sites during the Induction Phase and the Maintenance Phase. For the OLE Phase, 
biopsy results on OLE Day 1/Baseline EGD only will be read blinded to treatment allocation and 
results will also be blinded to investigative sites since this will be same with the EGD conducted 
either at Week 16 of Induction Phase, during the Maintenance Phase or at Week 48 of Maintenance 
Phase. A local histologic assessment of EGD biopsy samples should not be performed during the 
Induction Phase and the Maintenance Phase, unless required for safety reasons (eg, severe EGE 
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 processing, storage, and shipping will be provided in a separate Study Laboratory 
Manual.
Endoscopic procedures will be performed as follows:
•
EGD will be performed at the time points specified in the Table of Events (Table 4, Table 5
and Table 6).
Note that 
 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.
•
Gastric/duodenal biopsies should be obtained from the following:
Stomach
−
A set of 4 specimens from separate areas of the gastric antrum (2 to 5 cm proximal to the
pylorus)
−
A set of 4 specimens from separate areas of the gastric corpus (two from the proximal lesser
curvature and two from the greater curvature)
−
Up to 1 extra specimen may be collected if there are any additional areas of interest at the
judgement of the investigator (if required)
−
A count of ≥30 eos/hpf in at least 5 hpfs will be considered diagnostic of EG.
Duodenum
−
4 fragments of duodenal mucosa from the second and third part of the duodenum.
−
Up to 1 extra specimen may be collected if there are any additional areas of interest at the
judgement of the investigator (if required)
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−
A count of ≥30 eos/hpf in at least 3 hpfs will be considered diagnostic of EGE.
•
All subsequent biopsies should be obtained from the same levels as the screening biopsies (ie,
stomach and duodenum) maintaining consistency throughout the study.
•
Biopsy samples must be obtained ideally from the areas with the most prominent visible
abnormalities. For example, if 2-bite biopsies are being obtained, a minimum total of 26 biopsy
fragments (from 2 separate 2-bite biopsies) would be obtained from each level.
•
The screening EGD must be performed within 8 weeks prior to Day 1. The investigator must
document all treatments received at the time of the EGD and biopsy (for any indication)
through Day 1, and the subject must not have received any new treatment that might affect
EGE since the time of EGD according to protocol requirements (see Section 8). Subjects
should not undergo the screening EGD during the 14-day period just prior to baseline when
the final 2 weeks of the screening the Izumo Scale is collected.
•
Histologic analysis of the gastric/duodenal biopsy samples for any study-specific assessments
will be performed by a central laboratory including enumeration of eos count (peak eos
count/hpf) and by analysis of Hematoxylin and eosin (H&E) stained biopsies and gastric
biopsies will be graded using the Sydney System on inflammation, metaplasia, atrophy, and
reactive gastropathy. The Marsh Scale Classification will be used to grade duodenal samples.
•
Histologic analysis includes confirmation of absence of H. pylori for gastric biopsies. A highly
sensitive monoclonal immunohistochemical stain will be used. If negative, then the subject can
participate in the study.
6.4.2
Clinical Symptoms of EGE
6.4.2.1
Izumo Scale Questionnaire
An electronic version of the PRO questionnaire (APPENDIX B) will be completed weekly by the 
subject throughout the study. The Izumo Scale questionnaire assesses the comprehensive 5 
different GI symptom domains during the past week and consists with 15 weekly questions (3 
questions per 1 domain):
•
Heartburn Symptoms domain (Questions 1 through 3)
•
Gastric Pain Symptoms domain (Questions 4 through 6)
•
Stomach Heaviness Symptoms domain (Questions 7 through 9)
•
Constipation Symptoms domain (Question 10 through 12)
•
Diarrhea Symptoms domain (Questions 13 through 15)
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Each question is scored on a scale of “0 = No trouble at all” to “5 = Can't stand it,” and one 
symptom domain is scored from 0 to 15, with higher values indicating greater symptom severity. 
Total score is the sum of 5 domains and ranges from 0 to 75.
Three of these 5 domains (Gastric Pain Symptoms domain [Questions 4 through 6], Stomach 
Heaviness Symptoms domain [Questions 7 through 9] and Diarrhea Symptoms domain [Questions
13 through 15]) are Symptoms of Interest for EGE.
The Izumo Scale Questionnaire was developed in order to evaluate the overall gastrointestinal 
symptoms and in Japanese as original language (Furuta, 2009). This is written in easy-to-
understand terms in Japanese, and has verified the usefulness by measuring the correlation 
with Gastrointestinal Symptom Rating Scale (Svedlund, 1988, Dimenäs, 1995) and the Visual 
analog scale (VAS) of each symptom in Japanese patients with Functional gastrointestinal 
disorders (FGIDs) whose symptoms are similar to EGE.
On investigation of 170 Japanese patients with gastrointestinal symptoms, the average scores
of Symptoms of Interest (Gastric Pain Symptoms domain, Stomach Heaviness Symptoms domain, 
and Diarrhea Symptoms domain) on patients with interference with daily activities were 6.17/15, 
5.72/15, and 7.36/15, respectively. On the other hand, the average scores of Symptoms of Interest 
on patients without interference with daily activities were 1.96/15, 2.37/15, and 2.25/15 (Furuta,
2009). Based on this knowledge, 4/15 for each three domains is set as the threshold for inclusion
criteria and clinical responder in this study.
Subjects will complete the Izumo Scale questionnaire weekly during the Screening Period via a 
handheld device for at least the 2 consecutive weeks before the IP administration on Day 1 (ie, for 
the final 2 weeks of screening preceding Day 1 that are assessed on Day -7 and Day 1). Every 
effort should be made to enhance subject adherence to the Izumo Scale Questionnaire completion 
and limit the amount of missing data, which is critical to ensure interpretability of the Izumo Scale
assessment in this study. For example, ePRO instrument’s reminder alarms will allow subjects to 
select the timing for their alarm within a standardized window (at the same time as much as 
possible) of weekly completion of questionnaire, and ongoing surveillance of weekly completion 
data will also occur in order to correct any issues as close to real time as possible. 
Subjects will not be able to complete a questionnaire more than 3 days before/after it is due and 
will not be able to go back and make any corrections or changes to the data originally entered. This 
information will be automatically captured and maintained in the ePRO system of the electronic 
data capture system (EDC).
The Izumo Scale Questionnaire will be administered at the same time weekly as much as possible
via an ePRO instruments from Day 1 through Week 48 (through the duration of the Induction and 
Maintenance Phases) of the study, through the ET Visit (if applicable), and first year of the OLE 
Phase and at least for the prior week period (7 days) preceding each of the 2 Safety Follow-up 
Visits (if applicable) according to the Table of Events (Table 4, Table 5, and Table 6).
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6.4.2.2
EGID Severity Score
Japanese Society of Pediatric Allergy and Clinical Immunology published guidelines of
“Eosinophilic Gastrointestinal Disease Clinical Practice Guidelines for Infants and Adults” in 2020. 
EGID Severity Score has been proposed as the severity classification to define the criteria for 
designated intractable diseases in Japan and is included in this guideline (Eosinophilic 
Gastrointestinal Disease Study Group, Ministry of Health, Labour and Welfare, 2021).
There are 2 forms of EGID Severity Score; for patients ≥ 20 years old (APPENDIX C) and for 
patients from 2 to 19 years old (APPENDIX D).
The EGID scoring tables used in this study refer to the ones shown in "Eosinophilic Gastro-
Intestinal Disorder" disclosed by Japan Intractable Diseases Information Center.
The EGID Severity Scores are assessed by the investigator. The EGID Severity Score for patients 
≥ 20 years old assess the intensity and the frequency of 6 different symptoms (vomiting, dysphagia, 
anorexia, abdominal pain, diarrhea, bloody stool), 2 clinical laboratory tests (albumin, eos ratio of 
peripheral blood cells) and 2 medical history items (history of surgery and use of systemic 
corticosteroid or immunosuppressives). The score ranges from 0 to 82 and the higher the score, 
the greater the severity. A score of ≥ 40 is considered as severe, a score of 15 to 39 as moderate 
and a score of ≤ 14 score as mild. 
The EGID Severity Score for patients from 2 to 19 years old also assesses 6 different symptoms 
(vomiting, dysphagia, anorexia, abdominal pain, diarrhea, bloody stool), 2 clinical laboratory tests 
(albumin, eos ratio of peripheral blood cells) and general condition, 
. 
The score ranges from 0 to 100 and the higher the score, the greater the severity. A score of ≥ 40 
is considered as severe, a score of 15 to 39 as moderate and ≤ 14 score as mild.
The EGID Severity Score will be assessed according to the time points detailed in the Table of 
Events (Table 4, Table 5, and Table 6).
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6.4.2.10
Worsening of EGE Symptoms, EGE Flare, and the EGE Flare 
Assessment Visit
Subjects with a worsening of EGE symptoms during the study, either in the Induction Phase, 
Maintenance Phase, or the OLE Phase will be required to complete the EGE Flare Assessment 
Visit as shown in the Table of Events (Table 4, Table 5, and Table 6). Subjects with increased 
signs and symptoms of EGE are instructed to contact the investigator and/or study staff to 
determine if an EGE Flare Assessment Visit is warranted.
•
Worsening of EGE symptoms is defined as continuous worsening of symptoms for 2 
consecutive visits (4 weeks apart) compared to baseline, measured by the weekly Izumo Scale 
score (≥ 4 weeks of no change from baseline or ≥ 4 weeks of worsening from baseline). 
An EGE Flare Assessment Visit including safety and efficacy evaluations can occur at any time 
during the study. An EGD may be required at the EGE Flare Assessment Visit to determine if use 
of rescue therapy is clinically indicated. Alternatively, if endoscopy is conducted as an intervention 
during an emergency department visit or hospitalization for a worsening of EGE symptoms or 
flare, medical record source data including details of the endoscopic procedure should be collected 
for the EGE Flare Assessment Visit EGD requirement. In addition, all attempts should be made to 
collect biopsy samples, and these samples should be sent to the central reader for histologic 
analysis. The results of the centrally read gastric/duodenal eos count will be blinded to 
investigative sites with the exception of screening during the Induction Phase and the Maintenance 
Phase. If the results of the gastric/duodenal eos count are required to determine the need for 
emergent rescue therapy, the results of the gastric/duodenal eos count will be disclosed as long as 
the investigator requires the result. If the results of the gastric/duodenal eos count will be disclosed 
in the Induction Phase, the subject is to be discontinued from the study and will not be allowed to 
enter either the Maintenance Phase or the OLE Phase. (See Section 3.1.6.)
The investigator will confirm if the worsening of EGE symptoms requires rescue therapy and,
thus, is deemed a severe EGE flare according to the following protocol definitions.
Any worsening of EGE symptoms during study participation will be documented as an EGE flare.
•
A severe EGE flare is defined as any worsening of EGE symptoms including a high intensity 
episode resulting in an emergency department visit or hospitalization, with need for rescue 
therapy (eg, including but not limited to concomitant corticosteroid therapy over the baseline 
dose), or a worsening of EGE symptoms for 2 consecutive visits (4 weeks apart) resulting in 
the need for rescue therapy.
•
A mild to moderate EGE flare is defined as any worsening of EGE symptoms without the need 
for rescue therapy. Concomitant use of systemic corticosteroid therapy with or under the 
baseline dose of concomitant corticosteroid treatment is not considered as rescue therapy.
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During the OLE Phase, subjects who demonstrate a persistent lack of improvement or worsening 
of EGE 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.
The ET visit or the OLE-ET/EoT procedures performed at the EGE Flare Assessment Visit do not 
need to be repeated for subjects who discontinue the study prematurely due to an EGE flare.
Subjects who are discontinued from the Induction Phase, the Maintenance Phase or the OLE Phase 
will be asked to complete an ET visit or an OLE-ET/EoT Visit (Section 6.2.2 and Section 6.3.2.2)
and the 2 Safety Follow-up Visits (Section 6.3.1).
6.4.2.11
Entry to Maintenance Phase
Following completion of Week 16 of the Induction Phase, subjects will be eligible for entry into
the Maintenance Phase if none of the conditions listed below are met, and based on investigator
clinical judgement, it is in the best interest of the subject to continue study participation. Subjects 
who do not qualify for entry to the Maintenance Phase will be eligible for participation in the OLE 
Phase, unless permanent discontinuation from IP has occurred. The following are conditions that 
will exclude subjects from entry to the Maintenance Phase:
•
Subjects with a severe EGE flare as described in Section 6.4.2.10
•
Subjects who demonstrate a worsening of EGE symptoms prior to Week 16 (continuous
worsening of symptoms for 2 consecutive visits [4 weeks apart]) at Week 16, as described in
Section 6.4.2.10
•
Subjects who demonstrate any other significant findings that, in the opinion of the investigator,
could potentially disqualify a subject from entering the Maintenance Phase must be assessed
in conjunction with the Medical Monitor to determine, if the subject is eligible for participation
in the OLE Phase, when a subject wants or the investigator considers it appropriate
•
Subjects who are permanently discontinued from IP during the Induction Phase (before or at
Week 16), and these subjects will not be eligible for participation in the OLE Phase (see
Section 11.1)
•
In addition, for subjects who meet the following condition during the first 16 weeks of
treatment (and without a severe EGE flare), a discussion with the Medical Monitor will be
required before entry into the Maintenance Phase:
−
Subjects with any protocol-prohibited use of or change to diet (eg, steroids over baseline
dose, food elimination) or medication which will impact efficacy assessment for CC-93538
(as determined through consultation with the Medical Monitor) will be excluded from entry
to the Maintenance Phase
By contrast, subjects requiring concomitant systemic corticosteroids for an indication other than
EGE may be eligible for entry to the Maintenance Phase if the duration of therapy is no more than 
10 days and use does not occur within the 6 weeks preceding Induction Phase Week 16.
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Note that subjects with use of systemic immunosuppressive or immunomodulating drugs
prohibited per protocol (see Section 8.2) will be permanently discontinued from IP and will not be 
eligible for the OLE Phase (refer to Section 11.1).
For any subject in which there are no disqualifying criteria but the investigator does not believe it 
is in the best interest of the subject to continue on into the Maintenance Phase, a discussion with 
the Medical Monitor will be required prior to decision to transition to the OLE Phase.
6.4.2.12
Entry to Open-label Long-term Extension
Following completion of Week 48 of the Maintenance Phase, subjects will be eligible for entry 
into the OLE Phase based on investigator clinical judgement, that it is in the best interest of the 
subject to continue study participation. Subjects who do not qualify for entry to the OLE Phase 
will return to complete the 2 Safety Follow up Visits.
As described in Section 3.1.6. a subject may be eligible for entry to the OLE Phase at Induction 
Phase Week 16 and during the Maintenance Phase.
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 visit or the OLE-ET/EoT Visit and 2 Safety Follow-up Visits, if applicable) at the time
points outlined in the Table of Events (Table 4, Table 5, and Table 6).
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 
evaluated by considering the results of PK, 
 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 ET 
Visit and 2 Safety Follow-up Visits, if applicable) at the time points described in the Table of 
Events (Table 4, Table 5, and Table 6). 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 
 
Details of the procedures to be followed for sample collection, processing, storage, shipment, and 
testing will be documented in a separate Study Laboratory Manual. 
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Final: 20 Sep 2023
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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 Immunoglobulin G1 (IgG1)
monoclonal antibody directed against human IL-13. Investigational products (CC-93538 and 
placebo solutions for injection) are to be stored at 2°C to 8°C. The IP should not be frozen. The 
labeling will be in accordance with GCP and any other local regulatory requirements. During the 
study, IP will be dispensed in pre-filled syringes (PFS) or an 
 presentation provided by the 
Sponsor.
The 360 mg dose of CC-93538 (or placebo) will be administered by 2 injections of 1.2 mL each 
at a concentration of 150 mg/mL CC-93538 (PFS) during the Induction Phase and the Maintenance 
Phase.
During the OLE Phase, the 360 mg dose of CC-93538 will be administered by 2 injections of 1.2 
mL each at a concentration of 150 mg/mL CC-93538 (PFS) or by 1 injection of 2.0 mL at a 
concentration of 180 mg/mL CC-93538 (PFS or 
Specific handling and dispensing instructions associated with each presentation of IP are provided 
below.
Investigational Product in Pre-filled Syringes
A PFS presentation containing drug product at a concentration of 150 mg/mL CC-93538 (or 
placebo) in a 1.2 mL or at a concentration of 180 mg/mL CC-93538 in a 2.0 mL fill will be utilized 
in the study. CC-93538 solution for injection (or placebo) will be provided as a sterile liquid in 
PFS at a concentration of 150 mg/mL (or placebo) packaged in cartons (2 PFS per carton) or at a 
concentration of 180 mg/mL packaged in cartons (1 PFS per carton). CC-93538 and placebo 
solutions differ slightly in physical appearance and when presented in vials, the slight color 
difference in IP cannot be fully blinded. Therefore, for the PFS, a label cover on the active and 
placebo syringes (to be applied during packaging/labeling) will be used to maintain the blind. As 
the PFS packaging will sufficiently blind the syringe contents, an unblinded pharmacist will not 
be required to dispense IP in the PFS. At home self-administration (as outlined in Section 7.2 and 
Section 7.2.6) or administration of IP through a home health nurse (as outlined in Section 7.2 and 
Section 7.2.6) will be available IP administration options with the PFS.
Investigational Product in 
An 
 presentation containing CC-93538 drug product at a concentration of 180 mg/mL in a 2 mL 
fill (for a total of 360 mg/2 mL) will be also utilized in the OLE Phase. The CC-93538 360 mg in 
an 
 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 
 device. No additional drug 
preparation is required prior to administration. CC-93538 solution for injection will be provided 
as a sterile liquid in an 
 at a concentration of 180 mg/mL packaged in cartons (1
 per carton). 
At home self-administration (as outlined in Section 7.2.6) or administration of IP through a home 
health nurse (as outlined in Section 7.2) will be available IP administration options with the 
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Additional instructions related to IP handling, preparation, and dispensation will be provided in a
separate Study Pharmacy Manual (including an Instructions for Use document).
Note: The terms “investigational product” in this protocol will automatically be replaced with 
“post-marketing clinical study drug” on and after the date of marketing approval in Japan.
7.2
Treatment Administration and Schedule
7.2.1
Induction Phase
Subjects will be randomized 2:1 to the following treatment arms:
•
CC-93538 360 mg SC once weekly for 16 weeks 
•
Matching placebo SC once weekly for 16 weeks 
For the Induction Phase, subjects assigned to the CC-93538 360 mg SC arm will be administered
two 1.2 mL CC-93538 SC injections once weekly for 16 weeks (1.2 mL x 2 = 2.4 mL at 
150 mg/mL CC-93538 = 360 mg CC-93538/week). Subjects assigned to the placebo arm will 
receive matching placebo SC doses.
7.2.2
Maintenance Phase
Subjects who are randomized to receive CC-93538 360 mg SC once weekly in the Induction Phase
will be re-randomized 1:1 to the following treatment arms:
•
CC-93538 360 mg SC once weekly for 32 weeks
•
CC-93538 360 mg SC once every other week for 32 weeks. During the Maintenance Phase, 
matching placebo will be administered once every other week on alternate weeks to maintain 
the blind.
Subjects who are randomized to receive matching placebo in the Induction Phase will continue the 
following treatment arm:
•
Matching placebo SC once weekly for 32 weeks 
For the Maintenance Phase, subjects assigned to one of the CC-93538 360 mg arms will be 
administered two 1.2 mL CC-93538 SC injections once weekly for 32 weeks or once every other 
week for 32 weeks. Subjects assigned to the CC-93538 360 mg SC once every other week arm 
will receive a matching placebo SC dose every other week to maintain blinding. Subjects assigned 
to the placebo arm will receive matching placebo SC doses.
7.2.3
OLE Phase
•
CC-93538 360 mg SC once weekly during the OLE treatment period
For the OLE Phase, all subjects will receive CC-93538 360 mg SC once weekly during the OLE 
Phase. The dosing regimen for the OLE may be revised, via an amendment to the protocol, after 
results from the core Induction Phase and Maintenance Phase are available and the most effective 
and safest dosing regimen is confirmed.
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IP in PFS administration
On OLE Day 1, eligible subjects will be administered CC-93538 (360 mg) as two 1.2 mL CC-
93538 SC injections (150 mg/mL). Alternatively, eligible subjects may receive CC-93538 (360 
mg) as one 2 mL CC-93538 SC injection (180mg/mL).
IP in 
 administration
All subjects currently in the study and any new subjects entering the study will start receiving a 
single injection of the 360 mg/2 mL 
 once the fifth amendment to the protocol (Protocol 
Amendment 5) 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 
 presentation, a switch to 
the new 
 presentation will occur at the next regularly scheduled study visit. 
 
 
 
In the event the IP (
 is not available on-site at the time of Protocol Amendment 5 site approval, 
subjects should continue receiving the single 2.0 mL injection (180 mg/mL) using PFS 
presentation until the IP (
 is available.
7.2.4
Post Injection Observation
During the Induction Phase and the Maintenance Phase, weekly SC doses should be administered 
on the same day each week at approximately the same time of day. 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. 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.
As the OLE will include subjects previously treated with placebo, to ensure safety, and to preserve 
the maintenance of the blind from the Induction Phase and the Maintenance Phase, the first 3 
weekly SC doses will be required to be administered in the clinic for all subjects entering the OLE
Phase. 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. 
Once the new 360 mg/2.0 mL PFS presentation is introduced into the OLE Phase via the fourth 
amendment to the protocol (Protocol Amendment 4), to ensure accurate dose administration and 
compliance with 2 mL weekly SC injection using the 360 mg/2 mL PFS presentation, for subjects 
who did not begin the study with the 360 mg/2.0 mL PFS presentation at one of the first 3 weekly 
SC doses in the OLE Phase (ie, OLE Day 1, Week 1, or Week 2), one additional in-clinic weekly 
dose with at least a 30-minute observation is required for the first administration; the first dose 
with the new presentation will be administrated during an in-clinic visit.
Once the new 360 mg/2 mL 
 presentation is introduced into the OLE Phase via the fifth 
amendment to the protocol (Protocol Amendment 5), to ensure accurate dose administration and 
compliance with the new single 2 mL weekly SC injection using the 360 mg/2 mL 
 presentation, 
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Final: 20 Sep 2023
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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 
 Administration Visit as described in Table 6. 
 
7.2.5
Instructions for IP Administration
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 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).
7.2.6
Self-Administration
Self-administration (defined as either by subject or by a caregiver, applicable per local regulations) 
will be an option for dose administration of IP by the PFS/
presentation. 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 it 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 2-injection regimen no matter 
how well the subject may feel during the study. Subjects who plan to self-administer IP will be 
required to perform at least the first 3 weekly injections using the PFS presentation 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 additional 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 monthly scheduled study visits. To 
help promote consistency within the data, it is preferred that subjects do not switch their injection 
method during the 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 health nurse (where locally feasible) to 
administer the IP to the subject.
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Note: Self-administration should be performed by the subject him/herself in principle. Only if it is 
difficult for self-administration by the subject him/herself or by healthcare professionals at visits, 
self-administration by the subject’s family is allowed.
7.2.7
Missed Dose(s)
If a subject is unable to take a dose 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
See Section 7.2.9 for temporary interruption of dosing, and Section 7.2.10 for criteria for 
discontinuation of dosing.
7.2.8
Dose Adjustments
There is no provision for dose adjustments in this study. Subjects who cannot tolerate their 
assigned dose of IP, as determined by the investigator, will be permanently discontinued from IP 
(see Section 11.1).
7.2.9
Guidelines for Temporary Interruption of Dosing
Dosing should be interrupted (temporary discontinuation of IP) if any of the following events 
occur:
•
Severe laboratory abnormalities in which a causal relationship to IP is not suspected of being 
related (ie, a causal relationship is unlikely or remote, or another medication, therapeutic 
intervention or underlying condition provides a sufficient explanation)
•
An infection requiring parenteral treatment with antibiotic, antifungal, antiviral, antiparasitic, 
or antiprotozoal medications; for an infection requiring oral treatment with these medications 
for longer than 2 weeks, the investigator should determine if an interruption of dosing is in the 
best interest of the subject
•
Any AE, intercurrent medical condition, or major surgery that could present an unreasonable 
risk to the subject due to continued study participation, as determined by the investigator
•
For subjects who develop suspected or confirmed symptomatic COVID-19 infection, or it is 
discovered that subjects have asymptomatic COVID-19 infection during the Treatment Period
(Induction Phase, the Maintenance Phase, and the OLE Phase). Investigational product should 
be temporary interrupted until the following conditions are met: 
−
For symptomatic subjects:
♦At least 10 days (20 days for severe/critical illness) have passed since symptoms first 
appeared or positive test result, and
♦At least 24 hours have passed since last fever without the use of fever-reducing 
medications, and
♦Symptoms (eg, cough and shortness of breath) have resolved and
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♦In the opinion of the investigator, there are no COVID-19 sequelae that may place the 
subject at a higher risk of receiving investigational treatment, and,
♦Negative follow-up molecular test for COVID-19 based on most current institutional, 
local, or regional COVID-19 guidelines and/or requirements.
−
For asymptomatic subjects:
♦At least 7 days have passed since positive test result (based on date of collection, not 
date of test result availability), and,
♦Negative follow-up molecular test for COVID-19 based on most current institutional, 
local, or regional COVID-19 guidelines and/or requirements.
The decision to interrupt dosing of IP remains the responsibility of the treating physician, which
will not be delayed or refused by the Sponsor. However, prior to interruption of dosing, the 
investigator may contact the Medical Monitor and forward appropriate supporting documents for
review and discussion. Once the laboratory abnormality stabilizes (and is not suspected of being
related to IP) or the condition resolves, IP dosing may be resumed at the discretion of the 
investigator in consultation with the Medical Monitor if 3 or more consecutive doses have not been 
missed (3 or more consecutive missed doses requires permanent discontinuation of IP). If dosing 
is interrupted for any reason (AE, non-compliance, etc), the investigator should contact the 
Medical Monitor to discuss when/if IP dosing should be resumed.
7.2.10
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 IP. These subjects will 
be encouraged to remain in the study and complete all required study assessments in the phase of 
the study that permanent discontinuation of IP occurs with the exception of IP dosing, and will not 
be allowed to participate in the OLE Phase, if the subject participates in the Induction Phase and 
the Maintenance Phase. In order to prevent missing data, the site staff will ensure attempts are 
made to reach subjects by telephone or email that do not maintain contact with the investigator. 
Any subject discontinuing the study prematurely will be asked to complete the ET visit or the 
OLE-ET/EoT Visit and the Interim and the Final Safety Follow-up Visits.
7.2.11
Rescue Therapy
Subjects with a worsening of EGE symptoms requiring rescue therapy (defined as a severe EGE 
flare; refer to Section 6.4.2.10) during the Induction Phase may continue to participate in the phase 
of the study in which the EGE flare occurs. If the results of the gastric/duodenal eos count were
required to determine rescue therapy during the Induction Phase, the subject will be withdrawn 
from the study. Subjects with a worsening of EGE symptoms requiring rescue therapy during the 
Maintenance Phase may enter the OLE Phase. Rescue therapy includes EGE standard of care 
pharmacotherapy (eg, including but not limited to concomitant corticosteroid therapy over the 
baseline dose) and/or dietary modification (eg, food elimination diet).
Concomitant use of systemic corticosteroid therapy with or under the baseline dose of concomitant 
corticosteroid treatment is not considered as rescue therapy. 
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7.3
Method of Treatment Assignment
7.3.1
The Induction Phase and the Maintenance Phase
Subjects enrolled in the Induction Phase will be centrally randomized on Day 1 after all screening 
and baseline assessments have been completed and the investigator has verified that the subject is 
eligible per the inclusion (Section 4.2) and exclusion criteria (Section 4.3). Subjects will be 
randomized 2:1 to receive active CC-93538 treatment (360 mg SC weekly for 16 weeks) or 
matching placebo for 16 weeks. Treatment assignment at baseline will be stratified by 
(with/without) concomitant use of corticosteroid treatment at baseline (up to 10 mg/day as the 
equivalent of prednisone) to ensure an equal balance in the treatment arms. Randomization will be 
performed through the Interactive Web Response System (IWRS) system.
Subjects enrolled in the Maintenance Phase will be centrally re-randomized on Week 16 (the 
completion of Induction Phase). Subjects who randomized to receive CC-93538 360 mg SC once 
weekly in the Induction Phase will be re-randomized 1:1 to receive active CC-93538 treatment 
(360 mg SC once weekly or 360 mg SC once every other week), and subjects who randomized to 
receive matching placebo in the Induction Phase will continue placebo. Re-randomization will also 
be performed through the IWRS system.
Treatment groups are described in Section 7.2. The treatment each subject will receive will not be 
disclosed to the investigator, study center personnel, subject, Sponsor, or their representatives. The 
treatment codes will be held according to the IWRS. Further instructions will be provided in a 
separate IWRS manual.
The study blind should be maintained for persons responsible for the ongoing conduct of the study 
(after all subjects have completed the Week 48 assessments for endpoint analysis). Blinded persons 
may include but are not limited to: Clinical Research Physician (also referred to as Clinical Trial 
Physician), Clinical Research Scientist, Clinical Trial Manager, Study Statistician, Data Manager, 
Programmers, and Clinical Research Associates. For details of the emergency procedure for 
unblinding of individual subjects, see Section 11.4.
7.3.2
The OLE Phase
After all OLE baseline assessments have been completed, 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 Phase.
7.4
Packaging and Labeling
7.4.1
The Induction Phase and the Maintenance Phase
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. For the PFS 
presentation, a label cover on the active and placebo syringes will be used to maintain the blind.
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7.4.2
The OLE Phase
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 and placebo 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 
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 contract 
research organization 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
There are specific requirements for cessation of medication use prior to enrollment, as stated in 
the exclusion criteria (Section 4.3). All treatments (including prescription and over the counter  
medications, herbal and dietary supplements, dietary modifications, vaccines, and procedures) 
used by subjects within the 4 weeks (28 days) prior to the first Screening Visit or 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. In addition, a history of previous treatments 
for EGE will be documented. The investigator must document all treatments received at the time 
of the EGD (for any indication) through Day 1.
All concomitant treatments, including blood and blood products, used from 28 days prior to the 
first Screening Visit until 16 weeks after the last dose of IP or until the Final Safety Follow-up 
Visit, whichever is longer, must be reported on the eCRF.
8.1
Permitted Concomitant Medications and Procedures
Concomitant medications, dietary modifications, and procedures that are permitted during the 
study include the following:
•
Subjects must have maintained a stable diet for at least 4 weeks prior to the first Screening
Visit and must agree to maintain a stable diet throughout the Induction Phase and the
Maintenance Phase. Subjects on a food elimination diet for the treatment of food allergy or
EGE should maintain it without making any changes through the end of the study and should
have maintained this diet for at least 4 weeks prior to the first Screening Visit. Subjects must
agree to not introduce any changes in their diet while participating in the Induction Phase and
the Maintenance Phase. However, following IP administration, subjects experiencing a severe
EGE flare requiring a dietary modification for rescue therapy may be eligible to continue in
the study according to protocol requirements. See Section 6.4.2.10.
•
Subjects may use systemic corticosteroids up to 10 mg/day of prednisone for EGE as a
concomitant corticosteroid treatment. Stable doses/regimens must have been maintained for at
least 4 weeks prior to the first Screening Visit and regimens will remain stable until Week 16
(completion of the Induction Phase). If the reduction of EGE-related symptoms is observed
after Week 16 (in the Maintenance Phase and the OLE Phase), the investigator should begin
tapering dosage regimen of concomitant corticosteroid treatment after Week 16. The dose
reduction should be 2.5 mg/week (as the equivalent of prednisone).
•
Subjects may use inhaled corticosteroids, proton pump inhibitors (PPIs), leukotriene receptor
antagonists (eg, montelukast), or mast cell stabilizers (eg, cromolyn sodium) for indications
other than EGE if on stable doses/regimens for at least 4 weeks prior to the first Screening
Visit and regimens will remain stable throughout the Induction Phase and the Maintenance
Phase. If one of these medications was recently discontinued, it must have been discontinued
at least 4 weeks prior to the first Screening Visit.
•
Subjects may use medium potency topical corticosteroids (eg, mometasone furoate cream or
lotion) for dermatologic conditions if on stable doses/regimens for at least 4 weeks prior to the
first Screening Visit and regimens will remain stable throughout the Induction Phase and the
Maintenance Phase. If the medication was recently discontinued, it must have been
discontinued at least 4 weeks prior to the first Screening Visit.
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•
Subjects may use intranasal corticosteroids, antihistamines, or other medications for seasonal
allergies or other conditions as needed.
•
Subjects may use low potency topical corticosteroids for dermatological conditions as needed.
•
Subjects receiving PPIs, leukotriene receptor antagonists (eg, montelukast), or mast cell
stabilizers (eg, cromolyn sodium) medication for the indication of EGE at the first Screening
Visit may participate if these medications has been maintained at a stable dose from at least 4
weeks prior to the first Screening Visit through the Induction Phase and the Maintenance
Phase. Subjects who discontinued these medications must not have received these medications
for at least 4 weeks before the First Screening Visit and must agree not to restart these
medications during the study. However, following IP administration, subjects experiencing a
severe EGE flare requiring the addition of these medications or modification to these
medication regimens for rescue therapy may be eligible to continue in the study according to
protocol requirements. See Section 6.4.2.10.
•
Subjects receiving SC immunotherapy must have been on stable doses for at least 3 months
prior to the first Screening Visit and for the Induction Phase and the Maintenance Phase.
•
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 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.
Refer to Table 7 for a summary of the timing for stable dosing regimen requirements for certain 
medications and requirement for a stable diet.
8.1.1
Rescue Therapy
During the study, subjects with a worsening of EGE symptoms requiring rescue therapy (defined 
as a severe EGE flare; refer to Section 6.4.2.10) may be eligible to continue to participate in the 
study according to protocol requirements. Rescue therapy includes EGE standard of care 
pharmacotherapy (including but not limited to systemic corticosteroid therapy over the baseline 
dose) and/or dietary modification (eg, food elimination diet). Note that as part of study eligibility 
criteria and as described below in Section 8.2, in general, use of these treatment modalities is 
prohibited unless documented as required therapy for an EGE flare following IP administration.
Concomitant used of systemic corticosteroid therapy with or under the baseline dose (up to 
10 mg/day of prednisone) is not considered as rescue therapy.
8.2
Prohibited Concomitant Medications and Procedures
Concomitant medications and procedures that are prohibited for a specific time period prior to the 
first Screening Visit and throughout the duration of the study include the following (the timeframe 
before the first Screening Visit is specified below); however, exceptions will occur in the event of 
a severe EGE flare requiring rescue therapy and in such cases, subjects may continue participation 
with concomitant rescue therapy (eg, systemic corticosteroids over 10 mg/day as prednisone). In 
such cases, a subject may be eligible to participate in the OLE Phase (Section 3.1.6):
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•
Subjects may not use systemic immunosuppressive or immunomodulating drugs (including
but not limited to, 
 α4β7 integrin inhibitor antibodies, or
any other monoclonal antibodies, methotrexate, cyclosporine, azathioprine, mercaptopurine,
IFNα, TNFα inhibitors, etc) for at least 5 drug half-lives prior to the first Screening Visit and
during the study (including the OLE Phase). Use of any of the aforementioned medications
during study participation will result in the subject’s permanent discontinuation from IP;
exceptions are if corticosteroids are used as rescue therapy for an EGE flare (see Section 8.1.1)
or if required for treatment of an AE upon discussion with the Medical Monitor.
•
Subjects may not use systemic corticosteroid medication exceeding the baseline dose as
background treatment (up to 10 mg/day of prednisone) from the first Screening Visit through
the Induction Phase and the Maintenance Phase. Subjects who have received corticosteroid
therapy for EGE or another indication must have decreased the dose under 10 mg/day of
prednisone and kept the systemic corticosteroid dose at that level within 4 weeks of the first
Screening Visit. However, if a subject experiences a severe EGE flare during study
participation following IP administration, the subject may continue participating in the
Induction Phase and the Maintenance Phase with concomitant corticosteroid rescue therapy
according to protocol pre-specified criteria (see Section 6.4.2.10).
•
Subjects may not use high potency topical corticosteroids (eg, augmented betamethasone
dipropionate, clobetasol propionate, etc) for dermatologic conditions within 8 weeks prior to
the first Screening Visit through the Induction Phase and the Maintenance Phase.
•
If subjects have not received PPIs, leukotriene receptor antagonists (eg, montelukast) or mast
cell stabilizers (eg, cromolyn sodium) for the indication of EGE prior to the first Screening
Visit, the subjects may not initiate these medications for the indication of EGE after 4 weeks
prior to the first Screening Visit through the Induction Phase and the Maintenance Phase.
•
Subjects may not receive oral or sublingual immunotherapy (treatment to desensitize to an
allergen) within 6 months prior to the first Screening Visit through the end of the study
(including the OLE Phase).
•
Subjects may not receive live (including attenuated) vaccines within 1 month prior to the first
Screening Visit through the end of the study (including the OLE Phase).
•
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 and
through the end of the OLE study. For subjects who received an investigational COVID-19
vaccine as part of a clinical trial prior to the first Screening Visit, enrollment must be delayed
until the biologic impact of the vaccine is stabilized, as determined by discussion between the
investigator and the Clinical Trial Physician.
Refer to Table 7 for a summary of the timing of restrictions on medication use as well as for certain 
procedures or dietary modifications required prior to study enrollment.
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Table 7:
Medications, Diets, or Procedures Requiring Stable Dosing Regimens or Restricted Use Prior to Study 
Enrollment
Medication, Diet or Procedure
Restriction Timeframe
Medication (or procedure)
Subjects must not have received the 
following medication within the 
timeframe below before the first 
Screening Visit
Induction/Maintenance 
Phase
Open-label 
Long-term
Extension
(OLE) Phase 
Systemic immunosuppressive or immunomodulating drugs
5 half-lives
Prohibited
Prohibited
Systemic corticosteroids exceeding the baseline dose (up to 
10 mg/day of prednisone)
4 weeks
Prohibited
No restriction
High potency topical corticosteroids
8 weeks
Prohibited
No restriction
Initiation of proton pump inhibitors (PPIs), leukotriene receptor 
antagonists or mast cell stabilizers (for the indication of 
eosinophilic gastroenteritis [EGE])
4 weeks
Prohibited
No restriction
Oral or sublingual immunotherapy
6 months
Prohibited
Prohibited
Live (including attenuated) vaccines
1 month
Prohibited
Prohibited
Any other investigational product a
5 half-lives
Prohibited
Prohibited
Medication (or diet)
Subjects must be on stable dosing 
regimens within the timeframe below 
before the first Screening Visit
Induction/Maintenance 
Phase
OLE Phase 
Diet (eg, food elimination diet)
4 weeks
Stable
No restriction
Systemic corticosteroid therapy with or under the baseline dose 
(up to 10 mg/day of prednisone)
4 weeks
Stable/Induction Phase
Can be tapered or increased 
to the baseline dose
/Maintenance Phase 
No restriction, 
tapering is 
recommended
Inhaled corticosteroids, proton pump inhibitors (PPIs), 
leukotriene receptor antagonists, or mast cell stabilizers (for 
indications other than EGE)
4 weeks
Stable
No restriction 
PPIs, leukotriene receptor antagonists, or mast cell stabilizers 
(for indications of EGE)
4 weeks
Stable
No restriction
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Table 7:
Medications, Diets, or Procedures Requiring Stable Dosing Regimens or Restricted Use Prior to Study 
Enrollment
Medication, Diet or Procedure
Restriction Timeframe
Medication (or procedure)
Subjects must not have received the 
following medication within the 
timeframe below before the first 
Screening Visit
Induction/Maintenance 
Phase
Open-label 
Long-term
Extension
(OLE) Phase 
Medium potency topical corticosteroids for dermatologic 
conditions
4 weeks
Stable
No restriction 
Subcutaneous immunotherapy
3 months
Stable
No restriction 
a For subjects who received an investigational Coronavirus disease 2019 (COVID-19) vaccine as part of a clinical trial prior to the first Screening Visit, enrollment 
must be delayed until the biologic impact of the vaccine is stabilized, as determined by discussion between the investigator and the Clinical Trial Physician.
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8.3
Required Concomitant Medications and Procedures
See inclusion criteria and exclusion criteria (Section 4.2 and Section 4.3) for a description of
corticosteroid treatment requirements and PPIs, leukotriene receptor antagonists, or mast cell 
stabilizer medication requirements and for study eligibility. See Section 6.1 for Screening EGD 
requirements.
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9
STATISTICAL CONSIDERATIONS
9.1
Overview
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled induction and 
maintenance study to assess the efficacy and safety of CC-93538 in adult and adolescent subjects 
with EGE. The study will incorporate a 16-week Induction Phase followed by a 32-week 
Maintenance Phase and an OLE Phase. Subjects will be randomized according to the following 
stratification factor: concomitant steroid use (yes or no). An independent DMC will be used to 
review the safety data regularly during the course of the study.
A primary database lock will be performed when all randomized subjects in this study have 
completed Week 48 of the Maintenance Phase or discontinued the study, including all Safety 
Follow-up Period data available to date. Analyses in the primary clinical study report (CSR) will 
be based on this database.    
Analysis details not explained in the statistical section of the protocol will be provided in the 
Statistical Analysis Plan (SAP).
9.2
Study Population Definitions
All study populations will be defined and documented prior to database lock. The following 
analysis populations will be used in the statistical analysis:
Intent-to-treat (ITT) Population
The ITT population will consist of all randomized subjects regardless of whether or not the subject 
received IP (CC-93538 or placebo).
The ITT population will be used as the primary population for all efficacy parameters. Subjects 
who prematurely withdraw from the trial for any reason and for whom an assessment is not 
performed for any reason will still be included in the ITT analyses. Subjects who received incorrect 
IP from what was randomized will be included in the treatment group according to the intended 
randomization. Subjects who were randomized with a misreported stratum will be analyzed 
according to their original (misreported) stratum.
Safety Population
The Safety population will consist of all subjects who received at least one dose of IP. This 
population will be used for all summaries of safety data. Subjects randomized to placebo who
receive any dose of CC-93538 will be summarized in the CC-93538 group. Subjects randomized 
to CC-93538 who receive only placebo will be summarized in the placebo group; otherwise, they 
will be summarized in the CC-93538 group.
9.3
Sample Size and Power Considerations
The sample size is based on two-sample t-test for the primary endpoint, changes in mean number 
of peak eos per hpf in GI biopsies from baseline to Week 16. The null hypothesis and the 
alternative hypothesis for the primary endpoint are as follows;
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•
Changes in mean number of peak eos from baseline at Week 16
Null hypothesis H0: μCC-93538 = μPlacebo
Alternative hypothesis Ha: μCC-93538 ≠ μPlacebo,
where μCC-93538 represents the true mean change value relative to CC-93538 and μPlacebo represents
true mean change value relative to placebo.
Using this hypothesis, if the expected mean change in eos count in the active treatment group was 
-70, the expected mean change in eos count in the placebo group was 0, and the standard deviation
(SD) was 70, the sample size necessary to achieve at least 80% power in a t-test at a significance
level of 0.05 was calculated. Using a 2:1 ratio of active to placebo, 39 subjects are required.
Assuming a Week 16 drop-out rate of approximately 10%, the goal is to enroll a total of 45
subjects.
The expected change from baseline in eos count in the active treatment group is based on the Phase 
2 EoE study (Study RPC02-201); mean value at baseline for the CC-93538 360 mg treatment 
group of 139.4, and mean value at Week 16 of 31.3, with a percent change of approximately 80%. 
The baseline value in patients with EGE was assumed to be approximately 90 based on the results 
of studies of other drugs in patients with EGE (Dellon, 2020). Therefore, the expected change from 
baseline in eos in the active treatment group is assumed to be approximately 70. Change from 
baseline in eos count in the placebo group was assumed to be 0 based on the results of studies of 
other drugs (Dellon, 2020). With reference to the baseline GI eos count results of other drug studies 
of 52 (Dellon, 2020), the results of Study RPC02-201 in the CC-93538 360 mg group of 90, and 
the results of Study RPC02-201 in the CC-93538 180 mg group of 71, SD was assumed to be 70, 
which is approximately the mean of those values.
9.4
Background and Demographic Characteristics
Summaries for the demographics, baseline characteristics, medical history, prior medication, and 
protocol deviations will be presented for the ITT population by treatment for the Induction Phase 
and by treatment and in total CC-93538 for the Maintenance Phase. Concomitant medications will 
be presented for the Safety population by treatment for the Induction Phase, and by treatment and 
in total CC-93538 for the Maintenance Phase. Individual listings will also be provided, including 
concomitant medical procedures for the Safety population.
9.5
Subject Disposition
The disposition of subjects will be summarized with numbers and percentages by treatment for all 
randomized subjects. Summaries will include the number and percentage of subjects in the 
following categories:
•
Never dosed, dosed, completed the study, permanently discontinued from IP, and
discontinuation from the study
•
Time to permanent discontinuation from IP and time to discontinuation from the study
•
Primary reasons for discontinuation from the study
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Subjects in each analysis population as defined in Section 9.2 will be summarized with number 
and percentage.
9.6
Efficacy Analysis
9.6.1
Efficacy Analysis of the Primary Endpoint
9.6.1.1
Intercurrent Event and Analysis Strategies
The following are the intercurrent events (ICEs) of interest: 
1. Treatment discontinuation in subjects without the use of concomitant rescue therapy or
prohibited medication (subjects remain in the study)
2. The use of concomitant rescue therapy or prohibited medication which may impact the
efficacy assessment for CC-93538
3. Treatment discontinuation followed by rescue therapy or prohibited medication which may
impact the efficacy assessment for CC-93538
For intercurrent event (ICE) number 1, all observed data will be included in the primary analysis 
regardless of the occurrence of the ICE according to the respective endpoint definition. For ICE
numbers 2 and 3, all observed data will be included in the primary analysis. 
9.6.1.2
Changes in Mean Number of Peak eos Count from Baseline to Week 16 
(Induction Phase)
The primary analysis will be conducted on the ITT population based on an analysis of covariance 
(ANCOVA) model with treatment group, concomitant steroid use (yes or no), and baseline eos 
count included in the model. The comparison between CC-93538 360 mg SC once weekly and 
placebo for change in number of peak eos count from baseline at Week 16 will be made using the 
difference in least squares mean (LSM) at a 5% 2-sided significance level. Point estimates for the 
mean difference between the two treatment groups using the LS mean changes and corresponding 
95% Wald CI will be reported. In addition, LSMs (standard error [SE]), arithmetic means (SD), 
and arithmetic mean changes (SD) will be summarized by treatment group. 
Missing data will be handled using a multiple imputation (MI) approach under a missing at random 
(MAR) assumption.
Sensitivity analyses will be performed to support the primary analysis and provide additional 
insights to understand the treatment effect. For the primary estimand analysis, robustness due to 
missing data MI under MAR assumption will be explored using tipping point analysis (Yan, 2009; 
Campbell, 2011; Yuan, 2014). In considering the ICEs of study interest (ie, ICE number 2, use of 
rescue therapy/prohibited medication, and ICE number 3, treatment discontinuation followed by 
use of rescue therapy/prohibited medication), an analysis using the hypothetical estimand strategy 
for change in eos count at Week 16 will be conducted.
9.6.2
Subgroup Analyses
To assess whether the treatment effect is consistent across various groups, subgroup analyses will 
be performed for the primary endpoint at Week 16. Treatment differences and 2-sided 95% CIs 
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will be provided for each subgroup listed below. Forest plots for the treatment differences by 
subgroup will also be provided.
1. Concomitant steroid use (yes versus no)
2. Prior history of corticosteroid use for the treatment of EGE (yes versus no)
3. Age group (adolescents [12 to 17 years] versus adults [≥ 18 years], non-elderly adults
[< 65 years] versus elderly adults [ ≥ 65 years]).
For EGID Severity Score, adolescents is set as 12 to 19 years
4. Sex (female versus male)
If there are not enough subjects within a subgroup enabling a valid statistical inference, the 
corresponding subgroup analyses will not be performed, and summary statistics will be provided
instead.
9.6.3
Analysis of Secondary Efficacy Endpoints
9.6.3.1
Analyses Methods
Continuous variables:
•
Changes in mean number of peak eos count per hpf from baseline to Week 48
•
Changes from baseline in each of 5 domain scores of the Izumo Scale (Weeks 14, 16, 32, and
48)
•
Changes from baseline in total score of EGID Severity Score (Weeks 16, 32, and 48)
•
Percent changes in mean number of peak eos per hpf in GI biopsies from baseline (Weeks 16
and 48)
•
The time until concomitant corticosteroid treatment to zero (and continued by Week 48) (from
Week 16 through Week 48)
The analysis for continuous variables of the secondary endpoints will be conducted on the ITT 
population using the ANCOVA model with treatment group (CC-93538 360 mg SC once weekly, 
CC-93538 360 mg SC once every other week, and placebo), prior steroid use (yes or no), and
baseline values included in the model. Point estimates for the mean difference between the
treatment groups using the LS mean changes and corresponding 95% Wald CI will be reported.
The transition from the Maintenance Phase to the OLE Phase will be treated as ICE. Missing data
and ICEs will be handled via the same strategy as for the primary analysis.
Dichotomous variables:
•
The proportion of responders defined as subjects who achieve both clinical and histologic
response (Weeks 16 and 48):
−
Clinical response is defined as the proportion of subjects achieve < 4/15 in all Symptoms
of Interest (Gastric Pain Symptoms domain, Stomach Heaviness Symptoms domain, and
Diarrhea Symptoms domain) of the Izumo Scale
−
Histologic response is defined as a > 75% reduction of peak gastric and/or duodenal eos
count from baseline
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•
The proportion of subjects achieving eosinophilic histologic response defined as a > 75%
reduction of peak gastric and/or duodenal eos count from baseline (Weeks 16 and 48)
•
The proportion of subjects who achieve < 4/15 in all Symptoms of Interest (Gastric Pain
Symptoms domain, Stomach Heaviness Symptoms domain, and Diarrhea Symptoms domain)
of the Izumo Scale (Weeks 14 to 16, 30 to 32, and 46 to 48)
•
The proportion of subjects for whom the dose of concomitant steroids is reduced to zero
(Weeks 24, 32, 40, and 48)
The analysis of the response endpoint will be conducted on the ITT population using the Cochran-
Mantel-Haenszel (CMH) test stratified by concomitant corticosteroid treatment at baseline (yes or 
no). In case the Mantel-Fleiss criterion is not met, the Fisher’s exact test will be performed instead 
of the CMH test. For treatment comparison between a CC-93538 dose and placebo, the 2-sided 
95% stratified Newcombe CI (Yan, 2010) for the difference in proportions using the CMH weights 
will be provided. Missing data and any observed data after rescue therapy/prohibited medication 
which may impact the efficacy assessment will be set as non-responders.
Time to event data:
•
The time to event of EGE flare (Through Week 48)
•
The time to event of use of rescue therapy (Through Week 48)
•
The time until concomitant corticosteroid use to zero (From Week 16 through Week 48)
For the time-to-event endpoints, the numbers of subjects who have an event will be summarized. 
The Kaplan-Meier (KM) estimates of the 25th, median, and 75th percentile of the time to the first 
event and the 2-sided 95% CIs will be provided. The cumulative number of events, the number of 
subjects at risk, and the KM estimate of the event rate (i.e., failure probability instead of survival 
probability) and SE will be provided by time point. The KM plot of failure curves (instead of 
survival curves) with the number of subjects at risk at each time point will be presented. To test 
the KM curve in the treatment group is different from that in the placebo group in at least one 
stratum, a stratified log-rank test will be conducted.
Multiplicity Adjustment
Only one formal statistical test will be performed for the primary endpoint. For any other 
comparisons, nominal p-value (without adjustment for multiplicity) will be provided as a measure 
of the strength of association between the endpoint and the treatment effect rather than a formal 
statistical test. Therefore, the multiplicity adjustment is not applicable in this study.
9.7
Safety Analysis
Safety analysis will be performed for the Induction Phase and by treatment and in total CC-93538 
for the Maintenance Phase. The assessment of safety 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. Safety data 
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will be summarized by treatment group using descriptive statistics. Individual data listings will 
also be provided.
Adverse events will be monitored during the study, and the data will be analyzed with respect to 
incidence within each treatment group as well as severity and potential relationship of the AEs to 
IP.
Laboratory assessments will be performed by a central laboratory. All summaries will be based on 
the standard International System of Units (SI) provided by the central laboratory. Each subject’s 
hematology, blood chemistry, and urinalysis values will be flagged as “low”, “normal”, or “high” 
relative to the normal ranges of the central laboratory.
Summary statistics of actual values and changes from baseline in vital signs will be provided by 
visit.
Overall safety and tolerability will be summarized for each drug presentation (the 360 mg dose of 
CC-93538 administered by two injections of 1.2 mL each at a concentration of 150 mg/mL CC-
93538 or by one injection of 2.0 mL at a concentration of 180 mg/mL CC-93538 administered
with the PFS device constituent part or by one injection of 2 mL at a concentration of 180 mg/mL
CC-93538 administered with the 
 device constituent part) utilizing descriptive statistics.
9.8
Interim Analysis
No formal interim analysis will be conducted for the study.
9.9
Other Topics
9.9.1
Pharmacokinetics, 
Serum trough concentrations (Ctrough) of CC-93538 will be summarized with descriptive statistics 
by treatment and visit. Additional analyses may be conducted as appropriate (eg, by ADA status).
 
 
 
 
 
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9.9.3
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 
laboratory findings will be reviewed internally by the Celgene 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).
9.9.4
External Data Monitoring Committee
Safety monitoring will also be performed by an external, independent DMC. A DMC will be 
convened that will be comprised of physician experts with experience in treating subjects with 
EGE 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 a blinding plan 
to assure that all personnel involved in the conduct of the study remain blinded to the results of 
data reviews, will also be described in the DMC charter.
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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 EGE flare 
requiring an EGE Flare Assessment, as referenced in Section 6.4.2.10. However, any EGE flare 
that meets the criteria for seriousness as detailed in Section 10.2.1, should be documented as an 
SAE in addition to an EGE flare. A diagnosis or syndrome should be recorded on the AE page of 
the case report form (CRF) rather than the individual signs or symptoms of the diagnosis or 
syndrome. 
Abuse, withdrawal, sensitivity or toxicity to an IP should be reported as an AE. Overdose, 
accidental or intentional, whether or not it is associated with an AE should be reported on the 
overdose CRF. (See Section 7.2 for the definition of overdose.) Any sequela of an accidental or 
intentional overdose of an IP which meets the definition of an adverse event, should be reported 
as an AE on the CRF. If the sequela of an overdose meets serious criteria, then it must be marked 
as serious on the CRF. The overdose itself should not be reported as an AE.
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for CC-93538 overdose. 
Actual treatment should depend on the severity of the clinical situation and the judgment and 
experience of the treating physician.
All subjects will be monitored for AEs, 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, 
/PFS device  
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 specialized eCRF pages, 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 until 16 weeks after the last dose of IP or
the final 16-week Safety Follow-up Visit, whichever is longer, as well as those SAEs made known 
to the investigator at any time thereafter that are suspected of being related to IP. AEs and SAEs
will be recorded on the AE page of the eCRF and in the subject’s source documents. Refer to 
Section 10.5 for instructions on how to report SAE to Drug Safety.
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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. 
•
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”.
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For each AE, the investigator will provide information on severity, start and stop dates, relationship 
to the IP, action taken regarding the IP, and outcome.
10.2.2
Severity/Intensity
For 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 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 each 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. 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:
•
results in discontinuation from the study;
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•
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 by facsimile, or other appropriate method,
within 24 hours of the investigator’s knowledge of the event using the SAE Report Form, or 
approved equivalent form.
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 
related to the in utero exposure to the IP should also be reported to Celgene Drug Safety by 
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facsimile, or other appropriate method, within 24 hours of the investigator’s knowledge of the 
event using the SAE Report Form, or approved equivalent form.
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 EDC. All SAEs must be reported to Celgene Drug 
Safety via EDC within 24 hours of the investigator’s knowledge of the event. This instruction 
pertains to initial SAE reports as well as any follow-up reports.
The investigator is required to ensure that the data on these forms is accurate and consistent. This 
requirement applies to all SAEs (regardless of relationship to IP) that occur during the study (from 
the time the subject signs informed consent until 16 weeks after the last dose of IP or through the 
Final 16-week Safety Follow-up Visit, whichever is longer) or any SAEs made known to the 
investigator at any time thereafter that are suspected of being related to IP. Serious adverse events 
occurring prior to treatment (after signing the ICF/assent) are to be recorded within the eCRF and 
reported to Celgene Drug Safety.
The SAE report entered into EDC 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 via EDC as soon as these become available. Any follow-up data should be 
added to the existing SAE case in EDC.
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.
The SAE is recorded within the eCRF, and the data is transmitted electronically to Celgene Drug
Safety. In the event electronic transmission is not available, a paper SAE Report Form will be
completed and sent directly to Celgene Drug Safety, ensuring the event is recorded on the eCRF
as well.
10.5.1
Safety Queries
Queries pertaining to SAEs will be communicated through EDC.
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 
. These include:
•
Anaphylactic reactions
•
Systemic or severe hypersensitivity reactions
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•
Severe injection site reactions (ISRs) that last longer than 24 hours
−
A severe ISR is defined as an ISR that manifests with symptoms causing severe 
discomfort/pain; symptoms requiring medical/surgical attention/intervention; interference 
with ADLs including inability to perform daily social and functional activities (eg, 
absenteeism and/or bed rest); and/or when drug therapy is required.
•
Malignancies except in situ carcinoma of the cervix or non-metastatic squamous cell or basal 
cell carcinoma of the skin
•
Helminthic or parasitic infections
•
Opportunistic infections
•
Any severe infections; or infections requiring treatment with parenteral antibiotic, antiviral, or 
antifungal medications; or infections requiring treatment with oral antibiotic, antiviral, or 
antifungal medications for longer than 2 weeks
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.
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 Celgene and 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 discontinuing a subject from the IP(s):
•
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 IP:
•
Pregnancy
•
An SAE which is suspected of being related to IP
•
Anaphylactic reaction or other severe systemic reaction (eg, hypersensitivity, allergic, or 
autoimmune) suspected of being related to IP
•
Malignancy diagnosis, excluding carcinoma in situ of the cervix or squamous or basal cell 
carcinoma of the skin if it can be successfully treated by local resection
•
Presence of an opportunistic infection suggestive of immunocompromisation
•
The following severe laboratory abnormalities suspected of being related to IP (laboratory 
indices should be repeated for confirmation prior to permanent IP discontinuation, within 
48 to 72 hours after the abnormality was first observed):
Ѹ
Neutrophil count ≤ 0.5 × 103/μL
Ѹ
Platelet count ≤ 50 × 103/μL
Ѹ
ALT and/or AST values > 3 × ULN with total bilirubin > 2 × ULN or INR > 1.5, 
excluding confirmed Gilbert Syndrome or therapeutic anticoagulation
Ѹ
ALT and/or AST > 5 × ULN for greater than 2 weeks duration
•
3 or more consecutive missed doses, unless in consultation with the Medical Monitor it is 
determined that despite 3 or more consecutive missed doses it is in the best interest of the 
subject to continue participation with the possibility of re-starting CC-93538 at an 
appropriate time in the future
•
Disclosure of the results of the gastric/duodenal eos count (in Induction Phase only)
•
Use of systemic immunosuppressive or immunomodulating drugs prohibited per protocol
(see Section 8.2)
Note: INR is part of the coagulation panel and may be obtained at the discretion of the investigator 
via central or local laboratory testing. 
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Subjects who are permanently discontinued from IP will be encouraged to continue participation 
in the study without IP administration in order to complete all remaining required study 
assessments, including efficacy evaluation, in the phase of the study that permanent 
discontinuation from IP occurs. If discontinuation from IP occurs during the Induction Phase, 
subjects will not be eligible to continue into the Maintenance Phase and will be discontinued from 
the study. Subjects who are permanently discontinued from IP will not be eligible to enter the OLE 
Phase. Subjects who continue study participation in the phase that the discontinuation occurs will 
return for the Interim and Final Safety Follow-up Visits 8 and 16 weeks after their last study visit.
In the OLE Phase, 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, 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
Note that subjects who are permanently discontinued from IP (as detailed in Section 11.1) but are 
not discontinued from the study will be encouraged to continue participation in order to complete 
all remaining required study assessments in the phase of the study that permanent discontinuation 
from IP occurs. 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. 
In the OLE Phase, Subjects who demonstrate a persistent lack of improvement or worsening of 
EGE symptoms should be evaluated to determine if continuing the study treatment is appropriate. 
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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.
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.
In the Induction Phase, subjects who discontinue from the study for any reason prior to completing 
Week 16, or who complete Week 16 and do not enter the Maintenance Phase will complete an ET 
Visit conducted as close as possible to the time of study discontinuation. If study discontinuation 
occurs at the regularly scheduled visit (eg, Induction Phase Week 16) the ET Visit/procedures 
should be performed. These subjects, with the exception of those continuing in the OLE Phase, 
will also have 2 Safety Follow-up Visits (at 8 and 16 weeks) after final IP administration for the 
assessment of safety and clinical status after exiting the study. For subjects who are permanently 
discontinued from IP during the Induction Phase and remain in the study to complete safety and 
efficacy assessments, the Interim and Final Safety Follow-up Visits will be conducted at 8 and 16 
weeks, respectively, after their last study visit in the Induction Phase. Assessments should be 
performed in accordance to the schedule of events (Table 4).
In the Maintenance Phase, subjects who discontinue from the study for any reason prior to 
completing Week 48 will complete an ET Visit conducted as close as possible to the time of study 
discontinuation. If study discontinuation occurs at the regularly scheduled visit (eg, Maintenance 
Phase Week 36) the ET Visit/procedures should be performed. These subjects will also have 2 
Safety Follow-up Visits (at 8 and 16 weeks) after final IP administration for the assessment of 
safety and clinical status after exiting the study. For subjects who are permanently discontinued 
from IP during the Maintenance Phase and remain in the study to complete safety and efficacy 
assessments, the Interim and Final Safety Follow-up Visits will be conducted at 8 and 16 weeks, 
respectively, after their last study visit in the Maintenance Phase. Assessments should be 
performed in accordance to the schedule of events (Table 5).
In the OLE Phase, subjects who discontinue the study will have an OLE-ET/EoT Visit within 2
weeks after final CC-93538 administration and an Interim and Final 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 schedule of events 
(Table 6).
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 
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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. 
11.4
Emergency Identification of Investigational Products
The blind must not be broken during the course of the study unless in the opinion of the 
investigator, it is absolutely necessary to safely treat the subject. If it is medically imperative to 
know what IP the subject is receiving, IP should be temporarily discontinued if, in the opinion of 
the investigator, continuing IP can negatively affect the outcome of the subject’s treatment.
The decision to break the blind in emergency situations remains the responsibility of the treating 
physician, which will not be delayed or refused by the Sponsor. However, the investigator may 
contact the Medical Monitor prior to breaking the blind to discuss unblinding, mainly in the interest 
of the subject. 
The investigator should ensure that the code is broken only in accordance with the protocol. The 
investigator should promptly notify the Medical Monitor of the emergency unblinding and the 
reason for breaking the blind, which should be clearly documented by the investigator in the 
subject’s source documentation.
Emergency unblinding should only be performed by the investigator through the IWRS by using 
an emergency unblinding personal identification number (PIN), and the investigator should call 
IWRS for unblended dose information.
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12
REGULATORY CONSIDERATIONS
12.1
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative, and 
investigator abide by Good Clinical Practice (GCP), as described in International Council on 
Harmonisation (ICH) Guideline E6 and in accordance with the general ethical principles outlined 
in the Declaration of Helsinki. The study will receive approval from an IRB/EC prior to 
commencement. The investigator will conduct all aspects of this study in accordance with 
applicable national, state, and local laws of the pertinent regulatory authorities.
12.2
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in the 
local regulations. Celgene staff or an authorized representative will evaluate and approve all 
investigators who in turn will select their staff.
The investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions, 
including obligations of confidentiality of Celgene information. The investigator should maintain 
a list of Sub-investigators and other appropriately qualified persons to whom he or she has 
delegated significant study-related duties.
The investigator is responsible for keeping a record of all subjects who sign an informed consent 
form (ICF /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 themselves to acknowledge their willingness 
to continue in the study.
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 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, 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 
applicable. Amendments that are administrative in nature do not require IRB/IEC approval but 
will be submitted to the IRB/IEC for information purposes.
12.6
Institutional Review Board/Independent Ethics Committee Review and 
Approval
Before the start of the study, the study protocol, ICF/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 
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sought. If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements.
Investigational product 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.
12.8
Termination of the Study
Celgene reserves the right to terminate this study prematurely at any time for reasonable medical 
or administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc).
In addition, the investigator or Celgene has the right to discontinue a single site at any time during 
the study for medical or administrative reasons such as:
•
Unsatisfactory enrollment;
•
GCP noncompliance;
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•
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 IP 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/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.
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The investigator must obtain approval in writing from Celgene prior to destruction of any records. 
If the investigator is unable to meet this obligation, the investigator must ask Celgene for 
permission to make alternative arrangements. Details of these arrangements should be 
documented. 
All study documents should be made available if required by relevant health authorities. The 
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 details describing strategy, 
including definition of study critical data items and processes (eg, risk-based initiatives in 
operations and quality such as risk management and mitigation strategies and analytical risk-based 
monitoring), methods, responsibilities, and requirements, including handling of noncompliance 
issues and monitoring techniques (central, remote, or on-site monitoring) are provided in the 
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 
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product was transferred to the responsibility of the investigational site (eg, during manufacturing, 
packaging and labeling, storage, and/or distribution).
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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APPENDIX A
TABLE OF ABBREVIATIONS
Table 8:
Abbreviations and Specialist Terms
Abbreviation or Specialist 
Term
Explanation
ADA 
Anti-drug antibody
ADL
Activity of daily life
AE
Adverse event
AESI 
Adverse event of special interest
ALT
Alanine aminotransferase (SGPT)
ANCOVA 
Analysis of covariance
aPTT 
Activated partial thromboplastin time
AST
Aspartate aminotransferase (SGOT)
AUC
Area under the curve
β-hCG 
β-subunit of human chorionic gonadotropin
CI 
Confidence interval
Cmax
Observed maximum serum concentration
CMH 
Cochran-Mantel-Haenszel
COVID-19 
Coronavirus disease 2019
CPK 
Creatine phosphokinase
CRF
Case report form
CRP 
C-reactive protein
CSR
Clinical study report
Ctrough 
Serum trough concentration
DMC
Data Monitoring Committee
DNA 
Deoxyribonucleic acid
DSD
Dysphagia Symptom Diary
EC
Ethics Committee
ECG
Electrocardiogram
ECP
Eosinophil cationic protein
eCRF 
Electronic case report form
EDC 
Electronic data capture system
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Table 8:
Abbreviations and Specialist Terms
Abbreviation or Specialist 
Term
Explanation
EG
Eosinophilic gastritis
EGD 
Esophagogastroduodenoscopy
EGE
Eosinophilic gastroenteritis
EGID
Eosinophilic gastrointestinal disorder
EGPA
Eosinophilic granulomatosis with polyangiitis
EoE 
Eosinophilic esophagitis
eos 
Eosinophils
EoT
End of Treatment
ePRO 
Electronic patient-reported outcome
ET 
Early Termination
FCBP 
Female of childbearing potential
Fc
Fragment, crystallizable
FDA
Food and Drug Administration
FGID
Functional gastrointestinal disorders
GCP
Good Clinical Practice
GGT 
Gamma glutamyltransferase
GI 
Gastrointestinal
H&E 
Hematoxylin and eosin
HBcAb 
Hepatitis B core antibody
HBsAg 
Hepatitis B surface antigen
HBV 
Hepatitis B virus
hct 
Hematocrit
HCV 
Hepatitis C virus
HES
Hypereosinophilic syndrome
hgb 
Hemoglobin
HFI
Hereditary fructose intolerance
HIV
Human immunodeficiency virus
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Table 8:
Abbreviations and Specialist Terms
Abbreviation or Specialist 
Term
Explanation
hpf 
High-power field
IB
Investigator’s Brochure
ICE
Intercurrent event
ICF
Informed consent form
ICH
International Council for Harmonisation
IE 
Intercurrent event
IFNα 
Interferon alpha
IgE 
Immunoglobulin E
IgG 
Immunoglobulin G
IgG1
Immunoglobulin G1
IgG1κ 
Immunoglobulin G1 kappa
IGRA 
Interferon gamma release assay
IL
Interleukin
IL-13Rα1 
Interleukin-13 receptor alpha 1
IL-13Rα2 
Interleukin-13 receptor alpha 2
INR 
International normalized ratio
IP
Investigational product
IRB
Institutional Review Board
ISR 
Injection site reaction
ITT
Intent-to-treat
IUD
Intrauterine device
IUS 
Intrauterine hormone-releasing system
IV
Intravenous
JAK
Janus kinase
IWRS 
Interactive Web Response System
JIDC
Japan Intractable Diseases Center
KM
Kaplan-Meier 
LSM 
Least squares mean
mAb 
Monoclonal antibody
MAR 
Missing at random
MCH 
Mean corpuscular hemoglobin
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Table 8:
Abbreviations and Specialist Terms
Abbreviation or Specialist 
Term
Explanation
MCHC 
Mean corpuscular hemoglobin concentration
MCV 
Mean corpuscular volume
MHLW
Japan Ministry of Health, Labour and Welfare
MI 
Multiple imputation
OLE 
Open-label Long-term Extension
PFS 
Pre-filled syringe(s)
PIN
Personal identification number
PK
Pharmacokinetic(s)
PPI 
Proton pump inhibitor
PRO 
Patient-reported outcome
PT 
Prothrombin time
RANTES
Regulation upon Activation Normal T-cell Expressed and Secreted
RBC
Red blood cell 
RNA 
Ribonucleic acid
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
SE 
Standard error
SGOT
Serum glutamic oxaloacetic transaminase 
SGPT
Serum glutamic pyruvic transaminase
SI 
International System of Units
SMT 
Safety Management Team
SOP
Standard Operating Procedure
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Table 8:
Abbreviations and Specialist Terms
Abbreviation or Specialist 
Term
Explanation
SUSARs
Suspected unexpected serious adverse reactions
t½
Terminal elimination half-life
TB 
Tuberculosis
TEAE 
Treatment-emergent adverse event
Th2
T-helper type 2
tmax
Time to the observed maximum concentration
TNFα 
Tumor necrosis factor alpha
ULN
Upper limit of normal
US 
United States
VAS
Visual analog scale
WBC
White blood cell
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APPENDIX B
IZUMO SCALE 
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Reference (English version)
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APPENDIX C
EGID SEVERITY SCORE (FOR AGES ≥ 20 YEARS OLD)
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Reference (English version)
Adult symptom score scoring table
Decision in one month immediately preceding
40 points or more severe, 15-39 points moderate, 14 points or less mild
Symptoms typical of the upper gastrointestinal tract (1) Vomiting
3 points: Nausea present (no vomiting)
5 points: 1 time per day vomiting 4 days or more in a month
7 points: 2-5 times/day vomiting 4 days or more in a month
9 points: 6 times / day or more vomiting 1 day or more per month
Symptoms typical of the upper gastrointestinal tract (2) Dysphagia
6 points: Always has difficulty swallowing
9 points: Experienced food press-fitting or endoscopic removal
Symptoms typical of the upper gastrointestinal tract (3) Loss of appetite
6 points: Don't always have an appetite
9 points: Almost no appetite and requires tube feeding etc.
Abdominal pain
3 points: Mild, short time, no restrictions on activity
6 points: Moderate, long lasting every day, or occurring after sleep
9 points: Severe, always pain requiring the use of painkillers
Symptoms typical of the lower gastrointestinal tract (1) Diarrhea
3 points: 2-5 watery stools more than 4 days a month
6 points: 6 or more watery diarrhea 4 days or more in a month
9 points: Dehydration occurred.
Symptoms typical of the lower gastrointestinal tract (2) Bloody stool
3 points A small amount of blood is mixed at least once a month
6 points: Obvious bloody stool at least once a month
9 points: Large amounts of bloody stools every day
Laboratory findings (choose the minimum value)
3 points: 3.0 ≤ Alb <3.5
6 points: 2.0 ≤ Alb <3.0
9 points: Alb <2.0
Peripheral blood eosinophil ratio (choose maximum)
3 points: 5% or more and less than 10%
6 points: 10% or more and less than 20%
9 points: 20% <
So far, surgery has been performed to eliminate complications of EGlDs (perforation, 
stenosis, etc.)
0 points: No
5 points: Yes
Have you used steroids, immunosuppressive drugs, or other drugs of concern for side 
effects in the past year for the treatment of EGlDs?
0 points: Not used
5 points: Used
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APPENDIX D
EGID SEVERITY SCORE (FOR AGES FROM 2 TO 19 YEARS 
OLD)
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Reference (English version)0
Symptom score scoring table for ages 2-19 years old
Decision in one month immediately preceding
40 points or more severe, 15-39 points moderate, 14 points or less mild
General condition (probable deterioration due to EGIDs)
0 points: Good condition, no action restrictions
3 points: Age-appropriate behavior is more restricted than usual
6 points: Poor condition and often restricted behavior
10 points: There is a clear delay in development
Weight
0 points: Weight gain or stability
3 points: Can't gain weight
6 points: Weight <-2SD
9 points: Weight <-3SD
Height
0 points: -1SD ≤ height
  3 points: -2SD ≤ height <-1SD
(Do not count if there is no problem from the height of parents)
6 points: Height <-2SD
9 points: First height <-3SD
Symptoms typical of the upper gastrointestinal tract (1) Vomiting
0 points: No nausea
3 points: Nausea present (no vomiting) 4 days or more per month
5 points: 1 time per day vomiting 4 days or more in a month
7 points: 2-5 times/day vomiting 4 days or more in a month
Symptoms typical of the upper gastrointestinal tract (2) Dysphagia
0 points: Can swallow food normally
3 points: Difficulty swallowing 4 or more times per month
6 points: Always has difficulty swallowing
9 points: Experienced food press-fitting or endoscopic removal
Symptoms typical of the upper gastrointestinal tract (3) Loss of appetite
0 points: Appetite present
3 points: 4 days or more a month with no appetite
6 points: Don't always have an appetite
9 points: Almost no appetite and requires tube feeding etc.
Abdominal pain
0 points: No abdominal pain
3 points: Mild, short time, no restrictions on activity
6 points: Moderate, long lasting every day, or occurring after sleep
9 points: Severe, always pain requiring the use of painkillers
Symptoms typical of the lower gastrointestinal tract (1) Diarrhea, number of times per day
0 points: Up to 0-1 watery stools
3 points: 2-5 watery stools more than 4 days a month
6 points: 6 or more watery stools a day or more
9 points: Dehydrated and required IV drip
Symptoms typical of the lower gastrointestinal tract (2) Bloody stools, number of times per day
0 points: No bloody stools
3 points: At least once with a small amount of blood
6 points: 1 or more obvious bloody stools
9 points: Large amounts of bloody stools every day
Laboratory findings
0 points: No abnormality in albumin (Alb) or hemoglobin (Hb)
3 points: 3.0 ≤ Alb <3.5, and / or 9.0 ≤ Hb <11.0
6 points: Alb <3.0 and/or Hb <9.0
9 points: Alb <2.0 and/or Hb <7.0
Peripheral blood eosinophil ratio
0 points: 0 to less than 5%
3 points: 5% or more and less than 10%
6 points: 10% or more and less than 20%
9 points: 20% or more
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APPENDIX F
PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 4.0, 07-Dec-2022:
Protocol Amendment 4.0 is created to correct inconsistencies in the document and provide 
administrative changes.
Summary of Changes for Protocol Amendment 4.0
Section Number & Title
Description of Change
Brief Rationale
Medical 
Monitor/Emergency 
Contact Information
Change in address of Bristol-
Myers Squibb K.K.
Updated contact information of 
Medical Monitor due to Bristol-
Myers Squibb K.K. headquarters 
relocation
Title Page and Signature 
Pages
Personnel changes
Administrative changes
Title Page
Removed Investigational New 
Drug (IND) number
Removed IND number since this 
clinical trial is not actually 
planned to be submitted to the 
United States Food and Drug 
Administration
Title Page
Protocol Summary 
Section
Section 1.2.1: 
Mechanism of Action
Added Bristol-Myers Squibb 
(BMS) compound number 
(BMS-986355)
For clarification purposes
Section 1.2.2.4: Phase 1 
Study, CC-93538-CP-
002
New section added
A new section was added to 
include the results of Study CC-
93538-CP-002, which provides 
the pharmacokinetic (PK) 
comparability, safety, tolerability, 
and immunogenicity of a single 
subcutaneous (SC) dose of 360 
mg CC-93538 using 2 different 
drug concentrations, 180 mg/mL 
and 150 mg/mL, in healthy adult 
subjects
Table 6: Table of Events 
for the Open-label Long-
term Extension (OLE)
Added language that the first 
dose with the 360 mg/2.0 mL 
pre-filled syringe (PFS) 
presentation will be 
administered during an in-
For the OLE Phase, the CC-
93538 SC dose with single 
injection of 360 mg/2.0 mL PFS 
will be implemented in order to 
study the higher concentration 
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Summary of Changes for Protocol Amendment 4.0
Section Number & Title
Description of Change
Brief Rationale
Section 7.2: Treatment 
Administration and 
Schedule
clinic visit in the OLE Phase 
to ensure accurate dose 
administration and 
compliance
and higher volume presentation 
for use with long-term CC-93538 
treatment
Section 1.3.2.1: Benefit-
Risk Assessment
Added information related to 
concomitant use of 
coronavirus disease 2019 
(COVID-19) vaccines in 
subjects receiving CC-93538
Updates made to clarify that non-
live COVID-19 vaccinations are 
allowed and considered as a 
simple concomitant medication 
within the study, and details such 
as type and date of vaccine 
received should be recorded on 
the COVID-19 Vaccination Form
Section 1.3.2.1: Benefit-
Risk Assessment
Added text to clarify that the 
overall safety profile of CC-
93538 remains consistent with 
the information that has been 
presented in the Investigator's 
Brochure (IB).
For clarification purposes
Protocol Summary
Section 3.2: Study 
Duration for Subjects
Added text to clarify that 
"post-marketing clinical 
study" will be used to refer to 
this study following market 
approval in Japan
Added a sentence to clarify that 
this study will continue until 
market launch and then be 
converted to “post-marketing 
clinical study” after the marketing 
approval date in Japan
Section 4.2: Inclusion 
Criteria
In criterion 1, changed the age 
of the subject for whom a 
proxy consent is required 
from under 20 years old to 
under 18 years old
Updates made to reflect a change 
that the age of majority in Japan 
has been reduced from 20 to 18 
years old due to the Civil Code 
amendment
Section 4.2: Inclusion 
Criteria
Section 6: Procedures
Deleted the sentence “for 
subjects aged from 18 to 19 
years, assent is not necessarily 
required if the patient is 
considered to have a level of 
understanding comparable to 
that of adults by the 
investigator”
The sentence is no longer needed 
since the Civil Code amendment 
lowered the age of majority from 
20 to 18 years old
Section 4.2: Inclusion 
Criteria
Updated criterion 7 in that a 
female subject who has 
undergone bilateral 
salpingectomy is not 
Updated definition of an FCBP to 
keep consistency across CC-
93538 study protocols
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Summary of Changes for Protocol Amendment 4.0
Section Number & Title
Description of Change
Brief Rationale
considered a female of 
childbearing potential (FCBP)
Section 4.3: Exclusion 
Criteria
Clarified in criterion 8 that 
corticosteroids are allowed as 
background or rescue therapy
For clarification purposes
Systemic corticosteroids at stable 
doses (up to 10 mg/day of 
prednisone) are allowed in this 
study
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Summary of Changes for Protocol Amendment 4.0
Section Number & Title
Description of Change
Brief Rationale
Section 6.1: Screening 
Period
Removed the detailed 
description regarding a human 
immunodeficiency virus 
(HIV) antibody confirmation 
assay methodology
Revision due to methodology 
change for HIV antibody 
confirmation assay performed in a 
central laboratory in accordance 
with the recommendation of 
World Health Organization 
(WHO) guidelines for HIV 
testing strategy
Table 4: Table of the 
Events for the Induction 
Phase
Table 5: Table of the 
Events for the 
Maintenance phase
Table 6: Table of Events 
for the Open-label Long-
term Extension (OLE)
 
 
 
measured at all applicable 
visits after Day 1 which the 
EGID severity scoring is 
scheduled
Considering that different score 
scales are used for patients under 
20 years of age, 
 
 
 
 to assess the EGID severity 
score more accurately
Section 7.1: Description 
of Investigational 
Product(s)
Added note to clarify 
“investigational product” in 
this protocol will 
automatically be replaced 
with “post-marketing clinical 
study drug” on and after the 
date of marketing approval in 
Japan
At the same time that this study is 
converted to ͆post-marketing 
clinical study” after the marketing 
approval date in Japan, the 
investigational product will be 
also replaced with post-marketing 
clinical study drug
Section 7.1: Description 
of Investigational 
Product(s)
Section 7.2.1: Self-
Administration
Added new text related to 
"Instructions of Use" 
document
For clarification purposes
Section 8.1: Permitted 
Concomitant 
Medications and 
Procedures
Table 7: Medications, 
Diets, or Procedures 
Requiring Stable Dosing 
Regimens or Restricted 
Added permitted concomitant 
use of PPIs for indications 
other than EGE
Corrections made to resolve in-
document inconsistency
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Summary of Changes for Protocol Amendment 4.0
Section Number & Title
Description of Change
Brief Rationale
Use Prior to Study 
Enrollment
Section 9.6.2: Subgroup 
Analyses
Updated language regarding 
subgroup analyses
Updates made to align with the 
Statistical Analysis Plan (SAP)
Section 9.6.3.1: Analyses 
Methods
Added language regarding the 
Fisher’s exact test
Updates made to clarify and to 
align with the SAP
Section 9.7: Safety 
Analysis
Provided clarification that the 
overall safety and tolerability 
data will be summarized by 
presentation utilizing 
descriptive statistics
Text added to describe the 
assessment of the safety profile of 
CC-93538 based on PFS 
presentation that the subjects will 
receive during the study
Section 10.5: Reporting 
of Serious Adverse 
Events
Revised sentence related to 
SAE report to require all 
SAEs occurring after the time 
of signing the informed 
consent form (ICF)/assent to 
be reported to Celgene Drug 
Safety
Changes made to align with the 
company requirements
All
Minor formatting, 
typographical corrections, and 
revisions for clarity
Corrections made to resolve in-
document inconsistency
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Summary of Changes CC-93538-EG-001
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Protocol CC-93538-EG-001 Amendment 3 Final: 28 Oct 2021 
1.
JUSTIFICATION FOR AMENDMENT
Significant changes included in this amendment are summarized below:
Addition of 180 mg/mL pre-filled syringe (PFS) in the Open-label Long-term Extension
(OLE) Phase
A newly developed CC-93538 180 mg/mL formulation is added for use in the OLE Phase in 
addition to the currently used 150 mg/mL formulation.
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Protocol CC-93538-EG-001 Amendment 3 Final: 28 Oct 2021 
Revised sections: 
!
Protocol Summary
!
Section 7 Description of Study Treatments
Section 7.1 Description of Investigational Product(s)
References:
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Protocol CC-93538-EG-001 Amendment 2 Final 27 Aug 2021
1.
JUSTIFICATION FOR AMENDMENT
Addition of an extra specimen for gastric/duodenal biopsies
Updated to allow an additional sample to be obtained based on the investigator’s judgment in 
order to secure the flexibility of gastric/duodenal biopsies in the evaluation of eosinophil count.
Revised section: 
!
Section 6.4 Efficacy Assessment 
The amendment also includes another minor change
!
Replacement of Clinical Trial Physician (Medical Monitor/Emergency Contact 
Information)
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Protocol CC-93538-EG-001 Amendment 2 Final 27 Aug 2021
!
Change of Sponsor Address
!
Correction of typographical errors
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Protocol CC-93538-EG-001 Amendment 1 Final: 29 Jun 2021
1.
JUSTIFICATION FOR AMENDMENT
Significant changes included in this amendment are summarized below:
Change of Patient-Reported Outcome (PRO) from 
 to Izumo Scale
The primary purpose of this protocol amendment is to change the key PRO to assess
gastrointestinal (GI) symptom of Japanese patients with Eosinophilic Gastroenteritis (EGE). 
 
 
 
 
On the other hand, the Izumo scale was developed as a questionnaire 
 
 with the past 7 days gastrointestinal symptoms with Japanese language as 
an original. Izumo Scale was confirmed useful as a disease-specific 
 assessment 
scale for Japanese patients with gastrointestinal symptoms (Furuta, 2009). Since this study is a 
study conducted only in Japanese patients with EGE, weekly assessment by Izumo scale was 
considered more appropriate in this study than 
for a key secondary endpoint.
Therefore, the PRO instrument for this study has been changed from the 
 to the 
Izumo Scale.
Procedures to enhance subject adherence to questionnaire completion have also been modified to 
clarify alarm and surveillance were kept and telephone call reminders have been removed, since 
daily assessments have changed to weekly assessments.
Revised sections: 
!
Protocol Summary
!
Section 2 Study Objectives and Endpoints (Tables 2 and 3)
!
Section 3.1 Study Design (Section 3.1.1 Screening Period, Section 3.1.2 Induction 
Phase)
!
Section 4.2 Inclusion Criterion #4
!
Section 5 Tables of Events
!
Section 6.1 Screening Period
!
Section 6.2 Induction Phase and Maintenance Phase
!
Section 6.3 Follow-up Period
!
Section 6.4 Efficacy Assessment (Section 6.4.2.1 Izumo Scale Questionnaire)
!
Section 9.6 Efficacy Analysis (Section 9.6.3.1 Analyses Methods)
!
Appendix B
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EDMS Doc. Number: 25576315 - 25577215
CC-93538
Summary of Changes CC-93538-EG-001
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Protocol CC-93538-EG-001 Amendment 1 Final: 29 Jun 2021
Recategorization of secondary endpoints
To clarify that clinical symptoms of EGE are assessed using the Izumo Scale as an axis, clinical 
response using Eosinophilic Gastrointestinal Disorder (EGID) Severity Score is moved from Key 
Secondary Endpoint to Secondary Endpoint in the Induction and Maintenance Phases. 
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EDMS Doc. Number: 25576315 - 25577215
CC-93538
Summary of Changes CC-93538-EG-001
Celgene International II Sàrl
Confidential and Proprietary
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Protocol CC-93538-EG-001 Amendment 1 Final: 29 Jun 2021
Revised sections: Protocol Summary, Section 2 Study Objectives and Endpoints (Table 2), 
Section 5 Tables of Events, Section 6.1 Screening Period
Update of timeframe of endpoints
The timeframe of Weeks 30 to 32 in study endpoints is removed from the endpoints timeframes
to focus on assessments at end of each phase (Week 16/Induction Phase and Week 
48/Maintenance Phase).
Please note that the timeframes in the Tables of Events are not changed.
Revised section: Section 2 Study Objectives and Endpoints (Table 2)
Update of main symptoms of EGE
Vomiting as a major symptoms was replaced by nausea based on recent findings (Dellon, 2019).
Revised sections: Protocol Summary, Section 1.1 Disease Background
Update of definition of histologic evidence of EGE
The criteria for evidence of EGE (≥ 30 eosinophils [eos]/high-power field [hpf] in at least 5 hpf 
in the stomach and/or ≥ 30 eos/hpf in at least 3 hpf in the duodenum while on stable background 
therapy) was clarified in this amendment.
Revised section: Protocol Summary, Section 3.1.2,Section 4.2 Inclusion Criterion #3
Update of examples of any other disease listed in Exclusion Criterion #5
Gastritis and enterocolitis are removed from examples of 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, to clarify eligible patients.
Revised sections: Section 4.3 Exclusion Criterion #5
Addition of definition of hypereosinophilic syndrome (HES)
The definition of HES is added to clarify eligible patients.
Revised section: Section 4.3 Exclusion Criterion #5
Revised section: Section 5 Tables of Events 
Clarification of Esophagogastroduodenoscopy (EGD) Procedure
The EGD Procedure is clarified such that biopsies for the Open-label Long-term Extension
(OLE) Day 1/Baseline will be read in a blinded manner.
Revised section: Section 6.4.1 Esophagogastroduodenoscopy (EGD)
Addition of the statistical method of time-to-event data
The analyses method of time-to-event data is added to clarify the statistical approach.
Revised section: Section 9.6.3.1 Analyses Methods
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EDMS Doc. Number: 25576315 - 25577215
CC-93538
Summary of Changes CC-93538-EG-001
Celgene International II Sàrl
Confidential and Proprietary
6
Protocol CC-93538-EG-001 Amendment 1 Final: 29 Jun 2021
The amendment also includes several other minor clarifications and corrections
!
Clarification of definition of adolescent (Protocol Summary and Section 6)
!
Update of coronavirus disease 2019 (COVID-19) vaccine language (Section 1 and 
Section 8)
!
Correction of timeframe of study endpoints (Section 2, Tables 2 and 3)
!
Addition of footnote to Inclusion Criterion #1 (Section 4.2)
!
Addition of height timepoint for adolescent to calculate EGID Severity Score 
(Section 5)
!
Update of EGID Severity Score due to the release of Japan EGID guideline (Section 
6.4, Appendix C, and Appendix D)
!
Clarification to the Early Termination Visits in the Maintenance Phase and in the 
Open-label Long-term Extension Phase.(Section 3, Section 5, Section 6, and Section 
7.2)
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Change of language accompanying protocol template update (Section 10.1, Section 
14.1, Section 14.3)
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Correction of administrative language (Section 10.4, Section 14.1)
!
Addition and revision of references (Section 16)
!
Update of Abbreviations and Specialist Terms (Appendix A)
!
Correction of in-document links 
!
Correction of typographical errors
References:
Dellon ES, Peterson KA, Murray JA, Falk GW, Gonsalves N, Chehade M, et al. AK002 
(Antolimab) in Adult Patients with Active Eosinophilic Gastritis and/or Eosinophilic 
Gastroenteritis: Primary Results from a Randomized, Double-Blind, Placebo- Controlled Phase 2 
Trial (ENIGMA; NCT03496571). Poster presented at: ACG 2019; October 25th - 30th 2019; San 
Antonio, TX.
Furuta K, Ishihara S, Sato S, Miyake T, Ishimura N, Koshino K, et al. Shoukaki Shoujou wo 
yuusuru Kanja no QOL Hyouka no tame no Monshinhyou. “Izumo Scale” no Sakusei to sono 
Kensyou (Development and verification of the Izumo Scale, new questionnaire for quality of life 
assessment of patients with gastrointestinal symptoms). Nihon Shoukakibyouhgakkai Zasshi (J 
Japanese Society of Gastroenterol). 2009: 106; 1478-87. (published in Japanese)
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