Clinical trial NCT04753697
Conditions: Eosinophilic Esophagitis
Keywords: Eosinophilic Esophagitis CC-93538 RPC4046 Adult Adolescent Gastrointestinal Diseases Esophagitis Gastroenteritis Eosinophils Eosinophilia Esophageal Diseases Allergic Diseases Antibody, Monoclonal Hypersensitivity Immunologic factors Physiological Effects of Drugs cendakimab
Sponsor: Celgene
Start date: 2021-02-22; Completion date: 2024-08-29
Enrollment: 430 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Study CC-93538-EE-001 is a Phase 3, multicenter, multinational, randomized, double-blind, placebo-controlled induction and maintenance study to evaluate the efficacy and safety of CC- 93538 in adult and adolescent participants with eosinophilic esophagitis (EoE). The study will incorporate a 24-week Induction Phase followed by a 24-week Maintenance Phase.

Participants will be randomized at the beginning of the study into 3 treatment arms:

* Placebo for Induction and Maintenance
* CC-93538 360 mg Subcutaneous (SC) once weekly for Induction followed by 360 mg SC once every other week for Maintenance
* CC-93538 360 mg SC once weekly for Induction and Maintenance

Detailed description:

Arms: arm 1: CC-93538 360 mg Subcutaneously (SC) once weekly for 24 weeks followed by CC-93538 360 mg SC once weekly for 24 weeks arm 2: CC-93538 360 mg SC once weekly for 24 weeks followed by CC-93538 360 mg SC once every other week for 24 weeks.

During the Maintenance Phase, matching placebo will be administered once every other week on alternate weeks to maintain the blind. arm 3: Matching placebo SC once weekly for 24 weeks followed by matching placebo SC once weekly for 24 weeks
Interventions: intervention 1: CC-93538 intervention 2: Placebo
Intervention descriptions: intervention 1: Subcutaneous intervention 2: Subcutaneous

Protocol documents:
Prot_SAP_000.pdf: 
Official Title of Study: 
A Phase 3, 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 Eosinophilic Esophagitis 
 
NCT Number: NCT04753697 
Document Date (Date in which document was last revised): 01 September 2023 
 
 
 


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
1
A PHASE 3, 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 EOSINOPHILIC ESOPHAGITIS PAGE
PROTOCOL NUMBER:
CC-93538-EE-001
DATE FINAL:
30-Sep-2020
AMENDMENT 0.1 UK
01-Apr-2021
AMENDMENT 0.1 DE
23-Apr-2021
ADDENDUM 1.2 JP
10-Jun-2021
AMENDMENT 0.1 ES
13-Sep-2021
ADMINISTRATIVE LETTER No. 01
04-Mar-2022
AMENDMENT 1.0
01-Sep-2023
EudraCT NUMBER:
2020-004336-16
IND NUMBER:
119240
SPONSOR NAME / ADDRESS:
Celgene International II Sàrl
Route de Perreux 1
2017 Boudry
Switzerland
CONFIDENTIAL
This protocol is provided to you as an Investigator, potential Investigator, 
or consultant for review by you, your staff, and ethics 
committee/institutional review board.  The information contained in this 
document is regarded as confidential and, except to the extent necessary 
to obtain informed consent, may not be disclosed to another party unless 
such disclosure is required by law or regulations.  Persons to whom the 
information is disclosed must be informed that the information is 
confidential and may not be further disclosed by them.
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
2
MEDICAL MONITOR / EMERGENCY CONTACT INFORMATION
The PPD Medical Monitoring team can be reached by contacting the PPD Safety Hotline.
24/7 PPD Medical Monitor Safety Hotline
North American Regional 
Contact
EMEA & APAC Regional 
Contact
Phone:
Phone:
Fax:
Fax:
Sponsor Clinical Trial Physician
Title:
 Clinical Trial Physician, 
Address: 3401 Princeton Pike, Lawrenceville, NJ 08648
Phone: 
E-mail: 
The back-up 24-hour global emergency contact call center should only be used if you are not 
able to reach the PPD Medical Monitor(s) or Clinical Trial Physician(s) or designee for 
emergency calls.
Back-up 24-hour Global Emergency Contact Call Center: 
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
3
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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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
4
SPONSOR:  CELGENE INTERNATIONAL II SÀRL
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
5
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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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
6
COORDINATING PRINCIPAL INVESTIGATOR SIGNATURE PAGE
Signature of Coordinating Principal Investigator
dd mmm yyyy
Printed Name of Coordinating Principal Investigator
Institution Name:_______________________________________
By my signature, I agree the protocol has been written to comply with ICH Good Clinical 
Practices guidelines and agree to offer guidance throughout the study as needed.
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
7
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 1.0:
The purpose of this amendment is to update the statistical methodology, revise the study 
discontinuation criteria
, 
, as well as align this protocol with guidance provided across the 
development program. Please note that country-specific restrictions are added to this global 
protocol amendment, and any country specific protocol amendments will be retired. 
Other edits were made throughout the protocol to correct minor errors, add clarity, and improve 
consistency and alignment. The Protocol Summary was updated to reflect changes in the 
amendment.
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 1.0
Section Number & 
Title
Description of Change
Brief Rationale
Title Page and Signature 
Pages

Updated 
Sponsor 
address 
and 
personnel.

Administrative changes.
Section 1:1: Disease 
Background: 
Eosinophilic Esophagitis

Added approval for dupilumab in the 
United States (US).

To provide updated information on 
an approved treatment for EoE.
Section 1.2.1: 
Mechanism of Action

Added 
Bristol
Myers 
Squibb
Company (BMS) compound number.

For clarification purposes.
Section 1.2.2: Clinical 
Studies

Updated the list of CC-93538 clinical 
studies with additional studies.

To provide further information on 
clinical studies in the CC-93538 
development program.
Section 1.2.2.2 Phase 2 
Study, CC-93538-AD-
001

Added new protocol section for Study 
CC-93538-AD-001.

To include a brief description of the 
Phase 2 Study CC-93538-AD-001 
evaluating CC-93538 for moderate-
to-severe atopic dermatitis.
Section 1.2.2.5: Phase 1 
Study, CC-93538-CP-
002

Added new protocol section for Study 
CC-93538-CP-002.

To include the results of Study 
CC-93538-CP-002, which provide 
the pharmacokinetic comparability, 
safety, 
tolerability, 
and 
immunogenicity 
of 
a 
single 
subcutaneous 
dose 
of 
360 mg 
CC-93538 using 2 different drug 
concentrations, 
180 mg/mL 
and 
150 mg/mL, 
in 
healthy 
adult 
subjects.
Section 1.2.2.6: Phase 1 
Study, IM042-003

Added new protocol section for Study 
IM042-003.

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 AI versus PFS.
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
8
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 1.0
Section Number & 
Title
Description of Change
Brief Rationale
Section 1.3.1.1: Benefit-
Risk Assessment
Section 8.1: Permitted 
Concomitant 
Medications and 
Procedures

Added 
information 
related 
to 
concomitant 
use 
of 
coronavirus 
disease of 2019 (COVID-19) vaccines 
in subjects receiving CC-93538.

Non-live COVID-19 vaccinations 
will be allowed and will be 
documented 
as 
a 
concomitant 
medication for this study. The 
efficacy and safety of non-live 
vaccines 
(including 
non-live 
COVID-19 vaccines) in subjects 
receiving 
CC-93538 
remain 
unknown currently.
Section 1.3.2: Rationale 
for the Study Design

Added information related to the 
advisory panel of patients and 
caregivers.

Administrative update.
Table 3: Study 
Endpoints: Maintenance 
Phase Endpoints at 
Week 48

Added a secondary endpoint to 
evaluate the proportion of subjects 
who
maintained 
their histologic 
response at Week 24 to Week 48.

To provide additional results on 
maintenance of response.
Table 1: Study 
Objectives
Table 2: Study 
Endpoints: Induction 
Phase Endpoints at 
Week 24
Table 3: Study 
Endpoints: Maintenance 
Phase Endpoints at 
Week 48
Table 4: Table of Events 
for the Induction Phase
Table 5: Table of Events 
for the Maintenance 
Phase 
Section 6.2: Induction 
Phase and Maintenance 
Phase Treatment Period
 
 
 
 
 
 
 
 
 
 
Section 3.1: Study 
Design
Section 4.1: Number of 
Subjects

Added language regarding study 
eligibility, clarifying that in Germany, 
Spain, and the United Kingdom, only 
subjects who have had an inadequate 
response to corticosteroids or are 

Local 
restrictions 
prohibit 
enrollment of subjects who are naive 
or have had an adequate response to 
corticosteroids in Germany, Spain, 
and the United Kingdom.
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
9
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 1.0
Section Number & 
Title
Description of Change
Brief Rationale
Section 4.2: Inclusion 
Criteria
Section 12.3: Subject 
Information and 
Informed Consent
intolerant to corticosteroids will be 
enrolled in the Phase 3 Studies.

Updated language to indicate that in 
Austria, 
Germany, 
Spain, 
and 
Switzerland, adolescent subjects will 
not be included in the Phase 3 Studies.

Local 
restrictions 
prohibit 
enrollment of adolescent subjects in 
Germany and Spain. Adolescents 
will not be enrolled in Austria or 
Switzerland as participating sites in 
these countries do not serve the 
adolescent patient population or have 
decided to only enroll adult patients.
Section 4.2: Inclusion 
Criteria

Updated Inclusion Criterion 8) to 
indicate that women that have had 
bilateral
salpingectomy 
are also 
considered to be not of childbearing 
potential.

Notes included regarding restrictions 
on acceptable methods of hormonal 
contraception in Japan

Added to clarify that women that 
have had a bilateral salpingectomy 
are not of childbearing potential.

Added clarification based on local 
restrictions included in the Japan 
country-specific protocol addendum.
Section 4.3: Exclusion 
Criteria

Added clarification to Exclusion 
Criterion
22) 
for 
a 
known 
hypersensitivity to any ingredient in
the investigational product.

Added clarification based on local 
restrictions included in the Japan 
country-specific protocol addendum.   
Section 6.2: Induction 
Phase and Maintenance 
Phase Treatment Period

Provided guidance regarding the 
Week 24 dose when out of window 
due to EGD scheduling.

For clarification.
Section 6.2.1 EoE Flare 
Assessment Visit

Provided guidance regarding Week 
24/Week 48 Visit EGD requirements 
for subjects that had an EGD as part 
of their EoE Flare assessment. 

Note added to clarify samples do not 
need to be a pre-dose draw unless the 
subject is expected to dose later that 
day.

For clarification. 
Section 6.4.1: 
Esophagogastroduode-
noscopy (EGD)

Added clarification for handling 
incidental 
findings 
of 
potential 
clinical relevance not associated with 
objectives of the study.

Provide additional guidance on 
handling of incidental findings found 
on the EGD. 
Section 6.4.2.1: 
Modified Daily 
Symptom Diary (mDSD)

Added guidance for diary completion 
during transition between phases or 
studies.

For clarification.
Section 6.4.2.8: 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 study.

Language 
for 
entry 
into 
the 
Maintenance Phase was updated to 
clarify that this decision should be 
made in conjunction with the 
Medical Monitor.
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
10
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 1.0
Section Number & 
Title
Description of Change
Brief Rationale
Section 7.2: Treatment 
Administration and 
Schedule

Added language from the Germany 
country-specific protocol amendment 
that required 60-minute post-dose 
observation.

To add language from the Germany 
country-specific 
protocol 
amendment.
Section 7.2.1: Self-
Administration

Added language from the Japan 
country-specific protocol addendum
that provides additional clarification 
about self-administration.

To add language from the Japan 
country-specific protocol addendum.
Section 7.2.4: Guidelines 
for Temporary 
Interruption of Dosing

Added guidance, consistent with 
Study CC-93539-EE-002, on how to 
manage subjects who test positive for 
COVID-19 during the treatment 
period.

To align with guidance in Study CC-
93538-EE-002. 
Section 8: Concomitant 
Medications and 
Procedures
Section 8.1: Permitted 
Concomitant 
Medications and 
Procedures

Added 
information 
related 
to 
concomitant 
use 
of 
COVID-19 
vaccines in subjects who receive CC-
93538.

Non-live COVID-19 vaccinations 
will be allowed and will be 
documented 
as 
a 
concomitant 
medication for this study. The 
efficacy and safety of non-live 
vaccines 
(including 
non-live 
COVID-19 vaccines) in subjects 
receiving 
CC-93538 
remain 
unknown at this time.
Section 8.2: Prohibited 
Concomitant 
Medications and 
Procedures

Added 
further 
examples 
of 
immunomodulating drugs.

Also added language to clarify that 
corticosteroids can be used for an EoE 

For clarification.
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 1.0
Section Number & 
Title
Description of Change
Brief Rationale
flare, or used for an adverse event 
(AE) with consultation with the 
Medical Monitor, and will not result 
in permanent discontinuation of IP.
Section 9.1: Overview

Added details for database lock and 
the clinical study report.

For clarification.
Section 9.2: Study 
Population Definitions
9.6.1: Efficacy Analysis 
of the Co-primary 
Endpoints

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 9.3: Sample Size 
and Power 
Considerations

Updated this section using more 
accurate estimates from the Phase 2 
study 
(RPC02-201) 
and 
recent 
published literature, and clarified the 
significance level (alpha).

Updated to reflect more accurate 
estimates and clarify significance 
level (alpha).
Section 9.6.1.1: 
Overview of Attributes 
of the Main Estimand for 
the Co-primary 
Endpoints

Updated the section title and included 
the main estimands for the co-primary 
endpoints in table format.

Updated the main estimand for the co-
primary endpoint of change in 
dysphagia days (DD) from baseline to 
Week 24. The estimand strategy to 
handle intercurrent events (ICEs) of 
rescue therapy/prohibited medication 
use has been changed from the 
treatment policy estimand strategy to 
the composite variable estimand 
strategy.

Tables were added to conform with 
the Sponsor’s internal protocol 
template regarding the presentation 
of estimand.

Main estimand strategy was updated 
as the composite variable estimand 
strategy, which reflects treatment 
failure, 
is 
considered 
a 
more 
appropriate strategy for handling 
rescue/prohibited medication use 
than the treatment policy estimand 
strategy for the main estimand.
Section 9.6.1.2: Change 
in Dysphagia Days (DD) 
from Baseline to Week 
24 (Induction Phase)

Included language stating how DD are 
calculated.

Included 
language 
defining 
the 
missing data rule.

Added a sensitivity analysis where a 
minimum of 4 measurable diary days 
per week is required to derive a DD 
score for the 14-day period.

Removed a sensitivity analysis where 
missing daily DD scores are imputed 
using multiple imputation (MI).

Added a supplementary analysis for 
the co-primary endpoint of change in 
DD from baseline to Week 24 using 
the treatment policy estimand strategy 
to 
handle 
ICEs 
of 
rescue 
therapy/prohibited medication use.
 
 
 
 

Sensitivity analysis was removed as 
it was considered to provide very 
little additional insight beyond the 
currently specified sensitivity and 
supplementary analyses.

Main estimand strategy was updated 
from treatment policy estimand 
strategy 
to 
composite 
variable 
estimand strategy for handling ICEs 
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
12
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 1.0
Section Number & 
Title
Description of Change
Brief Rationale
of 
rescue 
therapy/prohibited 
medication use.
Section 9.6.1.3: 
Eosinophilic Histologic 
Response at Week 24 
(Induction Phase)

Updated language to indicate that 
missing data for the binary efficacy 
endpoints will be imputed using the 
MI 
approach 
rather 
than 
non-
responder imputation.
 
Section 9.6.1.3: 
Eosinophilic 
Histological Response at 
Week 24 (Induction 
Phase)
Section 9.6.3: Analysis 
of Secondary Efficacy 
Endpoints
Section 9.6.4.1: 
Analyses Method

Removed language stating that the 
stratified 
Newcombe 
confidence 
interval (CI) will be provided for 
binary efficacy endpoints.  

The method for handling missing 
data for the binary efficacy endpoints 
has 
been 
changed 
from 
non-
responder 
imputation 
to 
MI; 
therefore, the Newcombe CIs cannot 
be provided. 
Section 9.6.2: Analysis 
of Key Secondary 
Efficacy Endpoints

Added supplemental analyses using 
the treatment policy estimand strategy 
to 
handle 
ICEs 
of 
rescue 
therapy/prohibited medication use.
 
Section 9.6.4: Control of 
the Type I Error Rate

Added language and updated the 
hierarchical testing procedure to 
include two secondary endpoints at 
Week 48 in the overall population and 
testing of the co-primary endpoints 
and two secondary endpoints at Week 
48 
in 
the 
Steroid 
Inadequate 
Responders/Intolerant subgroup.

Updated for consistency 
 
 to 
align with development objectives.
Section 9.6.5: Subgroup 
Analyses

Added “on stable dietary modification 
(eg, elimination diet for the treatment 
of allergy or EoE [yes versus no])” to 
the list of subgroups that will be 
assessed.

Removed 
language 
regarding 
a 
criterion for conducting the subgroup 
analyses.

Added to better understand CC-
93538 treatment response in the 
presence of other EoE concomitant 
therapies.

Language was removed as this 
information will be specified and 
discussed in the statistical analysis 
plan.
Section 10.5: Reporting 
of Serious Adverse 
Events

Modifications 
were 
made 
for 
reporting of serious adverse events 
(SAEs) that occur prior to treatment 
but after signing the informed consent 
form/assent. 

All SAEs must be reported to 
Celgene Drug Safety within 24 hours 
of the Investigator’s knowledge of 
the event by completing in EDC. 
Section 10.6: Adverse 
Events of Special 
Interest

Added text denoting the Sponsor will 
also identify Adverse Events of 

For clarification.
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
13
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 1.0
Section Number & 
Title
Description of Change
Brief Rationale
Special 
Interest 
(AESI) 
programmatically.

Clarified that AESIs must be entered 
into EDC.
Section 10.7: Expedited 
Reporting of Adverse 
Events

Gastroesophageal 
reflux 
disease 
(GERD) and dysphagia are not 
considered anticipated serious events, 
and as such they will not be excluded 
from expedited reporting of AEs to 
the United States Food and Drug 
Administration per the CC-93538 
Safety Surveillance Plan.

Per the Safety Surveillance Plan for 
CC-93538, following review of data 
from randomized controlled trials in 
EoE, including Study RPC02-201, 
anticipated severe events have not 
been identified for the EoE patient 
population; therefore, dysphagia and 
GERD are being removed as serious 
anticipated events from the CC-
93538-EE-001 protocol.
Section 11.2: Study 
Discontinuation

Removed 
reasons 
other 
than 
withdrawal of consent (WOC) and 
lost to follow-up (LTFU) as reasons
why subjects discontinue from study. 
Death and Other remain as they are 
standard.

 since 
subjects can continue on study 
without being on investigational 
product, the main reasons for 
subjects to discontinue from the 
study should be due to Lost to 
Follow-Up (LTFU) or Withdrawal of 
Consent (WOC).
Section 14.3: 
Investigational 
Medicinal Product 
Quality Issues

An Investigator Memo was provided 
in 2021 to inform sites of the new
process on reporting any issues with 
investigational 
product 
and 
this 
language is now reflected in this 
amendment.

Updated to reflect the current 
internal processes.
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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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
14
PROTOCOL SUMMARY
Study Title
A Phase 3, 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 Eosinophilic Esophagitis
Indication
CC-93538, also known as BMS-986355 (nonproprietary name, cendakimab), is a recombinant 
humanized, high-affinity neutralizing (immunoglobulin G1 kappa [IgG1κ]) monoclonal antibody 
(mAb) selective for interleukin-13 (IL-13).  CC-93538 binds to IL-13, thus preventing its 
interaction with both IL-13 receptors, IL-13 receptor alpha 1 (IL-13Rα1) and IL-13 receptor alpha 
2 (IL-13Rα2).  Eosinophilic esophagitis (EoE) is a chronic immune/antigen-mediated esophageal 
disease characterized clinically by symptoms related to esophageal dysfunction and histologically 
by eosinophil-predominant inflammation, and IL-13 has been shown to be a key driver of disease 
pathology in patients with EoE.
Globally, the Phase 3 program includes a multicenter, multinational, randomized, double-blind, 
placebo-controlled induction and maintenance study to evaluate the efficacy and safety of CC-
93538 in adult and adolescent subjects with EoE (Study CC-93538-EE-001) with a separate, 
optional Open-Label Extension Study (OLE; Study CC-93538-EE-002). However, in Germany, 
Spain, and the United Kingdom, only subjects who have had an inadequate response to 
corticosteroid therapy or are intolerant to corticosteroid therapy will be enrolled in the studies.
Also, in Austria, Germany, Spain, and Switzerland, adolescent subjects will not be enrolled.
Results of the Phase 2 Study, RPC02-201, in adult subjects with EoE showed that administration 
of CC-93538 180 mg and 360 mg subcutaneously (SC) weekly for 16 weeks reduced the mean 
esophageal eosinophil count (the primary endpoint) and improved other inflammatory parameters.  
A greater reduction in dysphagia symptoms was observed with the 360 mg dose although it did 
not reach statistical significance. The study also demonstrated the safety and tolerability of CC-
93538 in adult subjects with symptomatic EoE treated with one of 2 dose levels (CC-93538 180 
mg or 360 mg SC) compared to placebo.  CC-93538 was generally safe and well tolerated for up 
to 68 weeks of treatment (including data from a 52-week CC-93538 Open-Label Extension).  
These data support the continued development of CC-93538 as a novel treatment for EoE.  The 
single pivotal Phase 3 study is designed to confirm and extend the findings obtained from the 
positive Phase 2 study with CC-93538.  
Objectives (Primary and Secondary)
Primary Objectives

To assess the efficacy of CC-93538 versus placebo in reducing dysphagia symptoms at 24 
weeks

To assess the efficacy of CC-93538 versus placebo in reducing esophageal eosinophil counts 
at 24 weeks
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
15
Secondary Objectives

To assess the efficacy of CC-93538 versus placebo at 24 weeks in improving:

Endoscopic features of EoE 

Histologic features of EoE

To assess the persistence of effect of CC-93538 at 48 weeks in reducing:

Dysphagia symptoms

Esophageal eosinophil counts

To assess the persistence of effect of CC-93538 through administration of a less frequent 
dosing regimen at 48 weeks in reducing:

Dysphagia symptoms

Esophageal eosinophil counts

To assess the persistence of effect of CC-93538 at 48 weeks in improving:

Endoscopic features of EoE 

Histologic features of EoE

To evaluate the time to and frequency of EoE flare events and use of rescue therapy during the 
study

To evaluate the safety and tolerability of CC-93538 including the characterization of the 
immunogenicity profile

To assess trough concentrations of CC-93538 in subjects with EoE
See Section 2 for a complete list of study objectives, including all 
 objectives.
Study Endpoints (Primary and Secondary)
Induction Phase Endpoints
For endpoints listed below with statistical comparisons, the CC-93538 360 mg SC once weekly 
treatment arm (2 active arms combined) will be compared to the placebo arm.
Co-primary endpoints at Week 24:  

The mean change in dysphagia days (DD), evaluated over the prior 14-day period using the 
modified Daily Symptom Diary (mDSD), from baseline to Week 24

The proportion of subjects with eosinophilic histologic response defined as a peak esophageal 
eosinophil count < 6/high-power field (hpf) at Week 24
Key secondary endpoints at Week 24:

The proportion of subjects with eosinophilic histologic response defined as a peak esophageal 
eosinophil count < 15/hpf at Week 24

The mean change in the endoscopic features of EoE as measured by the EoE Endoscopic 
Reference Score (EREFS) from baseline to Week 24 
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
16

The mean change in the mean adjusted histology grade score as measured by the EoE histology 
scoring system (EoEHSS) from baseline to Week 24

The mean change in the mean adjusted histology stage score as measured by the EoE histology 
scoring system (EoEHSS) from baseline to Week 24

The mean change in the modified Daily Symptom Diary (mDSD) composite score from 
baseline to Week 24

Additional secondary endpoints at Week 24:

The proportion of subjects with a ≥ 50% decrease in dysphagia days (DD) from baseline at 
Week 24

The mean change in dysphagia days (DD) over time from baseline through Week 24

The mean change in the modified Daily Symptom Diary (mDSD) composite score over time 
from baseline through Week 24

The time to event of EoE flare during the Induction Phase

The time to event of use of rescue therapy during the Induction Phase

The proportion of subjects with an EoE flare during the Induction Phase

The proportion of subjects with use of rescue therapy during the Induction Phase

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

Measurements of trough concentrations of CC-93538 in subjects with EoE during the 
Induction Phase
Maintenance Phase Endpoints
For endpoints listed below with statistical comparisons, the 2 CC-93538 dosing regimens (360 mg 
SC once weekly and 360 mg SC once every other week) will be compared to placebo separately.
Secondary endpoints at Week 48:

The mean change in dysphagia days (DD), evaluated over the prior 14-day period using the 
modified Daily Symptom Diary (mDSD), from baseline to Week 48

The proportion of subjects with eosinophilic histologic response defined as a peak esophageal 
eosinophil count ≤6/hpf at Week 48

The proportion of subjects with eosinophilic histologic response defined as a peak esophageal 
eosinophil count < 15/hpf at Week 48

The mean change in the endoscopic features of EoE as measured by the EoE Endoscopic 
Reference Score (EREFS) from baseline to Week 48 

The mean change in the mean adjusted histology grade score as measured by the EoE histology 
scoring system (EoEHSS) from baseline to Week 48

The mean change in the mean adjusted histology stage score as measured by the EoE histology 
scoring system (EoEHSS) from baseline to Week 48
1.0
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930207646
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Approved
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
17

The mean change in the modified Daily Symptom Diary (mDSD) composite score from 
baseline to Week 48

The proportion of subjects with eosinophilic histologic response defined as a peak esophageal 
eosinophil count ≤ 6/hpf at Week 48 among subjects with eosinophilic histologic response
defined as a peak esophageal eosinophil count ≤ 6/hpf at Week 24

The time to event of EoE flare during the study (Induction and Maintenance Phases)

The time to event of use of rescue therapy during the study (Induction and Maintenance Phases)

The proportion of subjects with an EoE flare during the study (Induction and Maintenance 
Phases)

The proportion of subjects with use of rescue therapy during the study (Induction and 
Maintenance Phases)

Safety and tolerability evaluated by the incidence, severity, and relationship to CC-93538 of 
AEs, SAEs, clinical laboratory abnormalities, changes in vital signs, physical examination 
abnormalities, and the presence of anti-drug antibodies

Measurements of trough concentrations of CC-93538 in subjects with EoE during the 
Maintenance Phase
See Section 2 for a complete list of study endpoints including all 
 endpoints.
Study Design
Study CC-93538-EE-001 is a Phase 3, 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.  The study will incorporate a 24-week Induction 
Phase followed by a 24-week Maintenance 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 24-week Induction Phase.  Subjects (N ≈ 
399) will be randomized (1:1:1) to receive CC-93538 360 mg subcutaneously (SC) once weekly 
(2 of the 3 treatment arms) or matching placebo, in a double-blind manner for 24 weeks.  Subjects 
are required to have at least 4 dysphagia days (DD) as assessed with the dysphagia modified Daily 
Symptom Diary (mDSD) over the prior 2 consecutive weeks (14 days) before baseline and 
histologic evidence of EoE, defined as a peak count of ≥ 15 eosinophils per hpf at any 2 levels 
(proximal, mid, distal) of the esophagus; both assessments will be conducted when not receiving
anti-inflammatory therapy.  Further, eligibility also includes a previous proton pump inhibitor trial 
without a complete response.  Treatment assignment at baseline will be stratified based on steroid 
responder status to ensure an equal balance in the treatment arms. 
After completion of Week 24 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 EoE flare (refer to Section 6.4.2.7).  The Maintenance Phase treatment arms include 360 
mg SC once every week, 360 mg SC once every other week, and matching placebo.  
Approximately half of the subjects receiving CC-93538 360 mg SC once weekly during the 
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
18
Induction Phase will continue on the same dosing regimen for the Maintenance Phase while the 
other half of the subjects will continue on the less frequent regimen of 360 mg SC once every other 
week per the original randomization assignment.  Subjects previously randomized to placebo will 
remain on placebo.
Clinical laboratory tests, vital signs, physical examinations (including height and weight),
pregnancy tests, esophagogastroduodenoscopy (EGD), clinical symptom assessment, subject-
reported outcomes, serum CC-93538 concentrations, serum antibodies to CC-93538 (to assess 
immunogenicity), concomitant medications, and AE assessments will be performed according to 
the Table of Events presented in Table 4 (Induction Phase) and Table 5 (Maintenance Phase).  
Subjects experiencing an EoE flare in the Induction or Maintenance Phase may continue to 
participate with concomitant rescue therapy as needed and will be eligible to enter the Open-Label 
Extension (OLE) study only following completion of Week 24 of the Induction Phase or Week 48
of the Maintenance Phase, respectively. Subjects with an EoE flare requiring rescue therapy 
during the Induction Phase will not be eligible to enter the Maintenance Phase.
Following Induction, subjects not entering the Maintenance Phase or OLE study will return for an 
Interim and a Final Safety Follow-up Visit at 8 and 16 weeks, respectively, after final 
investigational product (IP) administration for the assessment of safety and clinical status. 
Similarly, subjects completing the Maintenance Phase who do not participate in the OLE study 
will complete the Interim and the 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.
The study will be conducted in compliance with International Council for Harmonisation (ICH) 
Good Clinical Practices (GCPs).
Study Population
The study population will consist of males and females aged 12 to 75 years (inclusive) with EoE 
who have had an inadequate response to corticosteroid therapy or are intolerant to corticosteroid 
therapy, 
as 
defined 
in 
Section 4.2, 
Inclusion 
Criterion
5
(Steroid 
Inadequate 
Responders/Intolerant; approximately 70% of the study population) as well as subjects who are 
naïve or have had an adequate response to corticosteroid therapy (Steroid Responders/Naïve; 
approximately 30% of the study population).  Approximately 369 adults (aged 18 to 75 years) and 
30 adolescents (aged 12 to 17 years) with a weight of ≥ 40 kg will be enrolled in the study.
However, in Germany, Spain, and the United Kingdom, only subjects who have had an inadequate 
response to corticosteroid therapy or are intolerant to corticosteroid therapy will be enrolled in the 
study. In Austria, Germany, Spain, and Switzerland, adolescent subjects will not be enrolled.
Note:  Countries or sites with local restrictions that prohibit enrollment of adolescents (aged 12 to 
17 years inclusive) will only enroll subjects who are 18 years of age or older.  Enrollment of 
adolescent subjects will begin only after the applicable regulatory requirements for enrolling 
subjects in that age group have been satisfied and the necessary health authority approvals have 
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
19
been granted.  Where national or regional guidelines for the definition of adolescence differ from 
the definition stated above, the national or regional guidelines may be used to determine eligibility.
Length of Study
The maximum duration of subject participation in this study is approximately 72 weeks.  Subjects 
will participate up to 4 weeks in the Screening Period (the screening EGD may be completed up 
to 8 weeks prior to Day 1), 24 weeks in the Induction Phase Treatment Period, and 24 weeks in 
the Maintenance Phase Treatment Period of the study.  Following Induction, subjects not entering 
the Maintenance Phase or OLE study will have Interim and Final Safety Follow-up Visits (at 8 
and 16 weeks) after final IP administration for the assessment of safety and clinical status. 
Similarly, subjects completing the Maintenance Phase who do not participate in the OLE study 
will have Interim and Final Safety Follow-up Visits (at 8 and 16 weeks) after final IP 
administration; for these subjects, the maximum duration is approximately 71 weeks.  However, 
as an exception, the maximum duration of participation will be approximately 72 weeks for 
subjects permanently discontinuing IP during the Maintenance Phase but who continue study 
participation through Week 48, as the Interim and Final Safety Follow-up Visits will occur 8 and 
16 weeks after the last study visit instead of the last dose of IP.
The End of Study is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up, or the date of receipt of the last data point from the last subject that is 
required for primary, secondary,
 analysis, as pre-specified in the protocol, 
whichever is the later date.
Study Treatments
Subjects will be randomized 1:1:1 to the following treatment arms for the 24-week Induction and 
24-week Maintenance Phases:

CC-93538 360 mg SC once weekly for 24 weeks followed by CC-93538 360 mg SC once 
weekly for 24 weeks

CC-93538 360 mg SC once weekly for 24 weeks followed by CC-93538 360 mg SC once 
every other week for 24 weeks.  During the Maintenance Phase, matching placebo will be 
administered once every other week on alternate weeks to maintain the blind. 

Matching placebo SC once weekly for 24 weeks followed by matching placebo SC once 
weekly for 24 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). Matching placebo will also be administered as 2 injections 
of 1.2 mL.
Overview of Key Efficacy Assessments

Number of dysphagia days (DD) and modified Daily Symptom Diary (mDSD) composite score 
using the mDSD instrument

Enumeration of esophageal eosinophil count (peak esophageal eosinophil count) by analysis 
of hematoxylin and eosin (H&E) stained esophageal biopsies
1.0
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
20

EoE Endoscopic Reference Score (EREFS)

EoE histology scoring system (EoEHSS)
For additional detail about key efficacy assessments, please refer to the Table of Events (Table 4
and Table 5).
Overview of Key Safety Assessments

Type, frequency, severity, seriousness, and relationship of AEs to IP

Clinically significant changes in vital signs, physical examinations, and laboratory findings 

Presence of and clinical effects of anti-drug antibodies (ADAs)
For additional detail about key safety assessments, please refer to the Table of Events (Table 4 and
Table 5).
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 (Section 9), will be provided 
in the Statistical Analysis Plan (SAP).  In addition, the statistical analysis and analysis population 
for the European Union (EU) will be described in the SAP.
Sample Size
A total sample size of 399 subjects (266 subjects for CC-93538 and 133 subjects for placebo) with 
a 20% dropout rate at the end of the Induction Phase (212 subjects for CC-93538 and 106 subjects 
for placebo) will provide at least 90% power to detect a difference of -2.79 change in DD from 
baseline at Week 24 and at least 90% power to detect a difference of 15% at Week 24 in histologic 
response with a two-sided significance level (alpha) of 0.05. These calculations were based on a 
2 sample t-test assuming a pooled standard deviation (SD) of 4.76 for change in DD from baseline 
and the chi-square test to compare the difference in 2 independent proportions for the histologic 
response assuming a true placebo response proportion is 0.05.
Efficacy Analysis
Change in DD:  The mean change in DD, evaluated over the prior 14-day period using the mDSD, 
from baseline to Week 24 is one of the 2 co-primary endpoints for the Induction Phase. The 
primary analysis will be conducted on the ITT population based on an analysis of covariance 
(ANCOVA) model with treatment group, Steroid Inadequate Responders/Intolerant status (yes or 
no), and baseline DD values included in the model. The comparison between CC-93538 360 mg 
SC once weekly and placebo for change in DD from baseline at Week 24 will be made using the 
difference in least squares (LS) Mean at a 5% 2-sided significance level.  Point estimates for the 
mean difference between the 2 treatment groups using the adjusted LS Mean changes and 
corresponding 95% Wald CI will be reported. In addition, adjusted LS Means with standard error 
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
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(SE), arithmetic means with standard deviation (SD), and arithmetic mean changes with SD will 
be summarized by treatment group. 
Histologic Response: The other co-primary endpoint, the eosinophilic histologic response is 
defined as a peak esophageal eosinophil count ≤ 6/hpf at Week 24. The primary analysis of the 
eosinophilic histologic response will be conducted on the ITT population using the Cochran-
Mantel-Haenszel (CMH) test at a 2-sided 5% significance level, stratified by Steroid Inadequate 
Responders/Intolerant status. For treatment comparison between CC-93538 360 mg SC once 
weekly and placebo, the 2-sided 95% CI for the difference in proportions using the CMH weights 
and the 2-sided p-value from the CMH test will be provided. 
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 regardless of treatment discontinuation
For ICE number 1, the treatment policy estimand strategy will be used where all observed data 
after the ICE will be included in the primary analysis regardless of the occurrence of the ICE.  For 
ICE number 2, a composite variable estimand strategy will be used where data after rescue therapy
or prohibited medication which may impact the efficacy assessment will be set as non-responders
for histologic response and worst possible value for change in DD.  A missing at random (MAR) 
multiple imputation approach will be applied for missing data.  
Multiplicity Adjustment
A hierarchical testing procedure will be employed to control the overall type I error rate at 0.05 
for the co-primary endpoints, key secondary endpoints, and two secondary endpoints at Week 48
in the overall population. In addition, the hierarchical testing procedure includes testing of the co-
primary endpoints and two secondary endpoints at Week 48 in the Steroid Inadequate 
Responders/Intolerant subgroup. Below is the schematic for this hierarchical testing procedure for 
the United States and other non-European Union regions.
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
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Abbreviations:  DD = dysphagia day(s); EoE = eosinophilic esophagitis; EoEHSS = EoE histology scoring system;
eos = eosinophils; EREFS = EoE Endoscopic Reference Score; hpf = high-power field; ITT = intent-to-treat; mDSD 
= modified daily symptom diary; SIR-I = Steroid Inadequate Responders/Intolerant; WK = week
Note:  p1 and p2 represent the p-values for the 1st co-primary endpoint of change in DD and 2nd co-primary endpoint 
of histologic response, respectively. 
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
23
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.
External Data Monitoring Committee
An external, independent Data Monitoring Committee (DMC) will be convened and will be 
comprised of physician experts with experience in treating subjects with EoE and a statistician, all 
of whom are not otherwise involved in the study conduct and for whom there is no identified 
conflict of interest.  During the study, the DMC will review selected data (to be specified in the 
DMC charter) on a regular basis for the assessment of benefit-risk and determination of study 
continuation.  An independent third party will prepare the reports of aggregate data summaries and 
individual subject data listings, as appropriate, for the DMC members for each scheduled meeting. 
Operational details for the DMC, including 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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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
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TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 1.0:............................................7
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 1.0 ................................7
PROTOCOL SUMMARY ........................................................................................................14
TABLE OF CONTENTS..........................................................................................................24
LIST OF TABLES....................................................................................................................28
LIST OF FIGURES ..................................................................................................................29
1
INTRODUCTION..................................................................................................30
1.1
Disease Background:  Eosinophilic Esophagitis......................................................30
1.2
Investigational Product:  CC-93538 ........................................................................32
1.2.1
Mechanism of Action ..............................................................................................32
1.2.2
Clinical Studies.......................................................................................................33
1.2.2.1
Phase 1 Study, M10-378.........................................................................................33
1.2.2.2
Phase 2 Study, CC-93538-AD-001..........................................................................34
1.2.2.3
Phase 1 Study, RPC02-1901 ...................................................................................34
1.2.2.4
Phase 1 Study, CC-93538-CP-001..........................................................................34
1.2.2.5
Phase 1 Study, CC-93538-CP-002..........................................................................35
1.2.2.6
Phase 1 Study, IM042-003......................................................................................36
1.2.2.7
Phase 2 Study, RPC02-201.....................................................................................36
1.3
Rationale ................................................................................................................38
1.3.1
Study Rationale and Purpose..................................................................................38
1.3.1.1
Benefit-Risk Assessment..........................................................................................39
1.3.2
Rationale for the Study Design................................................................................40
1.3.2.1
Justification of Co-Primary Endpoints....................................................................40
1.3.3
Rationale for Dose, Schedule, and Regimen Selection.............................................41
1.3.4
Rationale for Choice of Comparator Compounds ...................................................42
1.3.5
Rationale for 
 Potential Predictive 
..................42
2
STUDY OBJECTIVES AND ENDPOINTS...........................................................42
3
OVERALL STUDY DESIGN ................................................................................50
3.1
Study Design ..........................................................................................................50
3.1.1
Screening Period ....................................................................................................51
3.1.2
Induction Phase......................................................................................................52
3.1.3
Maintenance Phase.................................................................................................52
3.1.4
Safety Follow-up Visits ...........................................................................................53
3.1.5
Worsening of EoE Symptoms ..................................................................................53
3.2
Study Duration for Subjects....................................................................................54
3.3
End of Study...........................................................................................................54
4
STUDY POPULATION.........................................................................................54
4.1
Number of Subjects ................................................................................................54
4.2
Inclusion Criteria....................................................................................................55
4.3
Exclusion Criteria...................................................................................................57
5
TABLE OF EVENTS.............................................................................................60
6
PROCEDURES......................................................................................................73
6.1
Screening Period.....................................................................................................73
6.1.1
Additional Information Regarding Safety Laboratory Assessments .........................77
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
25
6.1.2
Screening Failures and Rescreening of Potential Subjects ......................................77
6.1.2.1
Rescreening of Subjects Who Develop COVID-19 During the Screening 
Period.....................................................................................................................77
6.2
Induction Phase and Maintenance Phase Treatment Period .....................................78
6.2.1
EoE Flare Assessment Visit ....................................................................................80
6.2.2
End of Treatment/ Early Termination (ET) Visit......................................................81
6.3
Follow-up Period....................................................................................................82
6.3.1
Safety Follow-up Visits (Interim 8-week and Final 16-week)...................................82
6.4
Efficacy Assessment...............................................................................................83
6.4.1
Esophagogastroduodenoscopy (EGD) ....................................................................83
6.4.2
Clinical Symptoms of EoE.......................................................................................85
6.4.2.1
Modified Daily Symptom Diary (mDSD).................................................................85
86
86
86
86
87
6.4.2.7
Worsening of EoE Symptoms, EoE Flare, and the EoE Flare Assessment Visit .......87
6.4.2.8
Entry to Maintenance Phase ...................................................................................88
6.5
Anti-drug Antibody Assessments............................................................................89
6.6
Pharmacokinetics....................................................................................................90
6.6.1
Serum CC-93538 Assessments ................................................................................90
90
90
90
91
91
91
91
91
92
92
92
7
DESCRIPTION OF STUDY TREATMENTS........................................................93
7.1
Description of Investigational Product(s)................................................................93
7.2
Treatment Administration and Schedule .................................................................93
7.2.1
Self-Administration.................................................................................................94
7.2.2
Missed Dose(s) .......................................................................................................95
7.2.3
Dose Adjustments ...................................................................................................95
7.2.4
Guidelines for Temporary Interruption of Dosing...................................................95
7.2.5
Criteria for Discontinuation of Dosing ...................................................................96
7.2.6
Rescue Therapy ......................................................................................................97
7.3
Method of Treatment Assignment...........................................................................97
7.4
Packaging and Labeling..........................................................................................97
7.5
Investigational Product Accountability and Disposal ..............................................98
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7.6
Investigational Product Compliance........................................................................98
8
CONCOMITANT MEDICATIONS AND PROCEDURES....................................98
8.1
Permitted Concomitant Medications and Procedures...............................................99
8.1.1
Rescue Therapy ....................................................................................................100
8.2
Prohibited Concomitant Medications and Procedures............................................100
8.3
Required Concomitant Medications and Procedures..............................................102
9
STATISTICAL CONSIDERATIONS ..................................................................102
9.1
Overview..............................................................................................................102
9.2
Study Population Definitions ................................................................................103
9.3
Sample Size and Power Considerations.................................................................103
9.4
Background and Demographic Characteristics......................................................104
9.5
Subject Disposition...............................................................................................104
9.6
Efficacy Analysis..................................................................................................104
9.6.1
Efficacy Analysis of the Co-primary Endpoints.....................................................104
9.6.1.1
Overview of Attributes of the Main Estimand for the Co-primary Endpoints .........104
9.6.1.2
Change in Dysphagia Days (DD) from Baseline to Week 24 (Induction 
Phase) ..................................................................................................................106
9.6.1.3
Eosinophilic Histologic Response at Week 24 (Induction Phase) ..........................106
9.6.2
Analysis of Key Secondary Efficacy Endpoints......................................................107
9.6.3
Analysis of Secondary Efficacy Endpoints.............................................................108
9.6.4
Control of the Type I Error Rate...........................................................................109
9.6.5
Subgroup Analyses ...............................................................................................111
9.7
Safety Analysis.....................................................................................................111
9.8
Interim Analysis ...................................................................................................112
9.9
Other Topics.........................................................................................................112
9.9.1
Pharmacokinetics, 
 and 
Immunogenicity ....................................................................................................112
112
9.9.3
Internal Safety Management Team........................................................................112
9.9.4
External Data Monitoring Committee...................................................................112
9.9.5
Steering Committee...............................................................................................113
10
ADVERSE EVENTS............................................................................................113
10.1
Monitoring, Recording and Reporting of Adverse Events .....................................113
10.2
Evaluation of Adverse Events...............................................................................114
10.2.1
Seriousness...........................................................................................................114
10.2.2
Severity/Intensity ..................................................................................................115
10.2.3
Causality ..............................................................................................................116
10.2.4
Duration...............................................................................................................116
10.2.5
Action Taken.........................................................................................................116
10.2.6
Outcome ...............................................................................................................116
10.3
Abnormal Laboratory Values................................................................................117
10.4
Pregnancy.............................................................................................................117
10.4.1
Females of Childbearing Potential .......................................................................117
10.5
Reporting of Serious Adverse Events....................................................................118
10.5.1
Safety Queries ......................................................................................................118
10.6
Adverse Events of Special Interest........................................................................118
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10.7
Expedited Reporting of Adverse Events................................................................119
11
DISCONTINUATIONS .......................................................................................120
11.1
Treatment Discontinuation....................................................................................120
11.2
Study Discontinuation ..........................................................................................121
11.3
Emergency Contact...............................................................................................122
11.4
Emergency Identification of Investigational Products ...........................................122
12
REGULATORY CONSIDERATIONS.................................................................123
12.1
Good Clinical Practice..........................................................................................123
12.2
Investigator Responsibilities .................................................................................123
12.3
Subject Information and Informed Consent...........................................................124
12.4
Confidentiality......................................................................................................124
12.5
Protocol Amendments...........................................................................................124
12.6
Institutional Review Board/Independent Ethics Committee Review and 
Approval ..............................................................................................................125
12.7
Ongoing Information for Institutional Review Board/ Ethics Committee ..............125
12.8
Termination of the Study ......................................................................................126
13
DATA HANDLING AND RECORDKEEPING...................................................126
13.1
Data/Documents ...................................................................................................126
13.2
Data Management.................................................................................................126
13.3
Record Retention..................................................................................................126
14
QUALITY CONTROL AND QUALITY ASSURANCE......................................127
14.1
Study Monitoring and Source Data Verification....................................................127
14.2
Audits and Inspections..........................................................................................128
14.3
Investigational Medicinal Product Quality Issues..................................................128
15
PUBLICATIONS .................................................................................................128
16
REFERENCES.....................................................................................................130
17
APPENDICES......................................................................................................136
APPENDIX A
TABLE OF ABBREVIATIONS...........................................................136
APPENDIX B
MODIFIED DAILY SYMPTOM DIARY (MDSD) .............................141
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LIST OF TABLES
Table 1:
Study Objectives ....................................................................................42
Table 2:
Study Endpoints: Induction Phase Endpoints at Week 24........................43
Table 3:
Study Endpoints:  Maintenance Phase Endpoints at Week 48 .................47
Table 4:
Table of Events for the Induction Phase..................................................60
Table 5:
Table of Events for the Maintenance Phase.............................................67
Table 6:
Medications, Diets, or Procedures Requiring Stable Dosing 
Regimens or Restricted Use Prior to Study Enrollment.........................102
Table 7:
Summary of Attributes of the Main Estimand for the Co-primary 
Endpoint - Change in DD from Baseline at Week 24 ............................105
Table 8:
Summary of Attributes of the Main Estimand for the Co-primary 
Endpoint - Histologic Response at Week 24 .........................................105
Table 9:
Abbreviations and Specialist Terms......................................................136
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LIST OF FIGURES
Figure 1:
Overall Study Schema ............................................................................51
Figure 2:
Multiplicity Adjustment for the US and Other Non-EU Regions...........110
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1
INTRODUCTION
1.1
Disease Background: Eosinophilic Esophagitis
Eosinophilic esophagitis (EoE) is a chronic, debilitating, allergic/immune-mediated disease due to 
chronic esophageal inflammation with the development of dysphagia that affects food intake and 
quality of life. The disease is characterized by symptoms related to esophageal dysfunction and 
by eosinophil-predominant inflammation of the esophageal mucosa.
While eosinophils are present in specific regions of the gastrointestinal (GI) tract, they are not 
normally found in the esophagus.  Patients with EoE demonstrate esophageal tissue infiltration of 
significant numbers of eosinophils and other pro-inflammatory cells, including mast cells and B 
and T lymphocytes (Mulder, 2011), the latter characterized by an enrichment of  CD4+ T 
regulatory and type 2 cytokine producing effector type 2 T helper (Th2) cells (Wen, 2019). This 
infiltrating cellular profile along with over expression of cytokines, particularly interleukin-13 (IL-
13) and interleukin-5 (IL-5), strongly suggests that EoE is a type 2 cell-mediated inflammatory 
disease. Many patients with EoE have other atopic diseases including asthma and food allergies, 
supporting the view that EoE likely represents a disease in which type 2 cells and eosinophils play 
key pathogenic roles (Straumann, 2012). 
Interleukin-13 is a pleotropic cytokine that has been shown to have a critical role in the 
immunopathogenesis of type 2 inflammation characteristic of EoE (Wechsler, 2014). Pre-clinical 
and in vitro modeling have shown that IL-13 is overexpressed in the esophageal mucosa of EoE 
subjects and induces a gene transcript profile that overlaps with the EoE-specific esophageal 
transcriptome (Blanchard, 2007).  Interleukin-13 modulates cellular and molecular pathways 
involved in eosinophil recruitment (Brightling, 2010), esophageal barrier function (Sherrill, 2014), 
and tissue remodeling and fibrosis (Zuo, 2010). Simulated altered expression of IL-13 and 
simulated blockade of IL-13 in animal models have also been shown to cause fluctuations in EoE 
disease status, esophageal function, and other related clinical consequences (Zuo, 2010; Kottyan, 
2014; Rothenberg, 2015a).
The extensive tissue remodeling, including epithelial thickening, and fibrosis that also 
characterizes EoE leads to esophageal stricture and narrowing. Esophageal dysfunction, with 
symptoms of dysphagia (the most common symptom), chest pain and upper abdominal pain, and 
food bolus impaction is a direct consequence of these structural changes (Straumann, 2012). 
Natural history studies and molecular endotype analysis in adults demonstrate that EoE is a 
progressive fibrostenotic disease that, if not treated, usually leads to stricture formation (Shaheen,
2018; Shoda, 2018). The risk of stricture formation is proportional to the duration of untreated 
disease (Schoepfer, 2013; Dellon, 2014). If left untreated, EoE transitions to a more fibrotic state 
that is associated with increased morbidity and further decreased quality of life.
In the United States (US), the prevalence of EoE increases with age and peaks in the age range of 
30 to 44 years (Dellon, 2018a). An internal analysis conducted in March of 2019 using US 
commercial claims data demonstrated an increasing EoE prevalence rate over the last several years 
(MarketScan Database, 2018).  From 2011 to 2017, the prevalence for individuals aged 0 to 64 
years was 4.15 (95% confidence interval [CI]: 4.09 to 4.21) per 10,000 persons in 2011 and 10.73 
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(95% CI: 10.58 to 10.88) per 10,000 persons in 2017.  Further, in 2017, adolescent patients, which 
will be included in the Phase 3 program, made up 10.7% of the total patients with EoE aged 12 to 
64 years. 
In the European Union (EU), the prevalence of EoE was reported to be between 1.4 in 10,000 
persons (Dellon, 2015), and 4.8 in 10,000 persons (Giriens, 2015). A pooled estimate from a meta-
analysis of population-based studies in North America, Europe, and Australia placed the 
prevalence of EoE somewhere in the middle of the range (2.27 per 10,000; 95% CI: 1.34 to 3.60) 
(Arias, 2016).  Further, a rise in the incidence of EoE in multiple countries has been reported 
(Moawad, 2018).  Moreover, an additional meta-analysis of studies mainly conducted in North 
America (US and Canada) and Europe reported a pooled prevalence of 3.42 per 10,000 inhabitants 
with a 95% CI: 2.31 to 4.75 (Navarro, 2019).
Although the definitive etiology of EoE is unknown, several factors that influence the risk of EoE 
have been identified. Eosinophilic esophagitis is a disorder most likely triggered by food and/or 
aeroallergens (de Bortoli, 2017). 
Disease pathogenesis involves activation of epithelial 
inflammatory pathways, impaired barrier function, increased production and/or activity of 
transforming growth factor-β, and induction of allergic inflammation by eosinophils and mast cells 
(Rothenberg, 2015b). 
The diagnosis of EoE is based on symptoms related to esophageal dysfunction, the presence of
eosinophil-predominant inflammation on esophageal biopsy, characteristically consisting of a 
peak value of ≥15 eosinophils per high-power field (or approximately 60 eosinophils per mm2),
and assessment of other causes that may be responsible for, or contributing to, symptoms and 
esophageal eosinophilia, particularly gastroesophageal reflux disease (GERD) (Dellon, 2018b).
The clinical manifestations commonly observed in adults with EoE include dysphagia, food 
impaction, chest pain that is often centrally located and may not respond to proton pump inhibitors
(PPIs), GERD-like symptoms/refractory heartburn, and upper abdominal pain (Kapel, 2008; 
Sgouros, 2006; Gonsalves, 2006; Shoda, 2018). The clinical manifestations of EoE observed in 
adolescents include dysphagia and food impactions (Furuta, 2015).
The management of EoE includes pharmacologic, endoscopic, and dietary interventions, as 
outlined in a 2011 consensus statement (Liacouras, 2011) and guidelines provided by the United 
European Gastroenterology group (Lucendo, 2017).  Response to a trial of PPI therapy was 
previously used to rule out diagnosis of EoE. However, recent studies have demonstrated that the 
demographics, endoscopic features, EoE 
 and gene expression profiles do not reliably 
distinguish EoE from PPI-responsive esophageal eosinophilia. 
Therefore, consensus 
recommendations have now advocated removal of a PPI trial for the purposes of establishing a 
diagnosis of EoE (Dellon, 2018b; Molina-Infante, 2016). Proton pump inhibitors are instead 
viewed as a viable treatment alternative for EoE (through off-label use) with an overall clinical 
response and histologic response rate of 30% to 70% (Lucendo, 2017). Given the ease of 
administration and long-term clinical experience, PPIs have been positioned as a first-line 
pharmacological option for most patients with EoE (Dellon, 2018b; Lucendo, 2017). For patients 
without symptom and histologic improvement after PPI therapy, PPI therapy is discontinued. The 
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current standard of care for both naïve and relapsing patients also includes topical corticosteroids 
(swallowed or inhaled preparations) as first line treatment (as an add-on to PPIs or as stand-alone). 
Overall response rates are 60% to 80%. However, the majority of patients relapse within 1 to 4 
months following discontinuation, requiring additional courses of therapy, and most patients lose 
response even if the steroids are continued long-term. Nevertheless, steroids continue to be 
prescribed mostly off-label. 
Although the orodispersible tablet formulation of budesonide 
(JorvezaTM) was approved in the EU in early 2018 for the treatment of EoE in adults over 18 years 
of age, it is not currently approved in the US. The US Food and Drug Administration (FDA) has 
more recently approved dupilumab as a new treatment for EoE in adults and pediatric patients 12 
years and older, weighing at least 40 kg (US FDA, 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
(defined as a peak esophageal intraepithelial eosinophil count of ≤6 per high-power field) in 
approximately 60% of patients and improvements in symptomatic scores (Dellon, 2022; 
Straumann, 2022). Dupilumab’s approval marks the introduction of the use of biologics in the 
EoE treatment paradigm (Nhu, 2022).
Non-pharmacologic treatment strategies include dietary therapy and endoscopic dilations. Dietary 
therapy usually consists of an elemental formula, a six-food elimination diet (SFED), or targeted 
elimination diet (Dellon, 2012). Challenges to this approach include difficulty in compliance, 
effects on quality of life and social activities because patients have to avoid common foods such 
as milk and gluten (Straumann, 2018), and the frequent need for endoscopies to properly assess 
response to changes in food exposure. Dilation of esophageal strictures has been reported to be 
effective for relieving dysphagia in adults and children with EoE (Lucendo, 2018), but it has no 
effect on underlying inflammation (Schoepfer, 2010; Robles-Medranda, 2010) and is not free of 
procedural complications (Schoepfer, 2014a). Dilation is often reserved for patients who have 
failed other therapy. However, dilation may be required as initial therapy in EoE patients (often 
adults) who have high-grade strictures (Dellon, 2013; Furuta, 2007). 
Despite the recent advances in EoE treatment, significant unmet need still exists for a new and 
effective immunomodulatory treatment with an improved safety and tolerability profile, especially 
for long-term management.
1.2
Investigational Product: CC-93538
1.2.1
Mechanism of Action
CC-93538, also known as BMS-986355 (nonproprietary name, cendakimab), is a recombinant, 
humanized, high-affinity neutralizing (immunoglobulin G1 kappa [IgG1κ]) monoclonal antibody 
(mAb). CC-93538 is highly selective for human IL-13 and was generated by humanization of a 
rodent anti-human IL-13 mAb, which was identified using hybridoma technology through 
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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 
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-13 receptor alpha 1 (IL-13Rα1) and IL-13 receptor alpha 2 (IL-13Rα2)
(Ying, 2010), where IL-13Rα1 and IL-13Rα2 may be implicated in inflammation and in the 
progression of tissue remodeling or fibrosis in EoE, respectively (Doran, 2017; Hershey, 2003; 
Fichtner-Feigl, 2006; Fichtner-Feigl, 2008).  
1.2.2
Clinical Studies
CC-93538 has been investigated in a Phase 1 clinical study in healthy adults and adults with mild-
to-moderate controlled asthma, Study M10-378; a Phase 2 clinical study in adults with moderate-
to-severe atopic dermatitis, Study CC-93538-AD-001; and a Phase 2 clinical study in adults with 
EoE, Study RPC02-201. Additional Phase 1 single-dose pharmacokinetic (PK) studies in adult 
healthy volunteers, RPC02-1901,
CC-93538-CP-001, and CC-93538-CP-002, were also
completed, and preliminary results are available for a fourth PK study, IM042-003 Part 1.
1.2.2.1
Phase 1 Study, M10-378
The PK of CC-93538 was examined in healthy adults (between 18 and 55 years of age, inclusive) 
and adults with mild-to-moderate asthma in Study M10-378. The PK data included results from 
16 healthy subjects after intravenous (IV) infusion over the 0.3 mg/kg to 10.0 mg/kg CC-93538 
dose range, 12 subjects with mild-to-moderate asthma after IV infusion over the 0.3 mg/kg to 10.0 
mg/kg dose range, and 8 subjects with mild-to-moderate asthma after SC administration of 0.3 or 
3.0 mg/kg for 3 weekly doses. After IV administration, the exposures, as determined by CC-93538 
area under the curve (AUC) and observed maximum serum concentration (Cmax), increased in a 
dose-dependent manner and were similar in healthy subjects and subjects with asthma. The 
median time to the observed maximum concentration (tmax) for CC-93538 following SC 
administration in subjects with asthma was approximately 108 hours or 4.5 days. The mean 
estimated volume of distribution at steady state for CC-93538 ranged from 69.7 to 97.7 mL/kg, 
and the mean systemic clearance for CC-93538 ranged from 0.106 to 0.154 mL/hr/kg. The mean 
terminal elimination half-life (t½) for CC-93538 ranged from 16.4 to 26.7 days.  See 
Section 1.2.2.7 for PK results from Phase 2 Study RPC02-201.
In Study M10-378, CC-93538 was well tolerated and had an acceptable safety profile when 
administered as a single dose up to 10.0 mg/kg IV or as 3 weekly doses of 0.3 and 3.0 mg/kg SC. 
There were no deaths.  One serious adverse event (SAE) of bunionectomy which was considered 
unrelated to study drug was reported in a healthy subject.  The adverse event (AE) profile in healthy 
adults was similar to that observed in subjects with asthma. No dose-related increases or 
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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 an ongoing, Phase 2, multicenter, global, randomized, double-blind, 
placebo-controlled, parallel-group study to evaluate the safety and efficacy of CC-93538 in adult 
subjects with moderate-to-severe atopic dermatitis. A total of 220 subjects were randomized in 
the study, and the clinical study conduct is complete. The study results were still being analyzed, 
and the clinical study report (CSR) was not yet final at the time of this 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 elimination 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 antibodies. None of the subjects who had treatment-induced ADAs
had TEAEs suspected by the Investigator to be related to CC-93538.  
There were no deaths, SAEs, AEs leading to discontinuation, or infusion/injection site or 
hypersensitivity reactions.  The most frequently reported (2 or more subjects) TEAEs were 
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.
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 elimination 
t½ of approximately 18.7 to 23.4 days and a small volume of distribution of approximately 7.4 to 
9.8 L were observed.  The 90% CI for the least squares geometric mean ratios for Cmax and AUC 
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from a combined dose analysis were found to be approximately within the typical 80% to 125% 
bound.  These data suggest that the PK of CC-93538 is similar between Japanese and Caucasian 
subjects.
Anti-drug antibodies were detected in 20 of 48 subjects.  Of the 20 subjects (41.7%) with positive 
anti-CC-93538 antibody response, 12 TEAEs were reported; 1 of which (injection site pain) was 
considered by the investigator to be related to study drug.  There was no indication that CC-93538 
exposure was impacted in any of the subjects with positive ADAs, and ADA response did not 
impact the safety of CC-93538 following a single 180 mg or 360 mg SC dose.  There were no 
deaths, SAEs, or TEAEs leading to study discontinuation.  All TEAEs were mild to moderate in 
severity.  The only TEAEs reported in 2 or more subjects included upper respiratory tract infection, 
cough, back pain, headache, and anaemia. Overall, CC-93538 was well tolerated and had an 
acceptable safety profile in healthy Japanese and Caucasian adult subjects following a single SC 
dose of 180 mg or 360 mg.
1.2.2.5
Phase 1 Study, CC-93538-CP-002
Study CC-93538-CP-002 was an open-label, randomized, parallel design study to evaluate the PK 
comparability, safety, tolerability, and immunogenicity of a single SC dose of 360 mg CC-93538 
using 2 different drug concentrations, 180 mg/mL and 150 mg/mL, in healthy adult subjects. A 
total of 52 subjects were enrolled and randomized 1:1 to receive a single 360 mg SC dose of CC-
93538 using either 180 mg/mL (one injection of 2.0 mL) or 150 mg/mL (two injections of 1.2 mL 
each) drug concentrations.
Following SC administration of either the 150 mg/mL or 180 mg/mL concentrations, the statistical 
comparison of PK parameters for CC-93538-CP-002 showed that the point estimate for the ratios 
of geometric least squares means of peak and total exposure parameters for the comparison of 180 
mg/mL versus 150 mg/mL treatments were close to 1 and their 90% CI were contained entirely 
within 80% to 125%, indicating the two formulations were biocomparable. The nonparametric 
analysis of serum CC-93538 tmaxusing Hodges-Lehmann showed the median difference between 
these treatments was not statistically significant.
The two concentration products 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. No differences were observed 
in safety, tolerability, or immunogenicity. Anti-drug antibodies developed on Day 56 or later in 8 
subjects total (5 subjects receiving 150 mg/mL and 3 subjects receiving 180 mg/mL). The ADA 
profiles were similar between subjects receiving 150 mg/mL and 180 mg/mL. There was no 
indication that the ADA response impacted the safety, tolerability, and PK of CC-93538 following 
a single SC dose of 360 mg using either 150 mg/mL or 180 mg/mL. ADAs were not associated 
with differences in safety, tolerability, or PK.
Overall, 17 of 52 subjects (32.7%) reported at least one TEAE. The majority of TEAEs were mild 
to moderate in severity. The most frequent TEAEs reported included injection site bruising (2 
subjects from each treatment group) and coronavirus disease 2019 (COVID-19). No other TEAEs 
were reported in more than one subject.  Overall, only 2 subjects reported at least one TEAE related 
to study drug (frequent bowel movements [one subject from the 150 mg/mL treatment group] and 
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
36
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 autoinjector (AI) versus PFS, 
and to evaluate the PK of CC-93538 when administered by the AI at different injection sites, in 
healthy subjects. A total of 104 subjects were enrolled. In Part 1 of the study, 64 subjects were 
randomized 1:1 to receive CC-93538 360 mg SC either by PFS or by AI in the abdomen. In Part 
2 of the study, 40 subjects were randomized 1:1 to receive CC-93538 360 mg SC by AI in either 
the upper arm or the upper thigh area. Part 2 began enrollment after the completion of Part 1; the 
results of which will be included in the final CSR. 
In Part 1 of the study, following SC administration of CC-93538 360 mg, either by PFS or AI, the 
preliminary statistical comparison of PK parameters showed that the 90% confidence interval (CI) 
for the ratios of geometric least squares means of peak and exposure parameters for the comparison 
of PFS vs AI were contained entirely within 80% to 125%, indicating the 2 devices (PFS and AI) 
are biocomparable. 
Overall, 27 of 64 subjects (42.2%) reported at least one TEAE. There were 14 subjects (43.8%) 
who reported 29 TEAEs after receiving CC-93538 with the PFS and 13 subjects (40.6%) reported 
18 TEAEs after receiving CC-93538 with the AI. The most frequently reported TEAEs were 
arthropod bite (7 subjects), increased alanine aminotransferase (ALT) (5 [7.8%] subjects), and 
headache (4 [6.3%] subjects). Other TEAEs reported in more than one subject included injection 
site erythema, muscle strain, blood creatine phosphokinase (CPK) increased, and constipation.
Except for one event of asymptomatic moderate CPK elevation which was determined not to be 
related to study drug by the Investigator, all TEAEs were mild in severity and were 
recovered/resolved at the end of the study. No deaths or SAEs were reported, and no subject had 
a TEAE that led to early discontinuation from the study. The safety profile of CC-93538 was 
comparable between subjects receiving a single dose of 360 mg/2 mL by PFS or AI. 
Anti-drug antibodies (ADAs) were detected in 10 subjects (4 in the PFS arm and 6 in the AI arm 
[one subject in the AI arm had existing ADAs at baseline]). ADA profiles were similar between 
subjects receiving CC-93538 with the PFS or AI. There was no indication that the ADA response 
impacted the safety, tolerability, or PK of CC-93538 following a single SC dose of 360 mg with 
the PFS or AI. 
The two presentations of CC-93538, given by PFS or AI, administered as a single dose of 360 mg, 
were well tolerated and had an acceptable safety profile in healthy adults. No differences were 
observed in safety, tolerability, or immunogenicity.
1.2.2.7
Phase 2 Study, RPC02-201 
Study RPC02-201 was a Phase 2, multicenter, multinational, randomized, double-blind, placebo-
controlled parallel-group clinical study to evaluate the efficacy and safety of CC-93538 in adult 
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
37
subjects with EoE (Hirano, 2019).  Subjects were stratified 1:1 by previously defined steroid 
refractory status, as determined by the Investigator (47% of enrolled subjects were steroid 
refractory).  After a Screening Period to determine eligibility, adult subjects with EoE were 
randomly assigned in a 1:1:1 ratio to receive either CC-93538 180 mg (N = 31), CC-93538 360 mg 
(N = 34), or placebo (N = 34) weekly for 16 weeks during the double-blind (DB) Treatment Period. 
Subjects received an IV load of either CC-93538 (5 mg/kg or 10 mg/kg) or placebo prior to SC 
dosing.  An optional Open-Label Extension (OLE) for an additional 52 weeks where all subjects 
received 360 mg CC-93538 SC weekly was available for subjects completing the DB Treatment 
Period.  Of the 99 subjects randomized and dosed, 86 (86%) entered the OLE and 66 (66.7%) 
subjects completed Week 52 of the OLE.
In Study RPC02-201, the primary endpoint (changes in esophageal eosinophil count) was met. The 
mean changes from baseline to Week 16 in mean esophageal eosinophil count measured in the 5 
most inflamed high-power fields (hpfs) from the esophageal biopsies in the placebo, CC-93538
180 mg, and CC-93538 360 mg groups were -4.42, -94.76, and -99.90, respectively. The 
difference in mean change from baseline to Week 16 between each CC-93538 group and the 
placebo group was statistically significant (p < 0.0001) for each comparison. Ad hoc analysis 
showed statistically significant differences between both dose groups and placebo in the 
subgroups, subjects known to be steroid-refractory and subjects not known to be steroid-refractory.  
CC-93538 significantly reduced peak esophageal eosinophil count and increased the number of 
subjects with < 15 eosinophils/hpf. CC-93538 also improved inflammatory features of EoE 
including the endoscopic appearance of the esophageal mucosa and improvements in histologic 
changes including fibrosis parameters characteristic of EoE.  
Mean reductions in the subject’s and clinician’s global assessment of disease severity score were 
significant with the 360 mg dose. Improvements in dysphagia symptoms based on mean change 
from baseline to Week 16 in the Dysphagia Symptom Diary (DSD) composite score, as assessed 
by the DSD instrument over the prior 2 weeks were also observed (although not statistically 
significant; the study was not powered for this endpoint) with the 360 mg dose (-6.41 in the placebo 
group compared to -13.31 in the CC-93536 360 mg group). Ad hoc analysis revealed a numerically 
greater decrease in DSD composite score was observed in the CC-93538 360 mg group compared 
with the placebo group for the subgroup of subjects known to be steroid-refractory; however, the 
difference trended toward but did not reach statistical significance (p = 0.0547).  An ad hoc analysis 
of the change from baseline to different time points in the DSD composite score demonstrated 
statistically significant differences between CC-93538 360 mg and placebo at Week 8 (p = 0.0197) 
and Week 12 (p = 0.0460) in subjects known to be steroid refractory.
Long-term treatment with CC-93538 360 mg showed sustained improvements in esophageal 
eosinophil count and other inflammatory features of EoE.  In the OLE, the treatment of subjects 
with weekly CC-93538 360 mg SC doses demonstrated continued improvement in subjects who 
transitioned from placebo and those who originally received the CC-93538 180 mg or 360 mg dose 
in the DB Treatment Period of the study.  
Results from the Phase 2 Study, RPC02-201, suggest that CC-93538 at doses of 180 mg and 
360 mg weekly was well tolerated and had an acceptable safety profile in subjects with EoE.  The 
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
38
most frequently occurring related TEAEs (> 5% in the total CC-93538 group) in the DB Treatment 
Period, shown with incidences in the placebo, CC-93538 180 mg, and CC-93538 360 mg groups, 
respectively, were upper respiratory tract infection (2.9%, 9.7%, 11.8%), headache (8.8%, 9.7%, 
8.8%), and arthralgia (0%, 12.9%, 2.9%).  Injection site reaction TEAEs, were reported for 17.6%, 
12.9%, and 26.5% of subjects in the placebo, CC-93538 180 mg, and CC-93538 360 mg groups, 
respectively.  The most frequently occurring TEAEs in the OLE assessed as at least possibly 
related to study drug (> 3%) were headache and injection site hematoma (4.7% each), and injection 
site erythema, nasopharyngitis, and upper respiratory tract infection (3.5% each).  Injection site 
reaction TEAEs were reported for 18.6% of subjects in the OLE Population.  No deaths were 
reported.  Three subjects experienced 1 SAE each in the DB Treatment Period, including 2 subjects 
in the placebo group (1 with appendicitis and 1 with umbilical hernia, both moderate) and 1 subject 
in the CC-93538 360 mg group (severe appendicitis).  All SAEs in the DB Treatment Period were 
assessed as unrelated to study drug.  Six subjects experienced 1 SAE each in the OLE, of which 2 
had severe, possibly related events (cholecystitis acute and abortion spontaneous) and 4 had 
unrelated or unlikely related events (moderate asthma,
diverticulitis with perforation, 
schizophrenia, and femur fracture due to motorcycle accident).  Anti-drug antibodies were 
assessed and were not associated with any safety findings.  
Mean CC-93538 serum trough concentration (Ctrough) values for subjects in the 360 mg dose 
group were approximately 2-fold of mean CC-93538 Ctrough values for subjects in the 180 mg 
dose group at each visit, suggesting a dose-proportional increase in exposure. During the OLE, 
mean CC-93538 Ctrough values were similar across double-blind randomized treatment groups 
by OLE at Week 12, with these levels sustained through OLE at Week 52. CC-93538 trough 
concentration data showed steady state was reached between Weeks 12 and 16 of dosing, 
consistent with the t½.
These Phase 2 data indicate that targeting IL-13 with CC-93538 significantly improves many of 
the important disease and symptomatic features of EoE and is well tolerated. The data support the 
further study of CC-93538 as a novel treatment for EoE.
Refer to the Investigator’s Brochure for detailed information concerning the available 
pharmacology, toxicology, drug metabolism, clinical studies, and AE profile of the investigational 
product (IP).
1.3
Rationale
1.3.1
Study Rationale and Purpose
There is strong preclinical evidence for the role of IL-13 in the underlying pathophysiology of 
EoE.  Results of the CC-93538 Phase 2 EoE study indicate that targeting IL-13 with CC-93538 
significantly improved many of the important disease features of EoE and was well tolerated. In 
this study (RPC02-201) of 99 adult subjects with EoE, weekly administration of CC-93538 360 mg 
SC reduced mean esophageal eosinophil count and improved other inflammatory and symptomatic 
parameters. 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.  
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
39
1.3.1.1
Benefit-Risk Assessment
As few treatment options exist for patients with EoE, there is an unmet need for new 
pharmacotherapies targeting the pathophysiology of EoE with a safety and tolerability profile 
acceptable for long-term treatment.  Based on the clinical safety and efficacy data with CC-93538 
reported to date, including results from the completed Phase 2 EoE study, the benefit-risk 
assessment of CC-93538 supports further development in EoE and other inflammatory conditions.
The overall safety profile of CC-93538 remained consistent with the information that has been 
presented in the 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 interleukin-4 [IL-4] 
receptor), lebrikizumab (targeting IL-13), and tralokinumab (targeting IL-13) also have not been 
associated with an increased risk of serious viral infections. Although targeted coronavirus disease 
2019 (COVID-19) related research with these agents is limited, small studies conducted in patients 
with atopic dermatitis from high endemic areas (eg, Lombardy, Italy) provide 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 7.2.4 and Section 7.2.5), and criteria for reinitiating IP on resolution of 
a COVID-19 infection (Section 7.2.4). To facilitate reporting of COVID-19 events that occur 
during the study, all AEs and SAEs related to severe acute respiratory syndrome coronavirus 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 (eCRF) forms, which will allow the Sponsor to further evaluate these events.  
While the global coronavirus disease 2019 (COVID-19) pandemic has been identified as a 
potential risk to clinical trial subjects in general, and it may particularly affect individuals with 
underlying chronic diseases, the overall benefit-risk for participation in this EoE study with CC-
93538 is considered favorable.  The individual benefit-risk considerations regarding COVID-19 
infection remains the responsibility of the Investigator.  Testing to exclude COVID-19 infection 
prior to enrollment and to inform decisions about subject care during the study should follow local 
standard practice and requirements.
Non-live COVID-19 vaccination is allowed and will be 
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
40
documented as a concomitant medication within the study. The efficacy and safety of non-live 
vaccines (including non-live COVID-19 vaccines) in subjects receiving CC-93538 are unknown.
1.3.2
Rationale for the Study Design
The Phase 3 program includes a multicenter, multinational, randomized, double-blind, placebo-
controlled induction and maintenance study to evaluate the efficacy and safety of CC-93538 in 
adult and adolescent subjects with EoE (Study CC-93538-EE-001, the core Phase 3 study) with a 
separate, optional Open-Label Extension Study (OLE; Study CC-93538-EE-002).  The core Phase 
3 study will enroll both subjects who have had an inadequate response to or are intolerant to 
corticosteroid therapy (Steroid Inadequate Responders/Intolerant; approximately 70% of the study 
population) as well as subjects who are naïve or have had an adequate response to corticosteroid 
therapy (Steroid Responders/Naïve; approximately 30% of the study population).  The study 
includes a 24-week Induction Phase followed by a 24-week Maintenance Phase, for a total study 
duration of 48 weeks. A double-blind, placebo-controlled treat-through design with allowance for 
use of 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 
EoE.
An advisory panel of patients with EoE and their caregivers has been consulted and input has been 
sought on the protocol design and development of patient-facing materials and recruitment 
initiatives. A series of 3 advisory boards took place between March 2021 and March 2022. The 
feedback and insights from these members of the EoE community have been considered in the trial 
awareness and recruitment materials developed for the study. 
The Sponsor has ongoing 
partnerships with US-based and global Patient Advocacy Groups to deliver trial awareness 
initiatives for the study.
1.3.2.1
Justification of Co-Primary Endpoints
The selection of the co-primary clinical endpoint, the mean change in dysphagia days (DD), 
evaluated over the prior 14-day period using the dysphagia modified Daily Symptom Diary 
(mDSD), from baseline to Week 24, for Induction Phase Week 24 is based on qualitative patient 
interviews conducted in the validation study EVA-20655, Assessment of the Content Validity and 
Reproducibility of the Dysphagia Daily Symptom Diary (DSD) in Patients with Eosinophilic 
Esophagitis.  In Study EVA-20655, patients reported dysphagia as the hallmark symptom of EoE.  
The assessment of the number of DD over a 14-day period using the mDSD captures the symptoms 
of dysphagia most often described by patients in Study EVA-20655: trouble swallowing, food 
going down slowly, and food getting stuck in the throat.  This is aligned with the Food and Drug 
Administration’s (FDA’s) draft and final guidance for developing drugs for the treatment of EoE 
noting that clinical trials of new medications for EoE should evaluate the treatment effect on both 
signs/symptoms and inflammation associated with EoE (FDA, 2019; FDA, 2020).  Results of post 
hoc analyses of Phase 2 data indicate that change in DD is a responsive measure of dysphagia 
symptoms based on anchoring analyses using the Global Assessment of Disease Severity-Subject 
(GADS-S) and Global Impression of Change in EoE Symptoms (GIC-EoE) instruments.  Further, 
the post hoc analysis of mean change in DD from baseline showed a nominal significant difference 
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
41
in the 360 mg SC once weekly group compared to placebo.  The number of DD, a frequency 
measure of symptoms important to the patient, is associated with severity information, as it is 
highly correlated to the mDSD composite score which incorporates severity of symptoms into the 
score.  Therefore, assessment of DD, which captures the symptoms of dysphagia most relevant to 
patients, has been chosen as the co-primary clinical endpoint for the Phase 3 program.
For the co-primary histologic endpoint, eosinophilic histologic response is defined as a peak 
esophageal eosinophil count ≤ 6/hpf, across all available esophageal levels, at Week 24, as this is 
the threshold recommended in the draft and final FDA guidance for developing drugs for the 
treatment of EoE (FDA, 2019, FDA, 2020).  This threshold is also supported by the report of a 
retrospective cohort trial utilizing the University of North Carolina EoE Database (Wolf, 2015).  
The study generated receiver operator characteristic curves for symptom and endoscopic response 
at different eosinophil count cutpoints (eosinophils/hpf) on 199 patients.  The cutpoints examined 
were < 30 eosinophils/hpf, < 20 eosinophils/hpf, < 15 eosinophils/hpf, < 10 eosinophils/hpf, < 5 
eosinophils/hpf, < 3 eosinophils/hpf, ≤ 1 eosinophils/hpf, and 0 eosinophils/hpf.  Among patients 
achieving a similar cut-off of < 5 eosinophils/hpf, 90% had endoscopic response, 86% had clinical 
response, and 79% had both symptomatic and endoscopic response.  Finally, this threshold 
provides confirmation of significant histologic response as it surpasses the current eosinophil 
threshold required for the diagnosis of EoE, which is ≥ 15 eosinophils/hpf (Wolf, 2015). 
1.3.3
Rationale for Dose, Schedule, and Regimen Selection
Based on results from the Phase 2 Study RPC02-201, the CC-93538 360 mg SC once weekly dose 
was selected for Phase 3. In addition, this study is designed to test if induction of response at the 
360 mg SC once weekly dose level followed by continued treatment at a lower dose level through 
administration of a less frequent dosing regimen would provide a similar persistence of response.  
PK modeling demonstrated the average exposure for the 180 mg dose once weekly and the 360 
mg dose once every other week is very similar. The fluctuation between Cmax and Ctrough is 
larger in the 360 mg dose administered every other week compared to the 180 mg dose 
administered every week but this is not expected to result in any clinically relevant differences 
between the 2 regimens. Further, a dose higher than 360 mg SC once weekly is not expected to 
provide additional therapeutic benefit, as trough concentrations observed in the 360 mg SC once 
weekly dose during the DB Treatment Period in the Phase 2 study exceeded the estimated in vitro 
EC95 (95% of the maximal effective concentration) for IL-13 neutralization.  Data from Study 
RPC02-201 also provide support that the intravenous (IV) loading dose (10 mg/kg) is not required
to achieve optimal efficacy. Subjects in the placebo group from the DB Treatment Period who 
transitioned to the CC-93538 360 mg SC regimen without receiving the IV loading dose in the 
OLE showed improvement in dysphagia symptoms and comparable reduction in eosinophil count 
at Week 12 of the OLE as was observed at Week 16 of the DB Treatment Period for subjects 
treated with CC-93538 360 mg with the IV loading dose. These subjects also showed a mean 
Ctrough concentration (56.8 μg/mL) approximately 5-fold higher than the half maximal effective 
concentration (EC50; 10 μg/mL) at Week 2 of the OLE. Collectively, PK and efficacy data support 
the IV loading dose is not needed to achieve optimal efficacy. 
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
42
Therefore, because (1) the CC-93538 360 mg once weekly regimen has shown an effect on both 
histological and clinical endpoints in Study RPC02-201, (2) the CC-93538 180 mg once weekly 
regimen has shown a relevant histological but not clinical effect in the same study, and (3) the CC-
93538 360 mg once every other week regimen is not expected to achieve concentrations different 
than the 180 mg once weekly regimen, the 360 mg once weekly dose was selected for the Induction 
Phase and the 360 mg once weekly and 360 mg once every other week doses were selected for the 
Maintenance Phase.  
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, at the time of study initiation, there were no comparators available for 
subjects with EoE who have had an inadequate response or are intolerant to corticosteroid therapy.
1.3.5
Rationale for 
 Potential Predictive 
EoE is characterized by eosinophil-predominant inflammation and additional pathogenesis 
including esophageal tissue remodeling and over-expression of 
 
 that are 
thought to play a role in EoE disease pathogenesis, such as
 
 in esophageal 
 tissue as well as
assessment 
will be evaluated for potential diagnostic or prognostic importance.
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 Table 3 for the Maintenance Phase.
Table 1:
Study Objectives
Primary Objectives
The primary objectives of the study are:

To assess the efficacy of CC-93538 versus placebo in reducing dysphagia symptoms at 24 weeks

To assess the efficacy of CC-93538 versus placebo in reducing esophageal eosinophil counts at 24 weeks
Secondary Objectives
The secondary objectives are:

To assess the efficacy of CC-93538 versus placebo at 24 weeks in improving:

Endoscopic features of eosinophilic esophagitis (EoE) 

Histologic features of EoE

To assess the persistence of effect of CC-93538 at 48 weeks in reducing:

Dysphagia symptoms

Esophageal eosinophil counts

To assess the persistence of effect of CC-93538 through administration of a less frequent dosing regimen at 48 
weeks in reducing:

Dysphagia symptoms

Esophageal eosinophil counts
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
43
Table 1:
Study Objectives

To assess the persistence of effect of CC-93538 at 48 weeks in improving:

Endoscopic features of EoE 

Histologic features of EoE

To evaluate the time to and frequency of EoE flare events and use of rescue therapy during the study

To evaluate the safety and tolerability of CC-93538 including characterization of the immunogenicity profile

To assess trough concentrations of CC-93538 in subjects with EoE
Table 2:
Study Endpoints: Induction Phase Endpoints at Week 24
For endpoints listed below with statistical comparisons, the CC-93538 360 mg SC once weekly 
treatment arm (2 active arms combined) will be compared to the placebo arm.
Induction Phase Endpoints at Week 24
Endpoint
Name
Description
Timeframe
Co-primary 
Change in DD
Clinical Response
The mean change in dysphagia days (DD), evaluated 
over the prior 14-day period using the modified Daily 
Symptom Diary (mDSD), from baseline to Week 24
Week 24
Eosinophil 
Histologic Response 
(≤ 6/hpf)
The proportion of subjects with eosinophilic histologic 
response defined as a peak esophageal eosinophil count 
≤6/high-power field (hpf) at Week 24
Week 24
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
44
Table 2:
Study Endpoints: Induction Phase Endpoints at Week 24
For endpoints listed below with statistical comparisons, the CC-93538 360 mg SC once weekly 
treatment arm (2 active arms combined) will be compared to the placebo arm.
Induction Phase Endpoints at Week 24
Endpoint
Name
Description
Timeframe
Key 
Secondary
Eosinophil 
Histologic Response 
(< 15/hpf)
The proportion of subjects with eosinophilic histologic 
response defined as a peak esophageal eosinophil count 
< 15/hpf at Week 24
Week 24
EREFS 
The mean change in the endoscopic features of 
eosinophilic esophagitis (EoE) as measured by the EoE 
Endoscopic Reference Score (EREFS) from baseline to 
Week 24 
Week 24
EoEHSS Grade 
Score
The mean change in the mean adjusted histology grade 
score as measured by the EoE histology scoring system 
(EoEHSS) from baseline to Week 24
Week 24
EoEHSS Stage 
Score
The mean change in the mean adjusted histology stage 
score as measured by the EoE histology scoring system 
(EoEHSS) from baseline to Week 24
Week 24
mDSD Composite 
Score
The mean change in the modified Daily Symptom Diary 
(mDSD) composite score from baseline to Week 24
Week 24
Additional 
Secondary
DD Clinical 
Responder 
Definition
The proportion of subjects with a ≥ 50% decrease in 
dysphagia days (DD) from baseline at Week 24
Week 24
Kinetics and Onset 
of Clinical Response
The mean change in dysphagia days (DD) over time 
from baseline through Week 24
Through 
Week 24
Kinetics and Onset 
of Clinical Response
The mean change in the modified Daily Symptom Diary 
(mDSD) composite score over time from baseline 
through Week 24
Through 
Week 24
Time to Event
The time to event of EoE flare during the Induction 
Phase
Through 
Week 24
Time to Event
The time to event of use of rescue therapy during the 
Induction Phase
Through 
Week 24
Proportion of 
Subjects with Event
The proportion of subjects with an EoE flare during the 
Induction Phase
Through 
Week 24
Proportion of 
Subjects with Event
The proportion of subjects with use of rescue therapy 
during the Induction Phase
Through 
Week 24
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
Through 
Week 24
Pharmacokinetics
Measurements of trough concentrations of CC-93538 in 
subjects with EoE during the Induction Phase
Through 
Week 24
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
45
Table 2:
Study Endpoints: Induction Phase Endpoints at Week 24
For endpoints listed below with statistical comparisons, the CC-93538 360 mg SC once weekly 
treatment arm (2 active arms combined) will be compared to the placebo arm.
Induction Phase Endpoints at Week 24
Endpoint
Name
Description
Timeframe
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
46
Table 2:
Study Endpoints: Induction Phase Endpoints at Week 24
For endpoints listed below with statistical comparisons, the CC-93538 360 mg SC once weekly 
treatment arm (2 active arms combined) will be compared to the placebo arm.
Induction Phase Endpoints at Week 24
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
47
Table 3:
Study Endpoints:  Maintenance Phase Endpoints at Week 48
For endpoints listed below with statistical comparisons, the 2 CC-93538 dosing regimens (360 
mg SC once weekly and 360 mg SC once every other week) will be compared to placebo 
separately.
Maintenance Phase Endpoints at Week 48
Endpoint
Name
Description
Timeframe
Secondary
Change in DD 
Clinical Response
The mean change in dysphagia days (DD), evaluated over 
the prior 14-day period using the modified Daily 
Symptom Diary (mDSD), from baseline to Week 48
Week 48
Eosinophil 
Histologic 
Response (≤ 6/hpf)
The proportion of subjects with eosinophilic histologic 
response defined as a peak esophageal eosinophil count ≤ 
6/high-power field (hpf) at Week 48
Week 48
Eosinophil 
Histologic 
Response (< 15/hpf)
The proportion of subjects with eosinophilic histologic 
response defined as a peak esophageal eosinophil count < 
15/hpf at Week 48
Week 48
EREFS
The mean change in the endoscopic features of 
eosinophilic esophagitis (EoE) as measured by the EoE 
Endoscopic Reference Score (EREFS) from baseline to 
Week 48
Week 48
EoEHSS Grade 
Score
The mean change in the mean adjusted histology grade 
score as measured by the EoE histology scoring system 
(EoEHSS) from baseline to Week 48
Week 48
EoEHSS Stage 
Score
The mean change in the mean adjusted histology stage 
score as measured by the EoE histology scoring system 
(EoEHSS) from baseline to Week 48
Week 48
mDSD Composite 
Score
The mean change in the modified Daily Symptom Diary 
(mDSD) composite score from baseline to Week 48
Week 48
Eosinophil 
Histologic 
Response (≤ 6/hpf)
The proportion of subjects with eosinophilic histologic 
response defined as a peak esophageal eosinophil count ≤ 
6/high-power field (hpf) at Week 48 among subjects with 
eosinophilic histologic response defined as a peak 
esophageal eosinophil count ≤ 6/hpf at Week 24
Week 48
Time to Event
The time to event of EoE flare during the study 
(Induction and Maintenance Phases)
Through 
Week 48
Time to Event
The time to event of use of rescue therapy during the 
study (Induction and Maintenance Phases)
Through 
Week 48
Proportion of 
Subjects with Event
The proportion of subjects with an EoE flare during the 
study (Induction and Maintenance Phases)
Through 
Week 48
Proportion of 
Subjects with Event
The proportion of subjects with use of rescue therapy 
during the study (Induction and Maintenance Phases)
Through 
Week 48
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
48
Table 3:
Study Endpoints:  Maintenance Phase Endpoints at Week 48
For endpoints listed below with statistical comparisons, the 2 CC-93538 dosing regimens (360 
mg SC once weekly and 360 mg SC once every other week) will be compared to placebo 
separately.
Maintenance Phase Endpoints at Week 48
Endpoint
Name
Description
Timeframe
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 
Through 
Week 48
Pharmacokinetics
Measurements of trough concentrations of CC-93538 in 
subjects with EoE during the Maintenance Phase
Through 
Week 48 
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
49
Table 3:
Study Endpoints:  Maintenance Phase Endpoints at Week 48
For endpoints listed below with statistical comparisons, the 2 CC-93538 dosing regimens (360 
mg SC once weekly and 360 mg SC once every other week) will be compared to placebo 
separately.
Maintenance Phase Endpoints at Week 48
Endpoint
Name
Description
Timeframe
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
50
Table 3:
Study Endpoints:  Maintenance Phase Endpoints at Week 48
For endpoints listed below with statistical comparisons, the 2 CC-93538 dosing regimens (360 
mg SC once weekly and 360 mg SC once every other week) will be compared to placebo 
separately.
Maintenance Phase Endpoints at Week 48
Endpoint
Name
Description
Timeframe
3
OVERALL STUDY DESIGN
3.1
Study Design
The Phase 3 program includes a multicenter, multinational, randomized, double-blind, placebo-
controlled induction and maintenance study to evaluate the efficacy and safety of CC-93538 in 
adult and adolescent subjects with EoE (Study CC-93538-EE-001) with a separate, optional Open-
Label Extension Study (OLE; Study CC-93538-EE-002).  Globally, the study includes both 
subjects who have had an inadequate response to or are intolerant to corticosteroid therapy (Steroid 
Inadequate Responders/Intolerant; approximately 70% of the study population) as well as subjects 
who
are naïve or have had an adequate response to corticosteroid therapy (Steroid 
Responders/Naïve; approximately 30% of the study population).  However, in Germany, Spain, 
and the United Kingdom, only subjects who have had an inadequate response to corticosteroid 
therapy or are intolerant to corticosteroid therapy will be enrolled in the studies. Also, in Austria, 
Germany, Spain, and Switzerland, adolescent subjects will not be enrolled.  The study will include 
a 24-week Induction Phase followed by a 24-week Maintenance Phase.  Subjects will be 
randomized at the beginning of the study into 3 treatment arms: placebo for Induction and 
Maintenance, CC-93538 360 mg SC once weekly for Induction followed by 360 mg SC once every 
other week for Maintenance, or CC-93538 360 mg SC once weekly for Induction and 
Maintenance.  All subjects will receive CC-93538 360 mg SC once weekly in the optional OLE 
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
51
study; the dosing regimen may be revised through an amendment to the OLE study protocol once 
results from Study CC-93538-EE-001 are available and the most effective and safest dosing 
regimen is confirmed.  An overview of the study design is presented in Figure 1.
Figure 1:
Overall Study Schema
Abbreviations:  EGD = esophagogastroduodenoscopy; EoE = eosinophilic esophagitis; IP = investigational product;
N = sample size; OLE = Open-Label Extension; SC = subcutaneous injection
This study will empanel a steering committee (Section 9.9.5), and safety monitoring will be 
performed by an external, independent Data Monitoring Committee (Section 9.9.4) in addition to 
routine internal review by the Safety Management Team (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, but the 
EGD may not be performed during the last 2 weeks of screening when the mDSD will be evaluated 
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
52
for the baseline time point. All other screening procedures should be performed during the 4-week 
Screening Period prior to Day 1. Symptoms of EoE will be assessed with the mDSD, which will
be completed daily for at least the last 3 consecutive weeks (21 days) but may be completed for up 
to 28 days prior to Day 1.  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 399
subjects 12 to 75 years of age, inclusive, with a diagnosis of EoE and with symptoms of dysphagia 
will be randomized 1:1:1 (N ≈ 133 per treatment arm) to receive CC-93538 360 mg subcutaneously 
(SC) once weekly (2 of the 3 treatment arms) or matching placebo, in a double-blind fashion for 
24 weeks.  Subjects will be required to have symptoms of dysphagia of at least 4 DD as assessed 
with the mDSD over the prior 2 consecutive weeks (14 days) before baseline and histologic 
evidence of EoE defined as a peak count of ≥ 15 eosinophils per hpf at any 2 levels of the 
esophagus (proximal, mid, distal); both assessments will be conducted when not receiving anti-
inflammatory therapy. Peak esophageal eosinophil count will be confirmed by the central reader.  
Additionally, subject eligibility also includes a previous PPI trial without a complete response as 
described in Section 4.2, Inclusion Criterion 4.  Treatment assignment at baseline will be stratified 
based on steroid responder status 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.
Of the approximately 399 subjects to be enrolled, approximately 30 adolescent subjects will be 
included and approximately 70% will be Steroid Inadequate Responders/Intolerant (see
Section 7.3).  Subjects weighing ≥40 kg will be enrolled as this aligns with the eligibility criteria 
used in the Phase 2 program. 
Clinical laboratory tests, vital signs, physical examinations (including height and weight), 
pregnancy tests (female of childbearing potential [FCBP] subjects only), EGD, clinical symptom 
assessment, 
 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 24 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 6.4.2.8. For example, subjects with a severe EoE flare, as 
defined in Section 6.4.2.7, requiring endoscopic intervention and/or concomitant use of rescue 
therapy, including but not limited to corticosteroid therapy or dilation procedure, will not be 
eligible for participation in the Maintenance Phase.  A placebo-controlled Maintenance Phase will 
allow for a determination of persistence of treatment effect and the overall long-term efficacy of
CC-93538.
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
53
The Maintenance Phase treatment arms include 360 mg SC once every week, 360 mg SC once 
every other week, and matching placebo. As assigned upon randomization to the Induction Phase, 
approximately half of the subjects receiving CC-93538 360 mg SC once weekly during Induction 
will continue on the same dosing regimen for the Maintenance Phase and the remaining subjects 
will continue on the less frequent regimen of 360 mg SC once every other week.  Subjects 
originally randomized to placebo will remain on placebo.  
Clinical laboratory tests, vital signs, physical examinations (including height and weight), 
pregnancy tests (FCBP subjects only), EGD, clinical symptom assessment, 
 
 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:  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
Safety Follow-up Visits
Subjects who complete Week 48 of the Maintenance Phase and do not participate in the OLE study
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.  For subjects who discontinue the study prematurely 
for any reason, the Early Termination (ET) Visit will be conducted (Section 6.2.2).  In addition to 
the 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).  
3.1.5
Worsening of EoE Symptoms 
Subjects with a worsening of EoE symptoms during the study, either in the Induction Phase or 
Maintenance Phase will be required to complete the EoE Flare Assessment Visit per the Table of 
Events (Table 4 and Table 5).  For subjects with a worsening of EoE symptoms, an EGD will be 
required to determine if rescue therapy is clinically indicated.  Subjects with increased signs and 
symptoms of EoE are instructed to contact the Investigator and/or study staff to determine if an 
EoE Flare Assessment Visit is warranted.
Any worsening of EoE symptoms during study participation will be documented as an EoE flare.  
See Sections 6.4.2.7 and 6.2.1 for the protocol definition of EoE flare and EoE Flare Assessment
Visit details, respectively.
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
54
Subjects experiencing a severe EoE flare in the Induction or Maintenance Phase may continue to 
participate with concomitant rescue therapy as needed and will be eligible to enter the OLE study 
only following completion of Week 24 of the Induction Phase or Week 48 of the Maintenance
Phase, respectively (refer to Section 6.4.2.7 for details).  Subjects with a severe EoE flare in the 
Induction Phase will not qualify for entry into the Maintenance Phase.
Subjects experiencing a mild to moderate EoE flare in Induction will continue on into the 
Maintenance Phase of the study and will be eligible to enter the OLE study following the 
completion of the Week 48 Visit.
3.2
Study Duration for Subjects 
The maximum duration of subject participation in this study is approximately 72 weeks. Subjects 
will participate up to 4 weeks in the Screening Period (the screening EGD may be completed up 
to 8 weeks prior to Day 1), 24 weeks in the Induction Phase Treatment Period, and 24 weeks in 
the Maintenance Phase Treatment Period of the study.  Following Induction, subjects not entering 
the Maintenance Phase or OLE study will return for an Interim and a Final Safety Follow-up Visit 
at 8 and 16 weeks, respectively after final IP administration for the assessment of safety and 
clinical status. Similarly, subjects completing the Maintenance Phase who do not continue to 
participate in the OLE study will complete the Interim and the Final Safety Follow-up Visits (at 8 
and 16 weeks) after final IP administration; for these subjects, the maximum duration is 
approximately 71 weeks.  However, as an exception, the maximum duration of participation will 
be approximately 72 weeks for subjects permanently discontinuing IP during the Maintenance 
Phase but who continue study participation through Week 48, as the Interim and Final Safety 
Follow-up Visits will occur 8 and 16 weeks after the last study visit instead of the last dose of IP.
3.3
End of Study
The End of Study is defined as either the date of the last visit of the last subject to complete the 
post-treatment follow-up, or the date of receipt of the last data point from the last subject that is 
required for primary, secondary 
 analysis, as pre-specified in the protocol, 
whichever is the later date.
4
STUDY POPULATION
4.1
Number of Subjects 
Globally, the study population will consist of males and females aged 12 to 75 years (inclusive) 
with EoE who have had an inadequate response to corticosteroid therapy (as defined in Section 4.2, 
Inclusion Criterion 5a) or are intolerant to corticosteroid therapy (Steroid Inadequate 
Responders/Intolerant; approximately 70% of the study population) as well as subjects who are 
naïve or have had an adequate response to corticosteroid therapy (Steroid Responders/Naïve; 
approximately 30% of the study population).  A total of approximately 369 adults (aged 18 to 75 
years) and 30 adolescents (aged 12 to 17 years) will be enrolled in the study.
However, in Germany, Spain, and the United Kingdom, only subjects who have had an inadequate 
response to corticosteroid therapy or are intolerant to corticosteroid therapy will be enrolled in the 
study. In Austria, Germany, Spain, and Switzerland, adolescent subjects will not be enrolled.
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
55
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 ≥40 kg (88.2 lb) 
at the time of signing the informed consent form (ICF)/assent form.
Note:  Countries or sites with local restrictions that prohibit enrollment of adolescents (aged 
12 to 17 years inclusive) will only enroll subjects who are 18 years of age or older.  Enrollment 
of adolescent subjects will begin only after the applicable regulatory requirements for enrolling 
subjects in that age group have been satisfied and the necessary health authority approvals have 
been granted.  Where national or regional guidelines for the definition of adolescence differ 
from the definition stated above, the national or regional guidelines may be used to determine 
eligibility.
In Austria, Germany, Spain, and Switzerland, adolescent subjects will not be 
enrolled.
2) Subject has histologic evidence of EoE, defined as a peak count of ≥15 eosinophils per high-
power field (hpf) at any 2 levels of the esophagus (proximal, mid, and/or distal) when off anti-
inflammatory therapy (eg, corticosteroids, see Exclusion Criterion 7) for EoE. The histologic 
criterion for diagnosis of EoE must be confirmed by a centrally read histological assessment 
of an EGD specimen during the Screening Period prior to randomization.
3) Subject has symptoms of dysphagia of at least 4 DD, as assessed with the mDSD instrument,
over the last 2 consecutive weeks (14 days) prior to Day 1 when off anti-inflammatory therapy 
(eg, corticosteroids, see Exclusion Criterion 7) for EoE.  Subjects are required to have at least 
11 days of diary data out of the final 14-day period of screening mDSD collection in order to 
be enrolled in the study. During these 11 days, responses to questions 2 through 5 of the mDSD 
instrument must be complete. 
4) Subject must have previously received an adequate trial of proton-pump inhibitor (PPI) 
medication (8 weeks per guidance, Dellon, 2013) that did not provide complete response to 
EoE, or the subject remains symptomatic with continued use (Dellon, 2018b; Lucendo, 2017). 
Prospective subjects who discontinued use of a PPI must not have received a PPI for at least 
4 weeks before their first Screening Visit and must agree not to restart a PPI during the study. 
If a prospective subject is receiving a PPI medication at screening, he or she must have been 
receiving a stable dose for at least 4 weeks prior to the first Screening Visit and agree to 
continue the same dose throughout the study.
5) Subject must either (1) be naïve or have had an adequate response to corticosteroid therapy (ie, 
classified as Steroid Responders/Naïve) or (2) have had an inadequate response to 
corticosteroid therapy and is not considered to be a candidate for continued corticosteroid 
therapy, or is intolerant to corticosteroid therapy.  For subjects who have previously received 
systemic or swallowed topical corticosteroids for EoE, designation of the status of Steroid 
Inadequate Responders/Intolerant will include either of the following definitions.  Note that if 
any of the below criteria are met, a subject will be deemed Steroid Inadequate 
Responders/Intolerant (approximately 70% of the study population) and cannot be classified 
as Steroid Responders/Naïve (approximately 30% of the study population). 
a) Inadequate response to corticosteroid therapy (failed to respond or lost response) and not 
considered a candidate for continued corticosteroid therapy:  subjects who have had a trial 
of at least 6 weeks of swallowed topical corticosteroid treatment or 4 weeks of systemic 
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
56
corticosteroids at doses in accordance to published guidelines for the management of EoE 
(Lucendo, 2017), or a trial for the treatment duration specified in the prescribing 
information for approved products and judged by the treating physician as not achieving 
clinical improvement or having clinical improvement initially but lost response while on 
therapy.
b) Intolerant to corticosteroid therapy: subjects who initiated systemic or swallowed topical 
corticosteroid treatment but were unable to achieve treatment durations or dose levels due 
to intolerance because of side effects, including intolerance from use of corticosteroids for
conditions other than EoE, or subjects with underlying conditions in which corticosteroid 
use is not recommended or contraindicated.
Documentation of type of therapy, treatment duration, and outcome details will be collected when 
possible. 
In Germany, Spain, and the United Kingdom, only subjects who have had an inadequate response 
to corticosteroid therapy or are intolerant to corticosteroid therapy will be enrolled. 
6) Subjects must agree to maintain a stable diet (including any food elimination diet for the 
treatment of food allergy or EoE) 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.  
7) Subjects currently receiving inhaled corticosteroids, leukotriene receptor antagonists (eg, 
montelukast), or mast cell stabilizers (eg, cromolyn sodium) for indications other than EoE, 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.  If 
recently discontinued, the medication must have been discontinued at least 4 weeks prior to 
the first Screening Visit.
8) Female subjects of childbearing potential must agree to practice a highly effective method of 
contraception. 
Highly effective methods of contraception are those that alone or in 
combination result in a failure rate of a Pearl index of less than 1% per year when used 
consistently and correctly.
A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some 
point, and 2) has not undergone a hysterectomy or bilateral oophorectomy or bilateral 
salpingectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer 
therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had 
menses at any time in the preceding 24 consecutive months. A FCBP must:
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.
                                                       
* 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.
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
57
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 and would therefore not be an acceptable method of contraception for subjects 
enrolled in this region

progestogen-only hormonal contraception associated with inhibition of ovulation, 
which may be oral, injectable, or implantable
Note: progestogen-only hormonal contraception is not approved in Japan and would 
therefore not be an acceptable method of contraception for subjects enrolled in this 
region

placement of an intrauterine device (IUD)

placement of an intrauterine hormone-releasing system (IUS)

bilateral tubal ligation; or bilateral tubal occlusion (if an implantable device was 
recently placed, the subject must use an additional effective method of birth control 
until full occlusion has been confirmed and documented)    

vasectomized partner (vasectomized partner is a highly effective birth control method 
provided that the partner is the sole sexual partner of the FCBP and has received 
medical assessment of the surgical success)

sexual abstinence
9) Subject is willing to receive weekly SC injections throughout the study.
10) Subject must understand and voluntarily sign an ICF prior to any study-related 
assessments/procedures being conducted. For subjects less than 18 years of age, subject assent 
must be obtained, and parental/legal representative consent is required.
11) Subject is willing and able to adhere to the study visit schedule and other protocol 
requirements.
4.3
Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
1) Subject has clinical or endoscopic evidence of the presence of any other disease that may 
interfere with or affect the histologic, endoscopic, and clinical symptom endpoints for this 
study (eg, erosive esophagitis Los Angeles [LA] classification Grade B or above, Barrett's 
esophagus, esophageal lichen planus, upper gastrointestinal bleed, achalasia, inflammatory 
bowel disease, diagnosed eosinophilic gastroenteritis [clinical symptoms and/or EGD findings
and confirmatory eosinophilia in gastric and/or duodenal mucosa], or significant hiatal hernia 
[> 3 cm], etc.).
2) Subject demonstrates presence of esophageal varices.
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
58
3) Subject has a known active Helicobacter pylori infection and/or is currently being treated for
this condition.
4) Subject has evidence of a severe endoscopic structural abnormality in the esophagus (eg, 
high-grade stenosis where an 8- to 10-mm endoscope could not pass through the stricture 
without dilation at the time of the screening EGD).
5) Subject had esophageal dilation for symptom relief during the Screening Period or within 8 
weeks prior to the first Screening Visit, or esophageal dilation is anticipated to be performed 
within 48 weeks of dosing during the study.  
6) Subject demonstrates evidence of immunosuppression or is receiving systemic 
immunosuppressive or immunomodulating drugs (eg, anti-IL-13 antibodies [except IP in this 
study], IL-4 receptor alpha antagonist antibodies [eg, dupilumab], anti-IL-5 antibodies, anti-
IL-17 antibodies, anti-immunoglobulin E [IgE] antibodies, α4β7 integrin inhibitor antibodies,
or any other monoclonal antibody, methotrexate, cyclosporine, azathioprine, mercaptopurine, 
interferon alpha [IFNα], tumor necrosis factor alpha [TNFα] inhibitors, etc.) within 5 drug 
half-lives prior to the first Screening Visit.  Any use of these medications will be prohibited 
during the study.
7) Subject is currently receiving systemic or swallowed topical corticosteroid medication. 
Prospective subjects with EoE previously treated with a corticosteroid must not have received 
a systemic corticosteroid within 8 weeks or swallowed topical corticosteroid within 4 weeks 
of the first Screening Visit.  
8) 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.  
9) Subject is currently receiving a leukotriene receptor antagonist (eg, montelukast) or mast cell 
stabilizer (eg, cromolyn sodium) for the indication of EoE.  Subjects must not have received a 
leukotriene receptor antagonist or mast cell stabilizer for EoE within 4 weeks of the first 
Screening Visit.  Any use for the treatment of EoE during the study will be prohibited.
10) Subject is currently successfully treated for EoE with dietary modifications (eg, food 
elimination diet) and is able to fully adhere to the diet resulting in a complete response to EoE 
(ie, the subject does not meet the symptoms of dysphagia requirement of at least 4 DD and 
histologic criterion for diagnosis of EoE per Section 4.2, Inclusion Criteria 2 and 3).
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.
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 biologic 
impact of the vaccine is stabilized, as determined by discussion between the Investigator and 
the Clinical Trial Physician.
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
59
13) Subject has received a live attenuated vaccine within one month prior to the first Screening
Visit or anticipates the need to be vaccinated with a live attenuated vaccine during the course 
of the study.  Administration of any live 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 the Phase 2 Study, RPC02-201, or any Phase 1 clinical study.
15) 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, gastritis, colitis, celiac disease, Mendelian disorder associated with EoE, or 
cardiovascular condition, or neurologic or psychiatric illness that compromises the prospective 
subject's ability to accurately document symptoms of EoE).
16) 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 that are 
not clinically significant in total bilirubin associated with Gilbert’s syndrome may participate.
17) 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.
18) 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).
19) Subject had a previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection within 4 weeks prior to screening.  Symptoms must have completely resolved and 
based on Investigator assessment in consultation with the Clinical Trial Physician, there are no 
sequelae that would place the participant at a higher risk of receiving investigational treatment.
20) Subject has known hereditary fructose intolerance (HFI).
21) Subject is pregnant or lactating.
22) 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. In Japan, a known hypersensitivity to any ingredient in the IP is also 
exclusionary.
23) 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.
24) Subject has a history of alcohol or drug abuse within 5 years prior to initiation of screening.
25) Subject has any significant medical condition, laboratory abnormality, or psychiatric illness 
that would prevent the subject from participating in the study.
26) 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.
27) Subject has any condition that confounds the ability to interpret data from the study.
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
60
5
TABLE OF EVENTS
Table 4:
Table of Events for the Induction Phase
Study Procedures
Screeninga
Induction Phase Treatment Period
EoE 
Flare 
Visite
ET 
Visitf
Interim 
8-week
Safety 
Follow-
up Visitg
Final 16-
week 
Safety 
Follow-
up Visitg
Visit Label
Visit 
1b
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8c,d
Visit Week
(Window)
Day
-28 to -1
Day 1
Week 2
(Day 
15±3d)
Week 4
(Day 
29±3d)
Week 8
(Day 
57±3d)
Week 12
(Day 
85±3d)
Week 16
(Day 
113±3d)
Week 20
(Day 
141±3d)
Week 24
(Day 
169±3d)
Week 31
(Day 
218±7d)
Week 39
(Day 
274±7d)
Informed 
consent/assent
X
Inclusion/
exclusion criteria
X
X
Demographics/baseline 
characteristics
X
Medical history
X
Prior therapy
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 and 
chemistryh,i
X
X
X
X
X
X
X
X
X
X
X
X
Coagulation panel
X
Urinalysish
X
X
X
X
X
X
X
X
Testing for hepatitis B 
and C and HIV
X
TB assessment
X
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
61
Table 4:
Table of Events for the Induction Phase
Study Procedures
Screeninga
Induction Phase Treatment Period
EoE 
Flare 
Visite
ET 
Visitf
Interim 
8-week
Safety 
Follow-
up Visitg
Final 16-
week 
Safety 
Follow-
up Visitg
Visit Label
Visit 
1b
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8c,d
Visit Week
(Window)
Day
-28 to -1
Day 1
Week 2
(Day 
15±3d)
Week 4
(Day 
29±3d)
Week 8
(Day 
57±3d)
Week 12
(Day 
85±3d)
Week 16
(Day 
113±3d)
Week 20
(Day 
141±3d)
Week 24
(Day 
169±3d)
Week 31
(Day 
218±7d)
Week 39
(Day 
274±7d)
Pregnancy test (FCBP 
only)j
X
X
X
X
X
X
X
X
X
X
X
Physical examinationk
X
X
X
X
X
X
X
X
X
X
X
Height (cm)
X
X
X
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
Electrocardiogram 
(ECG)
X
Serum antibodies to 
CC-93538h
X
X
X
X
X
X
X
Serum CC-93538 PK 
assessmenth
X
X
X
X
X
X
X
X
X
X
SARS-CoV-2 
serologym
X
X
X
Phone call remindero
X
Xo
Xo
Xo
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
62
Table 4:
Table of Events for the Induction Phase
Study Procedures
Screeninga
Induction Phase Treatment Period
EoE 
Flare 
Visite
ET 
Visitf
Interim 
8-week
Safety 
Follow-
up Visitg
Final 16-
week 
Safety 
Follow-
up Visitg
Visit Label
Visit 
1b
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8c,d
Visit Week
(Window)
Day
-28 to -1
Day 1
Week 2
(Day 
15±3d)
Week 4
(Day 
29±3d)
Week 8
(Day 
57±3d)
Week 12
(Day 
85±3d)
Week 16
(Day 
113±3d)
Week 20
(Day 
141±3d)
Week 24
(Day 
169±3d)
Week 31
(Day 
218±7d)
Week 39
(Day 
274±7d)
Modified Daily 
Symptom Diary 
(mDSD)p
X
X
X
X
X
X
X
X
X
X
X
X
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
63
Table 4:
Table of Events for the Induction Phase
Study Procedures
Screeninga
Induction Phase Treatment Period
EoE 
Flare 
Visite
ET 
Visitf
Interim 
8-week
Safety 
Follow-
up Visitg
Final 16-
week 
Safety 
Follow-
up Visitg
Visit Label
Visit 
1b
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8c,d
Visit Week
(Window)
Day
-28 to -1
Day 1
Week 2
(Day 
15±3d)
Week 4
(Day 
29±3d)
Week 8
(Day 
57±3d)
Week 12
(Day 
85±3d)
Week 16
(Day 
113±3d)
Week 20
(Day 
141±3d)
Week 24
(Day 
169±3d)
Week 31
(Day 
218±7d)
Week 39
(Day 
274±7d)
EGD with tissue 
biopsiesr
X
X
Xs
Xt
EoE Endoscopic 
Reference Score 
(EREFS)
X
X
Xs
Xt
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
64
Table 4:
Table of Events for the Induction Phase
Study Procedures
Screeninga
Induction Phase Treatment Period
EoE 
Flare 
Visite
ET 
Visitf
Interim 
8-week
Safety 
Follow-
up Visitg
Final 16-
week 
Safety 
Follow-
up Visitg
Visit Label
Visit 
1b
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8c,d
Visit Week
(Window)
Day
-28 to -1
Day 1
Week 2
(Day 
15±3d)
Week 4
(Day 
29±3d)
Week 8
(Day 
57±3d)
Week 12
(Day 
85±3d)
Week 16
(Day 
113±3d)
Week 20
(Day 
141±3d)
Week 24
(Day 
169±3d)
Week 31
(Day 
218±7d)
Week 39
(Day 
274±7d)
Entry to Maintenance 
Phaseu
X
Randomization via 
IWRS
X
IP administrationv
X
X
X
X
X
X
X
Abbreviations: AE = adverse event; 
; d = day; ECG = electrocardiogram; 
 
 EGD = esophagogastroduodenoscopy; EoE = eosinophilic esophagitis; ePRO = electronic patient-reported outcome; 
 
EREFS = EoE Endoscopic Reference Score; ET = Early Termination; FCBP = female of childbearing potential; 
 
 HIV = human immunodeficiency virus; 
 IP = investigational product; 
IWRS = Interactive Web Response System; mDSD = modified Daily Symptom Diary; OLE = Open-Label Extension; 
 
 PK = pharmacokinetics; SAE = serious adverse event; SARS-
CoV-2 = severe acute respiratory syndrome coronavirus 2; 
; 
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 24) of the Induction Phase will also be the first visit in the Maintenance Phase.  See Table 5
for the Table of Events for the Maintenance 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 EoE Flare Assessment Visit should be scheduled as close as possible to the time that an EoE 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.
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
65
f Subjects who discontinue the study prior to completing the 24-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 EoE Flare Assessment Visit do not need to be repeated for subjects discontinuing the study prematurely due to an EoE flare.
g Subjects who complete the Induction Phase and do not enter either the Maintenance Phase or OLE study will be asked to complete the Interim 8-week Safety 
Follow-up Visit (8 weeks after final IP administration; at Week 31 for subjects that complete the Induction Phase) and the Final 16-week Safety Follow-up Visit 
(16 weeks after final IP administration; at Week 39 for subjects that 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 
Week 31 and 39).  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 24 or the ET Visit).
h Pre-dose collection, except for Safety Follow-up Visits (if applicable), the ET Visit (if applicable), and the EoE Flare Assessment Visit (if applicable; unless 
dose is taken that day).  
i
Fasting Lipid Panel and fasting glucose (instead of random glucose) will only be conducted at Day 1, Week 24, and the ET Visit (if applicable).
j
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. Additional pregnancy tests 
may be required per local guidelines. 
k Complete physical examination will be conducted at screening, Day 1, Week 24, both Safety Follow-up Visits (if applicable), and at the ET Visit (if applicable). 
Abbreviated physical examination will be conducted at Weeks 4, 8, 12, 16, and 20.
m Serum will be collected at Day 1 (baseline), Week 24, and the ET Visit (if applicable) as well as approximately 4 weeks after a documented or suspected SARS-
CoV-2 infection, for possible measurements of 
 per national and local requirements 
.
o A phone call will be made to subjects as a reminder to complete the mDSD.  The Table of Events X’s are noted in the visit before the start of the collection 
period in order to alert sites to the upcoming interim visit activity.  Phone calls will take place just prior to the beginning of the final 14-day mDSD data collection 
period for screening (just prior to Day -14) and for the Week 24 (just prior to Week 22) endpoint analyses.  For subjects who are required to complete the Safety 
Follow-up Visits, a phone call will take place before the 14-day mDSD data collection period just prior to the Interim Safety Follow-up Visit and the Final Safety 
Follow-up Visit, if applicable. During this call, subjects will also be reminded to complete the 
 at Day -14.
p The mDSD will be completed daily after the last meal of the day for at least the last 3 consecutive weeks (at least 21 days [up to 28 days]) during the Screening 
Period and daily from Day 1 through Week 24 using an electronic diary (eDiary) on a handheld device (ePRO instrument).  For subjects who are required to 
complete the Safety Follow-up Visits, the mDSD will also be completed daily for the 14-day period before each of the 2 Safety Follow-up Visits.  The ePRO 
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
66
instrument will be distributed to subjects at the Screening Visit. Subjects are instructed to continue daily completion of the mDSD in the time interval between 
the transition from Induction Phase to Maintenance Phase or Study CC-93538-EE-001 to the OLE Study, CC-93538-EE-002.
q The screening 
 will be conducted at Day -14.
r Esophagogastroduodenoscopy (EGD) biopsies will be measured for relevant 
 when possible.  The screening EGD must be completed within 8 
weeks prior to Day 1 but should not be performed during the last 2 weeks of screening just prior to Day 1.
s EGD is required at EoE 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 EoE flare, data should be collected for the EoE 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.
t
EGD is not required at Early Termination Visits that occur before Week 8 of the study.
u The Investigator will confirm the subject’s suitability for entry to the Maintenance Phase according to protocol requirements detailed in Section 6.4.2.8.
v Once weekly IP administration (CC-93538 or placebo: subcutaneous [SC] doses on Day 1 followed by SC doses weekly from Week 1 through Week 23 [ie, a 
total of 24 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.
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
67
Table 5:
Table of Events for the Maintenance Phase
Study Procedures
Maintenance Phase Treatment Period
EoE 
Flare 
Visitb
ET 
Visitc
Interim 
8-week 
Safety 
Follow-
up 
Visitd
Final 16-
week 
Safety 
Follow-
up Visitd
Visit Label
Visit 
8a
Visit 
9
Visit 
10
Visit 
11
Visit 
12
Visit 
13
Visit 
14
Visit Week 
(Window)
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±5d)
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
AEs/SAEs
X
X
X
X
X
X
X
X
X
X
X
Hematologye
X
X
X
X
X
X
X
X
X
X
X
Chemistrye,f
X
X
X
X
X
X
X
X
Urinalysise
X
X
X
X
X
X
Urine pregnancy test 
(FCBP only)g
X
X
X
X
X
X
X
X
X
X
Physical 
examinationh
X
X
X
X
X
X
Height (cm)
X
X
X
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
Serum antibodies to 
CC-93538e
X
X
X
X
X
X
X
Serum CC-93538 
PK assessmente
X
X
X
X
X
X
X
X
X
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
68
Table 5:
Table of Events for the Maintenance Phase
Study Procedures
Maintenance Phase Treatment Period
EoE 
Flare 
Visitb
ET 
Visitc
Interim 
8-week 
Safety 
Follow-
up 
Visitd
Final 16-
week 
Safety 
Follow-
up Visitd
Visit Label
Visit 
8a
Visit 
9
Visit 
10
Visit 
11
Visit 
12
Visit 
13
Visit 
14
Visit Week 
(Window)
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±5d)
Week 55
(Day 
386±7d)
Week 63
(Day 
442±7d)
SARS-CoV-2 
serologyj
X
X
X
Phone call reminderk
Xk
Xk
Xk
Modified Daily 
Symptom Diary 
(mDSD)l
X
X
X
X
X
X
X
X
X
X
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
69
Table 5:
Table of Events for the Maintenance Phase
Study Procedures
Maintenance Phase Treatment Period
EoE 
Flare 
Visitb
ET 
Visitc
Interim 
8-week 
Safety 
Follow-
up 
Visitd
Final 16-
week 
Safety 
Follow-
up Visitd
Visit Label
Visit 
8a
Visit 
9
Visit 
10
Visit 
11
Visit 
12
Visit 
13
Visit 
14
Visit Week 
(Window)
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±5d)
Week 55
(Day 
386±7d)
Week 63
(Day 
442±7d)
EGD with tissue 
biopsiesm
X
X
Xn
Xo
1.0
Approved
930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
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Table 5:
Table of Events for the Maintenance Phase
Study Procedures
Maintenance Phase Treatment Period
EoE 
Flare 
Visitb
ET 
Visitc
Interim 
8-week 
Safety 
Follow-
up 
Visitd
Final 16-
week 
Safety 
Follow-
up Visitd
Visit Label
Visit 
8a
Visit 
9
Visit 
10
Visit 
11
Visit 
12
Visit 
13
Visit 
14
Visit Week 
(Window)
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±5d)
Week 55
(Day 
386±7d)
Week 63
(Day 
442±7d)
EoE Endoscopic 
Reference Score 
(EREFS)
X
X
Xn
Xo
IP administrationp
X
X
X
X
X
X
Abbreviations: AE = adverse event; 
 EGD = 
esophagogastroduodenoscopy; EoE = eosinophilic esophagitis; ePRO = electronic patient-reported outcome; 
 
 EREFS = EoE Endoscopic Reference Score; ET = Early Termination; FCBP = female of childbearing potential;  
 
 IP = investigational product; mDSD = modified Daily Symptom Diary; OLE = Open-
Label Extension; 
 
PK = pharmacokinetics; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; 
 
 
a The assessments performed at the Induction Phase Week 24 Visit will also serve as the data for the first visit of the Maintenance Phase (Maintenance Phase 
Week 24 is equivalent to Induction Phase Week 24) 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 24 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.
b An EoE Flare Assessment Visit should be scheduled as close as possible to the time that an EoE 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.
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Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
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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 EoE Flare Assessment Visit do not need to be repeated for subjects who are discontinuing the study prematurely due 
to an EoE flare.
d Subjects who complete the Maintenance Phase and do not enter the OLE study will be asked to complete the Interim 8-week Safety Follow-up Visit (8 weeks 
after final IP administration; at Week 55 for subjects that complete the Maintenance Phase) and the Final 16-week Safety Follow-up Visit (16 weeks following 
final IP administration; at Week 63 for subjects that 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 Safety Follow-up Visits (if applicable), the ET Visit (if applicable), and the EoE Flare Visit (if applicable; unless a dose is taken 
that day). 
f Fasting Lipid Panel and fasting glucose (instead of random glucose) will only be conducted at Week 24, 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. Additional pregnancy test may be required per local guidelines. 
h Complete physical examination to be performed at Maintenance Phase Week 24, Week 48, both Safety Follow-up Visits (if applicable) and at the ET Visit (if 
applicable).  Abbreviated physical examination to be conducted at Week 36.
j
Serum will be collected at Week 24, Week 48 and the ET Visit (if applicable) as well as approximately 4 weeks after a documented or suspected SARS-CoV-2 
infection, for possible measurements of 
 per national and local requirements 
k A phone call will be made to subjects as a reminder to complete the mDSD.  The Table of Events X’s are noted in the visit before the start of the collection 
period in order to alert sites to the upcoming interim visit activity.  Phone calls will take place just prior to the beginning of the 14-day mDSD data collection 
period for the Week 48 (just prior to Week 46) endpoint analysis.  For subjects who are required to complete the Safety Follow-up Visits, a phone call will take 
place before the 14-day mDSD data collection period just prior to the Interim Safety Follow-up Visit and the Final Safety Follow-up Visit, if applicable. 
l
The mDSD will be completed daily after the last meal of the day from Week 24 through Week 48 using an electronic diary (eDiary) on a handheld device (ePRO 
instrument).  For subjects who are required to complete the Safety Follow-up Visits, the mDSD will also be completed daily for the 14-day period before each 
of the 2 Safety Follow-up Visits. Subjects are instructed to continue daily completion of the mDSD in the time interval between the transition from Induction 
Phase to Maintenance Phase or Study CC-93538-EE-001 to the OLE Study, CC-93538-EE-002.
m Esophagogastroduodenoscopy (EGD) biopsies will be measured for relevant 
 when possible.  
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Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
72
n EGD is required at EoE 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 EoE flare, data should be collected for the EoE 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.
o EGD is not required at Early Termination Visits that occur before Week 32 of the Maintenance Phase.
p 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 24 
Induction Visit for most subjects). Subjects will then receive weekly doses through Week 47 (ie, a total of 24 doses of IP). Additionally, the Investigator will 
review the importance of IP compliance and evaluate compliance for each subject in accordance with the protocol.
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CC-93538-EE-001 Amendment 1.0
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6
PROCEDURES
Assessments and procedures for the Screening Period and the Induction Phase Treatment Period 
are outlined in Table 4.  Assessments and procedures for the Maintenance Phase Treatment Period 
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. 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 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): 

EoE clinical symptom assessment instruments

Spontaneous or solicited AE reporting

Vital signs

Physical examination

Clinical laboratory tests, including blood sampling for the assessment of serum CC-93538
levels, anti-drug antibodies (ADAs),

Esophagogastroduodenoscopy (EGD) (if applicable)

IP administration
Throughout the study, IP administration should occur on the same day each week.  For 
administration on study visit days, dosing should occur in the clinic.  In the event a study visit can 
only be scheduled on a different day of the week than the usual dosing day, subjects should 
maintain their usual dosing schedule when possible.  
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 mDSD will be evaluated for the baseline 
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Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
74
time point.  In addition, a preliminary assessment of inclusion/exclusion criteria, including the 
frequency of dysphagia 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 labs, 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 electronic patient-reported outcome (ePRO)
instruments including the electronic diary (eDiary [the mDSD]) on a handheld device will be 
distributed to subjects at the Screening Visit.
After completion of a training module, the mDSD will be completed daily for at least the last 3 
consecutive weeks (21 days) during the Screening Period (prior to Day 1) but may be collected for 
up to 28 consecutive days during screening.  Subjects are required to have completed at least 11 
days of mDSD data collection out of the final 14 days of screening (ie, the final 14-day period 
preceding Day 1) in order to be enrolled in the study.  A phone call will be made to subjects as a 
reminder to complete the mDSD.  Phone calls will take place just prior to the beginning of the 
final 14-day mDSD data collection period for screening (prior to Day -14) which serves as the 
study baseline.  The mDSD will be completed daily during the Induction and Maintenance Phases, 
and for those subjects who are required to complete the Safety Follow-up Visits (Section 6.3.1), 
the mDSD will be completed daily for the 14-day period before each of the 2 Safety Follow-up 
Visits.  During the study, additional phone call reminders will take place before the 14-day 
collection period preceding the Week 24 and Week 48 endpoint assessment (ie, just prior to Weeks 
22 and 46), before the collection period preceding the 2 Safety Follow-up Visits, if applicable, and 
a phone contact may be made at other time points as part of ongoing surveillance.
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, after 
informed consent/assent has been obtained:

Assessment of inclusion/exclusion criteria

Demographics and baseline characteristics

Medical history including atopy status (documentation of atopic conditions and 
pharmacotherapy) and details of any prior dilation procedures
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Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
75

Prior therapy and concomitant therapy including details of the determination of steroid 
responder status.  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 serious AEs (SAEs).  Once subjects consent, AEs/SAEs will be recorded at each study visit.  
Refer to Section 10 for definitions of AEs/SAEs, monitoring, and reporting.  In addition, 
device (ie, pre-filled syringe) 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 hemoglobin 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 24, Week 48, and the ET Visit (if applicable) 

Coagulation:  Prothrombin time (PT), activated partial thromboplastin time (aPTT), and 
international normalized ratio (INR)

Urinalysis:  leukocytes, specific gravity, bilirubin, blood, glucose, ketones, pH, protein, 
and urobilinogen

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 and ET 
Visit, if applicable) at screening and the additional time points outlined in the Table of 
Events (Table 4 and Table 5).

Testing for hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV (central laboratory) will 
be performed at screening only.

HBV:  Hepatitis B surface antigen (HBsAg) screening test and hepatitis B core antibody 
(HBcAb) test will be performed.  Subjects who test positive for HBsAg will be excluded 
from the study.  For subjects who test positive only for HBcAb, an HBV deoxyribonucleic 
acid (DNA) test must be performed.  If the HBV DNA test is positive, the subject will be 
excluded from the study.  If the HBV DNA test is negative (without antiviral therapy) and 
ALT and AST are ≤ ULN, the subject will be eligible for this study.

HCV:  HCV antibody (anti-HCV IgG) test will be performed.  Subjects testing positive for 
HCV antibody and have a positive confirmatory test (HCV ribonucleic acid [RNA]) will 
be excluded from the study.  Subjects with evidence of cleared HCV infection (eg, HCV 
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
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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 (enzyme-
linked immunosorbent assay [ELISA] test result, confirmed by western blot) will be 
excluded from the study.

Testing for tuberculosis (TB) will be performed at screening only.  Active TB must be ruled 
out according to local medical practices.  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 and Table 5).  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 and Table 5).

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 
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.

Modified Daily Symptom Diary (mDSD) (Section 6.4.2.1)

Phone call reminder for mDSD completion (just prior to Day -14)

EGD with tissue biopsies (Section 6.4.1)

EoE Endoscopic Reference Score (EREFS) (Section 6.4.1)
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Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
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6.1.1
Additional Information Regarding Safety Laboratory Assessments
Analysis of samples will be conducted by a central laboratory.  Details regarding collection of 
samples, shipment of samples, reporting of results, laboratory reference ranges, and alerting 
abnormal values will be supplied to the site before site initiation in a Study Laboratory Manual. 
The results of the analysis will be made available to each site by the central laboratory. 
Additional and repeat laboratory safety testing may be performed locally at the discretion of the 
Investigator.  As local laboratory data will not be collected in the electronic case report form 
(eCRF), if feasible, a sample should also be sent to the central laboratory.
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.
6.1.2.1
Rescreening of Subjects Who Develop COVID-19 During the Screening 
Period
Although molecular testing for asymptomatic COVID-19 infection is not required in this study, 
some subjects may develop suspected or confirmed symptomatic COVID-19 infection, or it is 
discovered that subjects have asymptomatic COVID-19 infection during the Screening Period.  In 
such cases, subjects may be considered eligible for the study after meeting all Inclusion/Exclusion 
Criteria related to active infection, and after meeting the following criteria:

At least 10 days (20 days for severe/critical illness) have passed since symptoms first appeared 
or positive test result, and

At least 24 hours have passed since last fever without the use of fever-reducing medications, 
and

Symptoms (eg, cough and shortness of breath) have resolved and

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 or regional 
guidelines
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CC-93538-EE-001 Amendment 1.0
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6.2
Induction Phase and Maintenance Phase Treatment Period
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 females of childbearing potential 
on Day 1 and the results reviewed prior to randomization.  A negative pregnancy test result 
must be obtained prior to randomization.  If the urine pregnancy test result is positive but this 
is believed to be a false positive, the site 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.
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 the Maintenance Phase, the assessments performed at the Week 24 Visit (Visit 8) of the 
Induction Phase will also serve as the data for the Maintenance Phase Week 24 Visit (Visit 8) and 
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930207646
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
79
do not need to be repeated specifically for the Maintenance Phase.  If the Maintenance Phase Week 
24 Visit, the first day of the Maintenance Phase, does not occur at the Induction Phase Week 24 
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 6.4.2.8.  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 is available if needed.  
If subjects are out of window for their Week 24 dose due to use of the additional +4 day window 
for the EGD, subjects should skip the Week 24 dose and take the Week 25 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:

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

Height and weight

Vital signs

Serum antibodies to CC-93538

Serum CC-93538 PK assessment

Modified Daily Symptom Diary (mDSD)

Phone call reminder for mDSD completion (just prior to Week 22 and Week 46)
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Approved
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
80

EGD with tissue biopsies

EoE Endoscopic Reference Score (EREFS)

Entry to the Maintenance Phase assessment (only at Induction Phase Week 24)

IP administration
Refer to Section 6.4 for a description of the efficacy assessments conducted throughout the study.
6.2.1
EoE Flare Assessment Visit
Subjects with a worsening of EoE symptoms during the study, either in the Induction Phase or 
Maintenance Phase will be required to complete the EoE Flare Assessment Visit as shown in the 
Table of Events (Table 4 and Table 5).  Subjects with increased signs and symptoms of EoE are 
instructed to contact the Investigator and/or study staff to determine if an EoE Flare Assessment 
Visit is warranted.  An EoE Flare Assessment Visit should be scheduled as close as possible to the 
time that an EoE flare is suspected.
Any worsening of EoE symptoms during study participation will be documented as an EoE flare.  
See Section 6.4.2.7 for the protocol definition of EoE flare and EoE Flare Assessment Visit details.
In the event that subjects discontinue the study prematurely due to an EoE flare, the ET Visit will 
also be completed, but procedures performed at the EoE Flare Assessment Visit do not need to be 
repeated for the ET Visit. 
If subjects had an EGD performed for an EoE flare assessment during the Induction (prior to Week 
24) or Maintenance (prior to Week 48) Phases, an EGD will also be performed at Week 24 or 48,
respectively.  However, an exception will be made if in the Investigator’s judgement the EoE flare 
assessment occurred too close to Week 24 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 24 or Week 48 Visit.
The following evaluations will be performed as specified in Table 4 and Table 5:

Concomitant therapy

Assessment of AEs/SAEs

Hematology, chemistry, and urinalysis*

Weight

Vital signs
                                                       
* Note that these samples do not need to be a pre-dose draw unless the subject is expected to dose later that day.
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Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
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
EGD with tissue biopsies**

EoE Endoscopic Reference Score (EREFS)**
Refer to Section 6.4 for a description of the efficacy assessments conducted throughout the study.
6.2.2
End of Treatment/ Early Termination (ET) Visit
For subjects who discontinue the study prematurely for any reason (ie, subjects that do not 
complete Week 48), every attempt should be made to complete the assessments detailed in the ET 
Visit conducted as close as possible to the time of study discontinuation.  If study discontinuation 
occurs at the regularly scheduled visit (eg, Induction Phase Week 12 or Maintenance Phase Week 
36), the ET Visit and all corresponding ET Visit procedures should be conducted (Table 4 and 
Table 5).  In addition, these subjects should return for the Safety Follow-up Visit (Section 6.3.1).  
Subjects who complete the Induction Phase Week 24 Visit but do not continue in the Maintenance 
Phase or OLE study should complete the Week 24/ET Visit and return for the Interim 8-week and
Final 16-week Safety Follow-up Visits at Week 31 and Week 39, respectively (Section 6.3.1).  
Subjects who complete the Induction Phase and enter the OLE study should complete the Week 
24/ET Visit; these subjects do not need to return for the 2 Safety Follow-up Visits.  Assessments 
conducted at the Week 24 Visit do not need to be repeated.  Subjects who complete the 
Maintenance Phase Week 48 but do not continue in the OLE study 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 EoE flare, ET procedures 
performed at the EoE 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

Height and weight
                                                       
** Note that EGD is required at EoE 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 EoE flare, medical record source data should be collected for the EoE 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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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
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
Vital signs

Serum antibodies to CC-93538

Serum CC-93538 PK assessment

Modified Daily Symptom Diary (mDSD)

EGD with tissue biopsies*

EoE Endoscopic Reference Score (EREFS)*
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 Visits (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 24, or 
subjects who complete Week 24 and do not enter the Maintenance Phase or the OLE study will 
return for an Interim and a Final Safety Follow-up Visit at 8 and 16 weeks, respectively after final 
IP administration (at Week 31 and Week 39 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 24 or the ET Visit).  
Assessments should be performed in accordance with the Table of Events (Table 4). Subjects who 
                                                       
Note that EGD is not required for ET Visits occurring before Week 8 in the Induction Phase or before Week 32 in 
the Maintenance Phase.
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Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
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continue participation in the Maintenance Phase or OLE study 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
or complete Week 48 but do not enroll in the OLE study 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 study will not 
return for the 2 Safety Follow-up Visits.
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

Weight

Vital signs

Serum antibodies to CC-93538

Serum CC-93538 PK assessment

Modified Daily Symptom Diary (mDSD) only for the 14-day period preceding each of the 2
Safety Follow-up Visits

Phone call reminder for mDSD completion just prior to the 14-day collection period preceding 
each of the 2 Safety Follow-up Visits 
6.4
Efficacy Assessment
6.4.1
Esophagogastroduodenoscopy (EGD)
To ensure quality data and standardization, the same person should perform endoscopic procedures 
at a study site at each study visit. 
The EGD biopsy results for eosinophil counts will be read 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 eosinophil counts will be blinded to 
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Approved
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
84
investigative sites.  After randomization, a local histologic assessment of EGD biopsy samples 
should not be performed, unless required for safety reasons (eg, severe EoE flare, AEs, or 
incidental findings, etc.).  Any incidental findings of potential clinical relevance that are not 
directly associated with the objectives of the study should be evaluated and handled by the 
Investigator per the site’s standard of care and clinical judgement.  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 and Table 
5).

Biopsies should be obtained from 3 levels, the proximal, mid, and distal esophagus, to 
maximize the likelihood of meeting histologic eligibility criteria for this study as follows:

Distal esophagus (3 to 5 cm above the Z-line [squamo-columnar junction])

Proximal esophagus (≈ 15 cm above the Z-line and within 10 cm of the esophageal inlet)

Mid esophagus (dependent on subject anatomy as described in the Study Laboratory 
Manual)

All subsequent biopsies should be obtained from the same levels as the screening biopsies (ie, 
all 3 levels) maintaining consistency throughout the study.

Biopsy samples must be obtained from 2 to 4 separate areas at each level, ideally from the 
areas with the most prominent visible abnormalities.  For example, if 2-bite biopsies are being 
obtained, a minimum total of 4 biopsy fragments (from 2 separate 2-bite biopsies) would be 
obtained from each esophageal level.

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 
EoE 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 14 days of the screening mDSD is collected.

Histologic analysis of the esophageal biopsy samples for any study-specific assessments will 
be performed by a central laboratory including enumeration of eosinophil count (peak 
eosinophil count) by analysis of hematoxylin and eosin (H&E) stained biopsies and EoE 
histology scoring system (EoEHSS) assessment (histology grade and stage score).

Endoscopic findings will be assessed by each Investigator using the EoE EREFS (Hirano, 
2013) in 5 classification categories at the time points specified in the Table of Events (Table 4
and Table 5).  The classification features include edema, fixed rings, exudates, furrows, and 
stricture.  Assessments will be conducted at all 3 levels of the esophagus (the proximal, mid, 
and distal).

In addition to obtaining the eosinophil counts required for inclusion in the study and primary 
endpoint determination, the esophageal biopsies will be used for evaluation of potential 
diagnostic 
 using appropriate laboratory methodology, 
including histopathology, immunohistochemistry, and transcript profiling.
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Approved
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
85
6.4.2
Clinical Symptoms of EoE
6.4.2.1
Modified Daily Symptom Diary (mDSD)
The mDSD is a patient-reported diary to assess the daily experience of dysphagia symptoms 
(APPENDIX B).  The original 4-item version of the DSD utilized in Phase 2 was modified to 
reflect the findings from the concept elicitation and cognitive interviews conducted with 
adolescent and adult EoE subjects in the mDSD validation study, EVA-20655.  The mDSD 
includes 6 primary questions and 2 sub-questions, including an assessment of solid food 
consumption that day (item 1), experience with trouble swallowing (item 2), food going down 
slowly (item 3), food getting stuck in the throat or chest (item 4), actions taken by subjects to 
obtain relief (item 5), and any pain associated with swallowing (item 6).  The recall period is 
“today,” as the diary is meant to be completed daily. 
The mDSD questions 2, 3, and 4 represent the primary symptoms to determine if a subject is 
experiencing dysphagia on any given day.  Specifically, a DD is defined as a “yes” response to 
any or all of mDSD questions 2, 3, and 4.  The mDSD composite score utilizes participant 
responses to mDSD questions 2, 3, 4, and 5.  Subjects will receive a single score of “1” for any or 
all “yes” response(s) to questions 2, 3, or 4 in order to capture an episode of dysphasia experienced 
during the day and will receive a score of 0 to 4 for the response to question 5 depending on the 
action taken to seek relief for the dysphagia episode.  Scores range from 0 to 70, with higher scores 
indicating more frequent and/or severe dysphagia. 
Subjects will complete the mDSD daily via an eDiary on a handheld device for at least the last 3 
consecutive weeks during the Screening Period.  Subjects are required to have completed at least 
11 days of mDSD data collection out of the final 14 days of screening (ie, the final 14-day period 
preceding Day 1) in order to be enrolled in the study.  A number of measures will be employed in 
order to enhance subject adherence to eDairy completion and limit the amount of missing data, 
which is critical to ensure interpretability of mDSD assessment in this study.  First, eDiary 
reminder alarms will allow subjects to select the timing for their alarm within a standardized 
window every evening such that completion occurs after the subject’s last meal of the day.  Second, 
ongoing surveillance of diary completion data will occur in order to correct any issues as close to 
real time as possible.  Third, subjects will receive reminder calls from site staff in advance of the 
14-day collection period preceding the screening (baseline) assessment and the Week 24 and 48 
assessments (as well as additional times as needed based on ongoing surveillance) to help ensure 
compliance with the daily diary completion requirements at critical assessment points during the 
study.  In addition, for subjects who are required to complete the Safety Follow-up Visits 
(Section 6.3.1), a phone contact will be made ahead of the 14-day period before each of the 2 
Safety Follow-up Visits.
The mDSD will be administered daily in the evening or at bedtime after the subject’s last meal of 
the day via an eDiary for at least the last 3 consecutive weeks (at least 21 days, but up to 28 days) 
in screening, 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 for the 14-day period just prior to 
each of the 2 Safety Follow-up Visits (if applicable) according to the Table of Events (Table 4 and 
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
86
Table 5).  Subjects are instructed to continue daily completion of the mDSD in the time interval 
between the transition from Induction Phase to Maintenance Phase or Study CC-93538-EE-001 to 
the OLE study.
Further assessment of the psychometric properties of the mDSD in a Phase 3 study will include a 
preliminary blinded analysis after the first one-third of subjects complete 24 weeks of treatment in 
the Induction Phase as well as a final analysis, in all subjects completing Week 24, at the end of 
the study.  These analyses will focus on the reproducibility, validity, and responsiveness of the DD 
and mDSD composite score endpoints as well as confirmation of the clinically meaningful 
response definition for the clinical co-primary endpoint, mean change in DD from baseline to 
Week 24, as described in a separate Psychometric Analysis Plan.  The reproducibility of the mDSD 
will be assessed among “stable” subjects (ie, those reporting no change in 
 rating at Week 
2) using 2 consecutive 14-day periods, the final 14-days of screening (baseline) and Weeks 1 to 2.  
1.0
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6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
87
6.4.2.7
Worsening of EoE Symptoms, EoE Flare, and the EoE Flare 
Assessment Visit
Subjects with a worsening of EoE symptoms during the study, either in the Induction Phase or 
Maintenance Phase will be required to complete the EoE Flare Assessment Visit as shown in the 
Table of Events (Table 4 and Table 5).  Subjects with increased signs and symptoms of EoE are 
instructed to contact the Investigator and/or study staff to determine if an EoE Flare Assessment 
Visit is warranted.
An EoE Flare Assessment Visit including safety and efficacy evaluations can occur at any time 
during the study.  An EGD is required at EoE Flare Assessment Visits 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 EoE symptoms or flare, 
medical record source data including details of the endoscopic procedure should be collected for 
the EoE 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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Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
88
The Investigator will confirm if the worsening of EoE symptoms requires rescue therapy and, thus, 
is deemed a severe EoE flare according to the following protocol definitions.  
Any worsening of EoE symptoms during study participation will be documented as an EoE flare. 

A severe EoE flare is defined as any worsening of EoE symptoms including a high intensity 
episode resulting in emergency department visit or hospitalization, with the need for 
endoscopic intervention (eg, for prolonged food impaction) and/or need for rescue therapy (eg, 
including but not limited to corticosteroid therapy or dilation), or a worsening of EoE 
symptoms resulting in the need for rescue therapy only without endoscopic intervention.  

A mild to moderate EoE flare is defined as any worsening of EoE symptoms without the need 
for rescue therapy or endoscopic intervention.  
ET procedures performed at the EoE Flare Assessment Visit do not need to be repeated for subjects 
who discontinue the study prematurely due to an EoE flare.
Induction Phase
In the Induction Phase, if a subject experiences a severe EoE flare requiring intervention with 
endoscopy and/or treatment with any rescue therapy (eg, including but not limited to systemic or 
swallowed topical corticosteroid therapy or dilation), the subject may continue participation in the 
Induction Phase with concomitant rescue therapy as needed until completion of the Induction 
Phase at Week 24.  The subject will not meet the entry criteria for the Maintenance Phase.  The 
subject will be eligible to enroll in the OLE Study, CC-93538-EE-002, based on the judgement of 
the Investigator after completing Week 24 of the Induction Phase.  
Subjects participating in the Induction Phase who require pharmacotherapy or dietary 
modifications prohibited by the protocol that may affect CC-93538 efficacy assessment or a 
dilation procedure will not be eligible for entry into the Maintenance Phase.  Refer to Maintenance 
entry criteria in Section 6.4.2.8.
Maintenance Phase
In the Maintenance Phase, if a subject experiences a severe EoE flare requiring intervention with 
endoscopy and/or treatment with any rescue therapy (eg, including but not limited to systemic or 
swallowed topical corticosteroid therapy or dilation), the subject may continue participation in the 
Maintenance Phase with concomitant rescue therapy as needed until completion of the 
Maintenance Phase at Week 48.  The subject will be eligible to enroll in the OLE Study, CC-
93538-EE-002, based on the judgement of the Investigator after completing the study (Week 48).  
6.4.2.8
Entry to Maintenance Phase
Following completion of Week 24 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 
Study, CC-93538-EE-002, unless permanent discontinuation from IP has occurred.  The following 
are conditions that will exclude subjects from entry to the Maintenance Phase:
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CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
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
Subjects with a severe EoE flare as described in Section 6.4.2.7

Subjects who demonstrate a significant worsening upon endoscopic assessment at Week 24 
compared to baseline as evidenced by the development of severe rings (EREFS Grade 3), a 
stricture < 10 mm, or a stricture that requires dilation, as evaluated by the Investigator;  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 Study, CC-93538-
EE-002

Subjects who are permanently discontinued from IP during the Induction Phase (before or at 
Week 24), and these subjects will not be eligible for participation in the OLE Study, CC-93538-
EE-002 (see Section 11.1)

In addition, for subjects who meet the following condition during the first 24 weeks of 
treatment (and without a severe EoE flare), a discussion with the Medical Monitor will be 
required before entry into Maintenance:

Subjects with any protocol-prohibited use of or change to diet (eg, 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 
EoE 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 24.  
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 study (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 study.
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 and 2 Safety Follow-up Visits, if applicable) at the time points outlined in the 
Table of Events (Table 4 and Table 5).
Details of the procedures to be followed for sample collection, processing, storage, shipment, and 
testing will be documented in a separate Study Laboratory Manual.
The development of 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, 
 and immunogenicity data taken 
together. Samples will be stored for additional analysis if necessary.
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Approved
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Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
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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 and Table 5). In the event that dosing occurs during a non-clinic visit day, it is 
still acceptable to obtain the serum samples. 
Details of the procedures to be followed for sample collection, processing, storage, shipment, and 
testing will be documented in a separate Study Laboratory Manual.
1.0
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6.0
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Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
91
1.0
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Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
92
1.0
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930207646
6.0
v
Approved
1.0
v


CC-93538 (BMS-986355)
Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
93
7
DESCRIPTION OF STUDY TREATMENTS
7.1
Description of Investigational Product(s)
The active ingredient of CC-93538 is a recombinant humanized IgG1 monoclonal antibody 
directed against human IL-13.
Investigational products (CC-93538 and placebo solutions for 
injection) are to be stored at 2° 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) 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.  
Specific handling and dispensing instructions associated with each presentation of IP are provided 
below.
IP in PFS
A PFS presentation containing drug product at a concentration of 150 mg/mL CC-93538 (or 
placebo) in a 1.2 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).
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 7.2.1) or administration of IP through a home 
health nurse (as outlined in Section 7.2) will be available IP administration options with the PFS.   
Additional instructions related to IP handling, preparation, and dispensation will be provided in a 
separate Study Pharmacy Manual (including an Instructions for Use document).
7.2
Treatment Administration and Schedule
The dosing schedule in the Induction and Maintenance Phases are as follows.
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CC-93538-EE-001 Amendment 1.0
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Subjects will be randomized 1:1:1 to the following treatment arms:

CC-93538 360 mg SC once weekly for 24 weeks followed by CC-93538 360 mg SC once 
weekly for 24 weeks

CC-93538 360 mg SC once weekly for 24 weeks followed by CC-93538 360 mg SC once 
every other week for 24 weeks.  During the Maintenance Phase, matching placebo will be 
administered once every other week on alternate weeks to maintain the blind. 

Matching placebo SC once weekly for 24 weeks followed by matching placebo SC once 
weekly for 24 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 24 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. 
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 24 weeks or once every other 
week for 24 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. 
During the study, 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. In Germany, 
subjects will be required to remain for observation for at least 60 minutes following the first 3 
weekly SC doses. 
The SC doses should be administered into the abdomen or other appropriate location including the 
thigh or back of the upper arm (rotating the injection site each time), avoiding any blood vessels, 
thickened or tender skin, scars, fibrous tissue, stretch marks, bruises, redness, nevi, or other skin 
imperfections.
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).
7.2.1
Self-Administration
Self-administration (defined as either by subject or by caregiver, applicable per local regulations)
will be an option for dose administration of IP by the PFS presentation.  For subjects enrolled in 
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Approved
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6.0
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Approved
1.0
v


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Protocol CC-93538-EE-001
Celgene International II Sàrl
CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
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Japan, self-administration should be performed by the subject himself/herself in principle; 
however, in the event that it is not feasible for the subject to self-administer CC-93538, IP-
administration may be performed by a family member. Subjects will be provided with an 
Instructions for Use document outlining steps for proper dose administration.
Self-administration will be dependent on the subject’s (or caregiver’s) ability to perform it and is
independent of the subject’s age.  Subjects who plan to self-administer IP will be required to 
perform at least the first 3 weekly injections using the PFS presentation onsite in the presence of 
site personnel.  The number of onsite injections may be increased based on Investigator judgement 
or other local requirements.  This will allow for additional onsite 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 onsite at the monthly scheduled study visits.  To help promote 
consistency within the data, subjects will not be allowed to “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.).  For subjects who have difficulty self-administering IP, all 
weekly dosing will need to be conducted on-site or may be coordinated through a visiting home 
nurse (where locally feasible) to administer the IP to the subject.
7.2.2
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 7.2.4 for temporary interruption of dosing, and Section 7.2.5 for criteria for 
discontinuation of dosing.
7.2.3
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).
7.2.4
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 
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Protocol CC-93538-EE-001
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Final: 01-Sep-2023
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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, 
CC-93538 should be temporarily interrupted until the following conditions are met:

For symptomatic subjects:
At least 10 days (20 days for severe/critical illness) have passed since symptoms first 
appeared or positive test result, and
At least 24 hours have passed since last fever without the use of fever-reducing 
medications, and
Symptoms (eg, cough and shortness of breath) have resolved, and
In the opinion of the Investigator, there are no COVID-19 sequelae that may place the 
subject at a higher risk of receiving investigational treatment, and
Negative follow-up molecular test for COVID-19 as required by 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 as required by 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.
7.2.5
Criteria for Discontinuation of Dosing
Dosing will be permanently discontinued (treatment discontinuation) for a subject if the subject 
experiences any of the events listed in Section 11.1 following initiation of 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 study. In order to prevent missing data, the site staff will 
ensure attempts are made to reach subjects by phone or email that do not maintain contact with the 
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Protocol CC-93538-EE-001
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CC-93538-EE-001 Amendment 1.0
Final: 01-Sep-2023
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Investigator.  Any subject discontinuing the study prematurely will be asked to complete the ET 
Visit and the Interim and the Final Safety Follow-up Visits.
7.2.6
Rescue Therapy
Subjects with a worsening of EoE symptoms requiring rescue therapy (defined as a severe EoE 
flare; refer to Section 6.4.2.7) during the Induction or Maintenance Phase may continue to 
participate in the phase of the study in which the EoE flare occurs.  Rescue therapy includes EoE 
standard of care pharmacotherapy, dietary modification (eg, food elimination diet), and/or dilation 
procedure.
7.3
Method of Treatment Assignment
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 1:1:1 to receive one of 2 active CC-93538 treatment arms (360 mg SC weekly for 48 
weeks or 360 mg SC weekly for 24 weeks followed by 360 mg SC every other week for 24 weeks) 
or matching placebo for 48 weeks. Approximately 70% of the study population will be Steroid 
Inadequate Responders/Intolerant.  Enrollment will be closely monitored, and enrollment of 
Steroid Responders/Naïve subjects will be limited to approximately 30%, if necessary.  Treatment 
assignment at baseline will be stratified based on steroid responder status to ensure an equal 
balance in the treatment arms.  Randomization will be performed through the Interactive Web 
Response System (IWRS) system.  
Treatment groups are described in Section 7.2. The treatment each subject will receive will not be 
disclosed to the Investigator, study center personnel, subject, Sponsor or their representatives. The 
treatment codes will be held according to the IWRS. Further instructions will be provided in a 
separate IWRS manual.  
The study blind should be maintained for persons responsible for the ongoing conduct of the study 
(after all subjects have completed the Week 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 (CRAs). For details of the emergency 
procedure for unblinding of individual subjects, see Section 11.4.
7.4
Packaging and Labeling
The label(s) for IP will include Sponsor name, address and telephone number, the protocol number, 
IP name, dosage form and strength (where applicable), amount of IP per container, lot number, 
expiry date (where applicable), medication identification/kit number, dosing instructions, storage
conditions, and required caution statements and/or regulatory statements as applicable. Additional 
information may be included on the label as applicable per local regulations.  For the PFS 
presentation, a label cover on the active and placebo syringes will be used to maintain the blind.
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Final: 01-Sep-2023
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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 clinical 
research organization (CRO) will verify that a final report of drug accountability is prepared and 
maintained in the Investigator Trial Master File.
7.6
Investigational Product Compliance
The Investigator must ensure that the IP will be used only in accordance with the protocol and that 
subjects are correctly instructed on how to take their IP and that each subject is fully compliant 
with their assigned dosage regimen. Investigational product non-compliance is defined as taking 
less than 80% or more than 120% of IP doses during the study.  Records of IP used and intervals 
between visits will be kept during the study. Drug accountability will be noted by the field monitor 
during site visits and at the completion of the study. The IP should be dispensed by the 
Investigator, or by a qualified individual under the Investigator’s supervision. An up-to-date 
treatment inventory/dispensing record must be maintained.
8
CONCOMITANT MEDICATIONS AND PROCEDURES
All treatments (including prescription and over the counter [OTC] medications, herbal and dietary 
supplements, dietary modifications, vaccines, and procedures) used by subjects within the 4 weeks 
(28 days) prior to 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 EoE will be documented. The 
Investigator must document all treatments received at the time of the EGD (for any indication) 
through Day 1.  
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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:

Subjects must agree to maintain a stable diet from the first Screening Visit and throughout the 
duration of the study.  Subjects must have maintained a stable diet for at least 4 weeks prior to 
the first Screening Visit and throughout the duration of the study.  Subjects on a food 
elimination diet for the treatment of food allergy or EoE 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 study.  However, following IP administration, subjects 
experiencing a severe EoE flare requiring a dietary modification for rescue therapy may be 
eligible to continue in the study according to protocol requirements. See Section 6.4.2.7.

Subjects may use inhaled corticosteroids, leukotriene receptor antagonists (eg, montelukast), 
or mast cell stabilizers (eg, cromolyn sodium) for indications other than EoE if on stable 
doses/regimens for at least 4 weeks prior to the first Screening Visit and regimens will remain 
stable throughout the duration of the study.  If one of these medications was recently 
discontinued, it must have been discontinued at least 4 weeks prior to the first Screening Visit.

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 duration of the study.  If
the medication was recently discontinued, it must have been discontinued at least 4 weeks prior 
to the first Screening Visit.

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 PPI medication at the first Screening Visit may participate if the PPI has 
been maintained at a stable dose from at least 4 weeks prior to the first Screening Visit through 
the end of the study. Subjects who discontinued a PPI must not have received a PPI for at least 
4 weeks before the First Screening Visit and must agree not to restart a PPI during the study.  
However, following IP administration, subjects experiencing a severe EoE flare requiring the
addition of a PPI or modification to the PPI regimen for rescue therapy may be eligible to 
continue in the study according to protocol requirements.  See Section 6.4.2.7.

Subjects receiving SC immunotherapy (treatment to desensitize to an allergen) must have been
on stable doses for at least 3 months prior to the first Screening Visit and for the duration of 
the study.

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 into the study when 
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Protocol CC-93538-EE-001
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CC-93538-EE-001 Amendment 1.0
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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 6 for a summary of the timing for stable dosing regimen requirements for certain 
medications and requirement of stable diet.
8.1.1
Rescue Therapy
During the study, subjects with a worsening of EoE symptoms requiring rescue therapy (defined 
as a severe EoE flare; refer to Section 6.4.2.7) may be eligible to continue to participate in the 
study according to protocol requirements.  Rescue therapy includes EoE standard of care 
pharmacotherapy, dietary modification (eg, food elimination diet), and/or dilation procedure.  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 EoE flare
following IP administration.  
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 EoE flare requiring rescue therapy and in such cases, subjects may continue participation 
with concomitant rescue therapy:

Subjects may not use systemic immunosuppressive or immunomodulating drugs (including 
but not limited to, Janus kinase [JAK] inhibitors, phosphodiesterase-4 [PDE-4] inhibitors, anti-
IL-13 antibodies other than IP in this study, IL-4 receptor alpha antagonist, anti-IL-5 
antibodies, anti-IL-17 antibodies, anti-IgE antibodies, α4β7 integrin inhibitor antibodies, or 
any other monoclonal antibodies, methotrexate, cyclosporine, azathioprine, mercaptopurine, 
interferon alpha [IFNα], tumor necrosis factor alpha [TNFα] inhibitors, etc.) for at least 5 drug 
half-lives prior to the first Screening Visit and during the study.
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 EoE 
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 or swallowed topical corticosteroid medication from the first 
Screening Visit through the end of the study. Subjects who have received corticosteroid 
therapy for EoE or another indication must have not received a systemic corticosteroid within 
8 weeks or a swallowed topical corticosteroid within 4 weeks of the first Screening Visit. 
However, if a subject experiences a severe EoE flare during study participation following IP 
administration, the subject may continue participating with concomitant corticosteroid rescue 
therapy according to protocol pre-specified criteria (see Section 6.4.2.7).  

Subjects may not use high potency topical corticosteroids (eg, augmented betamethasone 
dipropionate, clobetasol propionate, etc.) for dermatologic conditions from the first Screening 
Visit through the end of the study.  Subjects must not have received high potency topical 
corticosteroids for dermatologic use within 8 weeks of the first Screening Visit.
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
Subjects may not use leukotriene receptor antagonists (eg, montelukast) or mast cell stabilizers 
(eg, cromolyn sodium) for the indication of EoE from the first Screening Visit through the end 
of the study.  Subjects must not have received leukotriene receptor antagonists or mast cell 
stabilizers for EoE within 4 weeks of the first Screening Visit.

Subjects may not receive oral or sublingual immunotherapy (treatment to desensitize to an 
allergen) from the first Screening Visit through the end of the study. Subjects should not have 
received oral or sublingual immunotherapy within 6 months prior to the first Screening Visit.

Subjects may not receive live attenuated vaccines from the first Screening Visit through the 
end of the study. Subjects must not have received a live attenuated vaccine within 1 month of 
the first Screening Visit.

Subjects may not undergo esophageal dilation for EoE symptom relief during the Screening 
Period or throughout the duration of the study or have had a dilation procedure within 8 weeks 
of the first Screening Visit.  However, if a subject experiences a severe EoE flare following IP 
administration, the subject may continue participating with a concomitant dilation procedure 
for rescue therapy according to protocol pre-specified criteria (see Section 6.4.2.7).

Concurrent treatment with another IP including an investigational treatment or 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 signing the informed consent/assent 
form for this 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 6 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 6:
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
Systemic immunosuppressive or immunomodulating drugs
5 half-lives
Systemic corticosteroids
8 weeks
Swallowed topical corticosteroids
4 weeks
High potency topical corticosteroids 
8 weeks
Leukotriene receptor antagonists or mast cell stabilizers (for the 
indication of EoE)
4 weeks
Oral or sublingual immunotherapy
6 months
Live attenuated vaccines
1 month
Dilation
8 weeks
Any other investigational producta
5 half-lives
Medication (or diet)
Subjects must be on stable dosing regimens 
within the timeframe below before the first 
Screening Visit
Diet (eg, food elimination diet)
4 weeks
Inhaled corticosteroids, leukotriene receptor antagonists, or 
mast cell stabilizers (for indications other than EoE)
4 weeks
Proton pump inhibitors 
4 weeks
Medium potency topical corticosteroids
4 weeks
Subcutaneous immunotherapy
3 months
a For subjects who received an investigational COVID-19 vaccine as part of a clinical trial prior to the first Screening 
Visit, enrollment must be delayed until the biologic impact of the vaccine is stabilized, as determined by discussion 
between the Investigator and the Clinical Trial Physician. 
8.3
Required Concomitant Medications and Procedures
See inclusion criteria (Section 4.2) for a description of PPI medication requirements and 
corticosteroid treatment requirements for study eligibility. See Section 6.1 for screening EGD
requirements.
9
STATISTICAL CONSIDERATIONS
9.1
Overview
This is a Phase 3, 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. The study will incorporate a 24-week Induction Phase followed by 
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a 24-week Maintenance Phase. 
Subjects will be randomized according to the following 
stratification factor: Steroid Inadequate Responders/Intolerant status (yes or no). An independent 
Data Monitoring Committee (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.  The final database lock will be performed at the end of the study 
including data for any additional subjects who completed the Safety Follow-up Period after the 
time the last subject completes Week 48 and any updates for adverse events previously ongoing at 
the time of the primary database lock. The additional data between the primary database lock and 
last subject completing last visit in this study will be summarized in an addendum to the primary 
CSR.
Analysis details not explained in the statistical section of the protocol will be provided in the 
Statistical Analysis Plan (SAP).  In addition, the statistical analysis for the EU will be described 
in the 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
A total sample size of 399 subjects (266 subjects for CC-93538 and 133 subjects for placebo) with 
a 20% dropout rate at the end of the Induction Phase (212 subjects for CC-93538 and 106 subjects 
for placebo) will provide at least 90% power to detect a difference of -2.79 change in DD from 
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baseline at Week 24 and at least 90% power to detect a difference of 15% at Week 24 in histologic 
response with a two-sided significance level (alpha) of 0.05. These calculations were based on a 
2 sample t-test assuming a pooled standard deviation of 4.76 for change in DD from baseline and 
the chi-square test to compare the difference in 2 independent proportions for the histologic 
response assuming that the true placebo response proportion is 0.05.
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
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 Co-primary Endpoints
9.6.1.1
Overview of Attributes of the Main Estimand for the Co-primary 
Endpoints
The main estimand of interest for the co-primary endpoints are provided in Table 7 and Table 8.
For intercurrent event (ICE) number 1, the treatment policy estimand strategy will be used where 
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 number 2, a composite variable estimand 
strategy will be used where data after rescue therapy or prohibited medication which may impact 
the efficacy assessment will be set as non-responders for histologic response and worst possible 
value for change in DD.
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Table 7:
Summary of Attributes of the Main Estimand for the Co-primary 
Endpoint - Change in DD from Baseline at Week 24
Estimand 
Attribute
Definition for Co-primary Endpoint Clinical Response
Treatment
Randomized treatments with or without use of rescue therapy/prohibited medication
Population
Adult and adolescent patients with EoE
Variable
Change in DD from baseline at Week 24
Intercurrent 
Events (ICEs)
Event
Strategy
Description/Rationale
ICE 1: Treatment discontinuation in subjects 
without the use of concomitant rescue therapy or 
prohibited medication before the planned 24 
weeks
Treatment 
Policy 
Observations post ICE 
are used to reflect
clinical practice
ICE 2: The use of concomitant rescue therapy or 
prohibited medication which may impact the 
efficacy assessment for CC-93538, regardless of 
treatment discontinuation, before the planned 24 
weeks
Composite 
Variable
Data post ICE will be 
set as worst possible 
value to reflect 
treatment failure
Population-
level Summary
Difference in mean changes between treatment groups
Table 8:
Summary of Attributes of the Main Estimand for the Co-primary 
Endpoint - Histologic Response at Week 24
Estimand 
Attribute
Definition for Co-primary Endpoint Histologic Response
Treatment
Randomized treatments with or without use of rescue therapy/prohibited medication
Population
Adult and adolescent patients with EoE
Variable
Peak esophageal eosinophil count ≤6 eos/hpf at Week 24
Intercurrent 
Events (ICEs)
Event
Strategy
Description/Rationale
ICE 1: Treatment discontinuation in subjects 
without the use of concomitant rescue therapy or 
prohibited medication before the planned 24 
weeks
Treatment 
Policy 
Observations post ICE 
are used to reflect 
clinical practice
ICE 2: The use of concomitant rescue therapy or 
prohibited medication which may impact the 
efficacy assessment for CC-93538, regardless of 
treatment discontinuation, before the planned 24 
weeks
Composite 
Variable
Data post ICE will be 
set as non-responders to 
reflect treatment failure
Population-
level Summary
Difference in proportions between treatment groups
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9.6.1.2
Change in Dysphagia Days (DD) from Baseline to Week 24 (Induction 
Phase)
The mean change in dysphagia days (DD), evaluated over the prior 14-day period using the mDSD, 
from baseline to Week 24 is one of the 2 co-primary endpoints for the Induction Phase.  
A DD is defined as a “yes” response to any or all of mDSD questions 2, 3, and 4.  In calculating 
the number of DD for each subject, if the number of measurable diary days (defined as a diary day 
for which Questions 2 to 4 are answered) over the 14-day period prior to Day 1 is less than 11 or 
post-Day 1 visits are less than 8, the normalization formula will not be applied and the value of 
DD will be set to missing. In addition, subjects with at least 8 measurable diary days at post-Day 
1 visits that are very unbalanced across the two weeks, defined as less than 3 measurable diary 
days in either the first or second week, will also have the value of DD set to missing.
The primary analysis will be conducted on the ITT population based on an analysis of covariance 
(ANCOVA) model with treatment group, Steroid Inadequate Responders/Intolerant status (yes or 
no), and baseline DD values included in the model. The comparison between CC-93538 360 mg 
SC once weekly and placebo for change in DD from baseline at Week 24 will be made using the 
difference in least squares (LS) mean at a 5% 2-sided significance level.  Point estimates for the 
mean difference between the 2 treatment groups using the adjusted LS Mean changes and 
corresponding 95% Wald CI will be reported. In addition, adjusted LS Means with standard error 
(SE), arithmetic means with standard deviation (SD), and arithmetic mean changes with SD will 
be summarized by treatment group.
Missing data will be handled using a multiple imputation (MI) approach (SAS Institute, 2015) 
under a missing at random (MAR) assumption.
The following sensitivity analyses will be performed to support the main estimand analysis and 
provide additional insights to understand the treatment effect:  

Robustness due to missing data MI under MAR assumption will be explored using tipping 
point analysis (Yan, 2009; Campbell, 2011; Yuan, 2014). 

A minimum of 4 measurable diary days per week is required to derive a DD score for the 14-
day period. The analysis method will be the same as the primary analysis. 
In considering the ICEs of study interest (ie, ICE number 2, use of rescue therapy/prohibited 
medication), supplementary analyses will be performed using the treatment policy estimand 
strategy and a hypothetical estimand strategy.  In addition to the overall population, change in DD 
from baseline to Week 24 will be analyzed in the Steroid Inadequate Responders/Intolerant 
subgroup. This analysis will be similar to the overall population except that the ANCOVA model 
will not include Steroid Inadequate Responders/Intolerant status. See Section 9.6.4 for details on 
the hierarchical testing procedure to control the Type I error rate.
9.6.1.3
Eosinophilic Histologic Response at Week 24 (Induction Phase)
The other co-primary endpoint, eosinophilic histologic response, is defined as a peak esophageal 
eosinophil count ≤ 6/hpf (across all available esophageal levels) at Week 24. 
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The primary analysis of the eosinophilic histologic response will be conducted on the ITT 
population using the CMH test at a 2-sided 5% significance level, stratified by Steroid Inadequate 
Responders/Intolerant status. For treatment comparison between CC-93538 360 mg SC once 
weekly and placebo, the 2-sided 95% CI for the difference in proportions using the CMH weights 
and the 2-sided p-value from the CMH test will be provided. 
Missing data in subjects without use of rescue therapy/prohibited medication prior to Week 24 will 
be handled using a multiple imputation (MI) approach (SAS Institute, 2015) under a missing at 
random (MAR) assumption.
A sensitivity analysis will be performed using tipping point analysis to assess the robustness of the 
primary efficacy analysis with regards to handling of missing data.  
In considering the ICEs of study interest (ie, ICE number 2, use of rescue therapy or prohibited 
medication which may impact the efficacy assessment), a supplementary analysis using the 
treatment policy estimand strategy for the histologic endpoint at Week 24 will be conducted.  
In addition to the overall population, histologic response at Week 24 will be analyzed in the Steroid 
Inadequate Responders/Intolerant subgroup. This analysis will be similar to the overall population 
except that the analysis will be done using the chi-square test. See Section 9.6.4 for details on the 
hierarchical testing procedure to control the Type I error rate.
9.6.2
Analysis of Key Secondary Efficacy Endpoints 
For the first key secondary endpoint, proportion of subjects achieving eosinophilic histologic 
response defined as a peak esophageal eosinophil count < 15/hpf (across all available esophageal 
levels) at Week 24, the main analysis will be conducted based on the ITT population using the 
same type of method as described for the histologic response at Week 24 (the co-primary 
endpoint). The same summary and inferential statistics will be reported as specified for the 
primary analysis of the co-primary endpoint of histologic response in Section 9.6.1.3. Missing 
data and ICEs of interest will be handled via the same strategy as for the primary analysis of the 
co-primary endpoint of histologic response.
For the second key secondary endpoint, mean change in the endoscopic features of EoE as 
measured by the EoE Endoscopic Reference Score (EREFS) from baseline to Week 24, the main 
analysis will be conducted based on the ITT population using an ANCOVA model with treatment 
group, Steroid Inadequate Responders/Intolerant status (yes or no), and baseline EREFS values 
included in the model. The same summary and inferential statistics will be reported as specified 
for the primary analysis of the co-primary endpoint of change in DD in Section 9.6.1.2. Missing 
data and ICEs of interest will be handled via the same strategy as for the primary analysis of the 
co-primary endpoint of change in DD.
For the third key secondary endpoint, mean change in the mean adjusted histology grade score as 
measured by the scoring system (EoEHSS) from baseline to Week 24, the main analysis will be 
conducted based on the ITT population using an ANCOVA model with treatment group, Steroid 
Inadequate Responders/Intolerant status (yes or no), and baseline mean adjusted histology grade 
score values included in the model. The same summary and inferential statistics will be reported 
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as specified for the primary analysis of the co-primary endpoint of change in DD in Section 9.6.1.2. 
Missing data and ICEs of interest will be handled via the same strategy as for the primary analysis 
of the co-primary endpoint of change in DD.
For the fourth key secondary endpoint, mean change in the mean adjusted histology stage score as 
measured by the scoring system (EoEHSS) from baseline to Week 24, the main analysis will be 
conducted based on the ITT population using an ANCOVA model with treatment group, Steroid 
Inadequate Responders/Intolerant status (yes or no), and baseline mean adjusted histology stage 
score values included in the model. The same summary and inferential statistics will be reported 
as specified for the primary analysis of the co-primary endpoint of change in DD in Section 9.6.1.2. 
Missing data and ICEs of interest will be handled via the same strategy as for the primary analysis 
of the co-primary endpoint of change in DD.
For the fifth key secondary endpoint, mean change in mDSD composite score from baseline to 
Week 24, the main analysis will be conducted based on the ITT population using an ANCOVA 
model with treatment group, Steroid Inadequate Responders/Intolerant status (yes or no), and 
baseline mDSD composite score values included in the model. The same summary and inferential 
statistics will be reported as specified for the primary analysis of the co-primary endpoint of change 
in DD in Section 9.6.1.2. Missing data and ICEs of interest will be handled via the same strategy 
as for the primary analysis of the co-primary endpoint of change in DD.
For the binary endpoint (the first key secondary endpoint), a supplementary analysis using the 
treatment policy estimand strategy will also be conducted.
All observed data will be used 
regardless of ICE. 
For continuous endpoints (second to fifth key secondary endpoints), supplementary analyses using 
the treatment policy estimand strategy and a hypothetical estimand strategy to handle ICEs of 
rescue therapy/prohibited medication use will also be conducted.  Data will be analyzed using the 
same ANCOVA model as described in this section.
9.6.3
Analysis of Secondary Efficacy Endpoints 
End of Maintenance Phase (Week 48):
Histologic Response: The analysis of the histologic response endpoint will be conducted on the 
ITT population using the CMH test stratified by Steroid Inadequate Responders/Intolerant status. 
For treatment comparison between a CC-93538 dose and placebo, the 2-sided 95% CI for the 
difference in proportions using the CMH weights will be provided. Missing data will be handled 
via the same strategy as for the primary analysis of the co-primary endpoint of histologic response.
Mean change in DD: For the analysis of change in DD from baseline at Week 48, the baseline is 
defined as the last visit prior to receiving any dose of CC-93538 360 mg or placebo in the Induction 
Phase.  The analysis of change in DD from baseline at Week 48 will be conducted using an 
ANCOVA model with treatment group (CC-93538 360 mg SC once weekly, CC-93538 360 mg 
SC once every other week, and placebo), Steroid Inadequate Responders/Intolerant status (yes or 
no), and baseline DD values included in the model. Point estimates for the mean difference 
between the treatment groups using the adjusted LS Mean changes and corresponding 95% Wald 
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CI will be reported. Missing data will be handled via the same strategy as for the primary analysis 
of the co-primary endpoint of change in DD.
In addition to the overall population, histologic response at Week 48 and change in DD from 
baseline to Week 48 will be analyzed in the Steroid Inadequate Responders/Intolerant subgroup.  
These analyses will be similar to the overall population except that the analysis will be done using 
the chi-square test and the ANCOVA model will not include Steroid Inadequate 
Responders/Intolerant status.  See Section 9.6.4 for details on the hierarchical testing procedure to 
control the Type I error rate.
9.6.4
Control of the Type I Error Rate
A hierarchical testing procedure will be utilized to permit confirmatory assessment of the co-
primary endpoints, 5 key secondary endpoints, and 2 secondary endpoints at Week 48 in the overall 
population.  In addition, the hierarchical testing procedure includes confirmatory assessment of 
the co-primary endpoints and two secondary endpoints at Week 48 in the Steroid Inadequate 
Responders/Intolerant subgroup.  The Type I error rate is controlled for multiplicity (Dmitrienko, 
2013).
Figure 2 presents the schematic for the hierarchical testing procedure for the United States and 
other non-European Union regions. A fixed sequence test will be applied and each hypothesis will 
be tested sequentially at an α level of 0.05.  For the 2 co-primary endpoints, both p-values need to 
be less than α to continue to test the next endpoint of the sequence.  For this hierarchy, the result(s) 
will be considered confirmatory if all previously tested hypotheses in the hierarchy are statistically 
significant at α = 0.05.
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Figure 2:
Multiplicity Adjustment for the US and Other Non-EU Regions
Abbreviations:  DD = dysphagia day(s); EoE = eosinophilic esophagitis; EoEHSS = EoE histology scoring system; 
eos = eosinophils; EREFS = EoE Endoscopic Reference Score; hpf = high-power field; ITT = intent-to-treat; mDSD 
= modified daily symptom diary; SIR-I = Steroid Inadequate Responders/Intolerant; WK = week
Note:  p1 and p2 represent the p-values for the 1st co-primary endpoint of change in DD and 2nd co-primary endpoint 
of histologic response, respectively.
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For the EU, 2 additional endpoints in the Induction Phase will be included in the hierarchy: 

The proportion of subjects with a ≥ 50% decrease in dysphagia days (DD) from baseline at 
Week 24

The proportion of subjects who achieve histologic response defined as a peak esophageal 
eosinophil count ≤ 6/hpf at Week 24 and dysphagia symptom response defined as the 
proportion of subjects with ≥ 50% decrease in dysphagia days (DD) from baseline at Week 24
Details of the hierarchy for the EU analysis will be discussed in the SAP.
9.6.5
Subgroup Analyses
To assess whether the treatment effect is consistent across various groups, subgroup analyses will 
be performed for the co-primary endpoints at Week 24.   Treatment differences and 2-sided 95% 
CIs will be provided for each subgroup listed below.  Forest plots for the treatment differences by 
subgroup will also be provided. 
1) Steroid Inadequate Responders/Intolerant status as reported in EDC (yes versus no) 
2) Prior history of corticosteroid use for the treatment of EoE (yes versus no)
3) Age group (adolescents [< 18 years] versus adults [≥ 18 years], non-elderly adults [18 to < 65 
years] versus elderly adults [ ≥ 65 years])
4) Previous dilation procedure for EoE (yes versus no)
5) Sex (female versus male)
6) Region (North America versus non-North America, European Union versus non-European 
Union) 
7) Presence of atopy (yes versus no)
8) On stable concomitant PPI regimen (yes versus no)
9) On stable dietary modification (eg, elimination diet for the treatment of allergy or EoE [yes 
versus no])
10) Race (white versus non-white)
9.7
Safety Analysis
All analyses of safety data will be conducted using the Safety population by treatment 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.  Individual data listings will also be provided.
Adverse events will be monitored during the trial, 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 lab. Each subject’s 
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hematology, blood chemistry, and urinalysis values will be flagged as “low”, “normal”, or “high” 
relative to the normal ranges of the central laboratory. 
Summary statistics of actual values and changes from baseline in vital signs will be provided by 
visit.
9.8
Interim Analysis
No formal interim analysis will be conducted for the study.
9.9
Other Topics
9.9.1
Pharmacokinetics, 
and 
Immunogenicity
Serum trough concentrations (Ctrough) of CC-93538 will be summarized with descriptive 
statistics by treatment and visit.  Additional analysis may be conducted as appropriate (eg, by ADA 
status).
 
Data from other studies may be included if appropriate. 
 
 
will be conducted for efficacy, safety,
 
endpoints.  Details on the studies and methodology will be outlined in a separate PK Analysis Plan,
and results will be issued separately from the clinical study report as a stand-alone report.
Immunogenicity analysis will be described in the SAP.
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 Safety Management Team (SMT).
The SMT is comprised of lead representatives from multiple Celgene functions engaged in the 
CC-93538 development program. 
The scope, conduct, processes, and accountabilities are 
specified by Celgene Standard Operating Procedure (SOP).
9.9.4
External Data Monitoring Committee 
Safety monitoring will also be performed by an external, independent Data Monitoring Committee 
(DMC). A DMC will be convened that will be comprised of physician experts with experience in 
treating subjects with EoE and a statistician, all of whom are not otherwise involved in the study 
conduct and for whom there is no identified conflict of interest. During the study, the DMC will 
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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.
9.9.5
Steering Committee 
A steering committee, which will include the coordinating Principal Investigator, other 
investigators, and experts in eosinophilic esophagitis will be empaneled and serve in an advisory 
capacity to the Sponsor.  Operational details for the steering committee will be detailed in a 
separate steering committee charter.
10
ADVERSE EVENTS
10.1
Monitoring, Recording and Reporting of Adverse Events
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in 
a subject during the course of a study. It may be a new intercurrent illness, a worsening 
concomitant illness, an injury, or any concomitant impairment of the subject’s health, including 
laboratory test values (as specified by the criteria in Section 10.3), regardless of etiology. Any 
worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre-
existing condition) should be considered an AE except for symptoms associated with an EoE flare 
requiring an EoE Flare Assessment, as referenced in Section 6.4.2.7.  However, any EoE flare that 
meets the criteria for serious as detailed in Section 10.2.1, should be documented as an SAE in 
addition to an EoE flare. A diagnosis or syndrome should be recorded on the AE page of the eCRF 
rather than the individual signs or symptoms of the diagnosis or syndrome. 
Abuse, withdrawal, sensitivity or toxicity to an investigational product should be reported as an 
AE. Overdose, accidental or intentional, whether or not it is associated with an AE should be 
reported on the overdose eCRF. (See Section 7.2 for the definition of overdose.) Any sequela of 
an accidental or intentional overdose of an investigational product which meets the definition of 
an AE, should be reported as an AE on the AE eCRF. If the sequela of an overdose meets serious 
criteria, then it must be marked as serious on the eCRF. The overdose itself should not be reported 
as an AE.
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary.  There is no known specific antidote for CC-93538 overdose. 
Actual treatment should depend on the severity of the clinical situation and the judgement and 
experience of the treating physician.
All subjects will be monitored for AEs, including AEs related to SARS-CoV-2 infection, during 
the study.  Assessments may include monitoring of any or all of the following parameters:  the 
subject’s clinical symptoms, laboratory, pathological, radiological or surgical findings, physical 
examination findings, or findings from other tests and/or procedures.  In addition, device (ie, PFS) 
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failures or malfunctions should be captured during the study, and any device related AEs should 
also be documented.
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.  All SAEs 
must be reported to Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the 
event.  
The SAE is recorded within the eCRF and the data is transmitted electronically to Celgene Drug 
Safety within 24 hours of the Investigator’s knowledge of the event. 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.
10.2
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 judgement 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.
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
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”.
For each SAE, the Investigator will provide information on severity, start and stop dates, 
relationship to the IP, action taken regarding the IP, and outcome.
10.2.2
Severity/Intensity
For both AEs and SAEs, the Investigator must assess the severity/intensity of the event. 
Mild

Asymptomatic or mild symptoms; clinical or diagnostic observations only

Intervention not indicated

Activities of daily life (ADLs) minimally or not affected

No or minimal intervention/therapy may be required 
Moderate 

Symptom(s) cause moderate discomfort

Local or noninvasive intervention indicated

More than minimal interference with ADLs but able to carry out daily social and functional 
activities

Drug therapy may be required
Severe (could be non-serious or serious) 

Symptoms causing severe discomfort/pain

Symptoms requiring medical/surgical attention/intervention

Interference with ADLs including inability to perform daily social and functional activities (eg, 
absenteeism and/or bed rest)

Drug therapy is required
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The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache).  This criterion is not the same as “serious” which is based 
on subject/event outcome or action criteria associated with events that pose a threat to a subject’s 
life or functioning.  
Seriousness, not severity, serves as a guide for defining regulatory obligations.
10.2.3
Causality
The Investigator must determine the relationship between the administration of the IP and the 
occurrence of an AE/SAE as Not Suspected or Suspected as defined below:
Not suspected:
a causal relationship of the adverse event to IP administration is unlikely or 
remote, or other medications, therapeutic interventions, or underlying 
conditions provide a sufficient explanation for the observed event.
Suspected:
there is a reasonable possibility that the administration of IP caused the 
adverse event.  ‘Reasonable possibility’ means there is evidence to suggest 
a causal relationship between the IP and the adverse event.
Causality should be assessed and provided for every AE/SAE based on currently available 
information. Causality is to be reassessed and provided as additional information becomes 
available.
If an event is assessed as suspected of being related to a comparator, ancillary or additional IP that 
has not been manufactured or provided by Celgene, please provide the name of the manufacturer 
when reporting the event.
10.2.4
Duration
For both AEs and SAEs, the Investigator will provide a record of the start and stop dates of the 
event.
10.2.5
Action Taken
The Investigator will report the action taken with IP as a result of an AE or SAE, as applicable (eg, 
discontinuation, interruption, or dose reduction of IP, as appropriate) and report if concomitant 
and/or additional treatments were given for the event. 
10.2.6
Outcome
The Investigator will report the outcome of the event for both AEs and SAEs.  After the initial 
AE/SAE report, the Investigator is required to proactively follow each subject at subsequent 
visits/contacts.  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).
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All SAEs that have not resolved upon discontinuation of the subject’s participation in the study 
must be followed until recovered (returned to baseline), recovered with sequelae, or death (due to 
the SAE).
10.3
Abnormal Laboratory Values
An abnormal laboratory value is considered to be an AE if the abnormality:

results in discontinuation from the study;

requires treatment, modification/interruption of IP dose, or any other therapeutic intervention; 
or

is judged to be of significant clinical importance, eg, one that indicates a new disease process 
and/or organ toxicity, or is an exacerbation or worsening of an existing condition.
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion need 
to be documented as 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, 
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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 SAEs.  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 
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 electronic data capture system (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 SAE 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). Additionally, AESIs will be identified by the Sponsor programmatically.  All 
AESIs must be entered into EDC within 24 hours of the Investigator’s knowledge of the event.  
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AESIs fall into a number of categories based on the safety observations from dupilumab, 
lebrikizumab, and CC-93538 clinical studies and the potential pharmacologic effects of IL-4 
receptor antagonist and anti-IL-13 antibodies. These include:

Anaphylactic reactions 

Systemic or severe hypersensitivity reactions 

Severe injection site reactions (ISR) that last longer than 24 hours

A severe ISR is defined as an ISR that manifests with symptoms causing severe 
discomfort/pain; symptoms requiring medical/surgical attention/intervention; interference
with 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.
In the US, all suspected unexpected serious adverse reactions (SUSARs) will be reported in an 
expedited manner in accordance with 21 Code of Federal Regulations (CFR) 312.32.
For countries within the European Economic Area (EEA), Celgene or its authorized representative 
will report in an expedited manner to Regulatory Authorities and Ethics Committees concerned, 
SUSARs in accordance with Directive 2001/20/EC and the Detailed Guidance on collection, 
verification and presentation of adverse reaction reports arising from clinical trials on 
investigational products for human use (ENTR/CT3) and also in accordance with country-specific 
requirements.  
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.
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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.
11
DISCONTINUATIONS
11.1
Treatment Discontinuation
The following events are considered sufficient reasons for permanently discontinuing a subject 
from the IP:

Adverse event

Physician decision

Lack of efficacy

Protocol deviation

Withdrawal by subject 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 immunocompromise

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 the abnormality was first observed):

Neutrophil count ≤ 0.5 × 103/µL

Platelet count ≤ 50 × 103/µL

ALT and/or AST values > 3 × ULN with total bilirubin > 2 × ULN or INR > 1.5, excluding 
confirmed Gilbert’s Syndrome or therapeutic anticoagulation

ALT and/or AST > 5 × ULN for greater than 2 weeks duration

3 or more consecutive missed doses 
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
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.
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 Study, CC-93538-
EE-002. 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.   
The reason for discontinuation of treatment should be recorded in the eCRF and in the source 
documents.
The decision to discontinue a subject from treatment remains the responsibility of the treating 
physician, which will not be delayed or refused by the Sponsor.  However, prior to discontinuing 
a subject from treatment, the Investigator may contact the Medical Monitor and forward 
appropriate supporting documents for review and discussion.
11.2
Study Discontinuation
The following events are considered sufficient reasons for discontinuing a subject from the study:

Withdrawal by subject or parent/guardian

Lost to follow-up

Death

Other (to be specified on the eCRF)
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.  
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 24, or who complete Week 24 and do not enter the Maintenance Phase will complete an ET 
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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 24) the ET Visit/procedures 
should be performed. These subjects, with the exception of those continuing in the OLE, 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 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 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).
11.3
Emergency Contact
In emergency situations, the Investigator should contact the responsible Clinical Research 
Physician (also referred to as Clinical Trial Physician)/Medical Monitor or designee by telephone 
at the number(s) listed on the Emergency Contact Information page of the protocol (after title 
page).
In the unlikely event that the Clinical Research Physician (also referred to as Clinical Trial 
Physician)/Medical Monitor or designee cannot be reached, please contact the global Emergency 
Call Center by telephone at the number listed on the Emergency Contact Information page of the 
protocol (after title page). This global Emergency Call Center is available 24 hours a day and 7 
days a week. The representatives are responsible for obtaining your call-back information and 
contacting the on-call Celgene/contract research organization Medical Monitor, who will then 
contact you promptly.
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s), also referred to as Clinical Trial Physician(s),
or Medical Monitor or designee for emergency calls. 
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.
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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 unblinded dose information.
12
REGULATORY CONSIDERATIONS
12.1
Good Clinical Practice
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative, and 
Investigator abide by Good Clinical Practice (GCP), as described in International Council for
Harmonisation (ICH) Guideline E6 and in accordance with the general ethical principles outlined 
in the Declaration of Helsinki. The study will receive approval from an IRB/EC prior to 
commencement. The Investigator will conduct all aspects of this study in accordance with 
applicable national, state, and local laws of the pertinent regulatory authorities.
12.2
Investigator Responsibilities
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in the 
local regulations.  Celgene staff or an authorized representative will evaluate and approve all 
Investigators who in turn will select their staff.
The Investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions, 
including obligations of confidentiality of Celgene information. The Investigator should maintain 
a list of Sub-investigators and other appropriately qualified persons to whom he or she has 
delegated significant study-related duties.
The Investigator is responsible for keeping a record of all subjects who sign an informed consent 
form (ICF/assent) and are screened for entry into the study.  Subjects who fail screening must have 
the reason(s) recorded in the subject’s source documents.
The Investigator, or a designated member of the Investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (eg, 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification.  The Investigator must ensure timely and accurate completion of eCRFs and queries.
The information contained in the protocol and amendments (with the exception of the information 
provided by Celgene on public registry websites) is considered Celgene confidential information.  
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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.
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.
Documentation that informed consent/assent occurred prior to the study subject’s entry into the 
study and of the informed consent/assent process should be recorded in the study subject’s source 
documents including the date.  The original ICF/assent signed and dated by the study subject and 
by the person consenting the study subject prior to the study subject’s entry into the study, must 
be maintained in the Investigator’s study files and a copy given to the study subject.  In addition, 
if a protocol is amended and it impacts on the content of the informed consent/assent, the 
ICF/assent must be revised.  Study subjects participating in the study when the amended protocol 
is implemented must be re-consented/assented with the revised version of the ICF/assent.  The 
revised ICF/assent signed and dated by the study subject and by the person consenting the study 
subject must be maintained in the Investigator’s study files and a copy given to the study subject.
In Austria, Germany, Spain, and Switzerland, adolescent subjects will not be enrolled.
12.4
Confidentiality
Celgene affirms the subject's right to protection against invasion of privacy and to be in compliance 
with ICH and other local regulations (whichever is most stringent). Celgene requires the 
Investigator to permit Celgene's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local laws.
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF/assent, it is the responsibility of the Investigator to obtain such permission in 
writing from the appropriate individual.
12.5
Protocol Amendments
Any amendment to this protocol must be approved by the Celgene Clinical Research Physician
(also referred to as Clinical Trial Physician)/Medical Monitor.  Amendments will be submitted to 
the IRB/EC for written approval.  Written approval must be obtained before implementation of the 
amended version occurs.  The written signed approval from the IRB/EC should specifically 
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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/EC approval but will 
be submitted to the IRB/EC for information purposes.
12.6
Institutional Review Board/Independent Ethics Committee Review and 
Approval
Before the start of the study, the study protocol, ICF/assent, and any other appropriate documents 
will be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their 
dates of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is 
sought. If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements.
IP can only be supplied to an Investigator by Celgene or its authorized representative after 
documentation on all ethical and legal requirements for starting the study has been received by 
Celgene or its authorized representative. This documentation must also include a list of the 
members of the IRB/EC and their occupation and qualifications. If the IRB/EC will not disclose 
the names, occupations and qualifications of the committee members, it should be asked to issue 
a statement confirming that the composition of the committee is in accordance with GCP. For 
example, the IRB General Assurance Number may be accepted as a substitute for this list. Formal 
approval by the IRB/EC should mention the protocol title, number, amendment number (if 
applicable), study site (or region or area of jurisdiction, as applicable), and any other documents 
reviewed. It must mention the date on which the decision was made and must be officially signed 
by a committee member. Before the first subject is enrolled in the study, all ethical and legal 
requirements must be met.
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF/assent should also be 
revised.
The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating Investigator and the IRB/EC. This statement also applies to any 
communication between the Investigator (or Coordinating Investigator, if applicable) and 
regulatory authorities.
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB/EC prior to use.
12.7
Ongoing Information for Institutional Review Board/ Ethics Committee
If required by legislation or the IRB/EC, the Investigator must submit to the IRB/EC:

Information on serious or unexpected adverse events as soon as possible; 

Periodic reports on the progress of the study;

Deviations from the protocol or anything that may involve added risk to subjects.
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12.8
Termination of the Study
Celgene reserves the right to terminate this study prematurely at any time for reasonable medical 
or administrative reasons.
Any premature discontinuation will be appropriately documented
according to local requirements (eg, IRB/EC, regulatory authorities, etc.).
In addition, the Investigator or Celgene has the right to discontinue a single site at any time during 
the study for medical or administrative reasons such as:

Unsatisfactory enrollment;

GCP non-compliance;

Inaccurate or incomplete data collection;

Falsification of records;

Failure to adhere to the study protocol.
13
DATA HANDLING AND RECORDKEEPING 
13.1
Data/Documents
The Investigator must ensure that the records and documents pertaining to the conduct of the study 
and the distribution of the investigational product are complete, accurate, filed and retained.  
Examples of source documents include: hospital records; clinic and office charts; laboratory notes; 
memoranda; subject’s diaries or evaluation checklists; dispensing records; recorded data from 
automated instruments; copies or transcriptions certified after verification as being accurate copies; 
microfiche; x-ray film and reports; and records kept at the pharmacy, and the laboratories, as well 
as copies of eCRFs/case report forms (CRFs) or CD-ROM.
13.2
Data Management
Data will be collected via eCRF and entered into the clinical database per Celgene SOPs. This 
data will be electronically verified through use of programmed edit checks specified by the clinical 
team.  Discrepancies in the data will be brought to the attention of the clinical team, and 
investigational site personnel, if necessary.  Resolutions to these issues will be reflected in the 
database.  An audit trail within the system will track all changes made to the data.
13.3
Record Retention
Essential documents must be retained by the Investigator according to the period of time outlined 
in the Clinical Trial Agreement.  The Investigator must retain these documents for the time period 
described above or according to local laws or requirements, whichever is longer. Essential 
documents include, but are not limited to, the following:

Signed ICFs/assent for all subjects;

Subject identification code list, screening log (if applicable), and enrollment log;

Record of all communications between the Investigator and the IRB/EC;

Composition of the IRB/EC;
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
Record of all communications between the Investigator, Celgene, and their authorized 
representative(s);

List of Sub-investigators and other appropriately qualified persons to whom the Investigator 
has delegated significant study-related duties, together with their roles in the study, curriculum 
vitae, and their signatures;

Copies of CRFs (if paper) and of documentation of corrections for all subjects;

IP accountability records;

Record of any body fluids or tissue samples retained;

All other source documents (subject records, hospital records, laboratory records, etc.); 

All other documents as listed in Section 8 of the ICH consolidated guideline on GCP (Essential 
Documents for the Conduct of a Clinical Trial).
The Investigator must notify Celgene if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period.  
The Investigator must obtain approval in writing from Celgene prior to destruction of any records.  
If the Investigator is unable to meet this obligation, the Investigator must ask Celgene for 
permission to make alternative arrangements. 
Details of these arrangements should be 
documented. 
All study documents should be made available if required by relevant health authorities. 
Investigator or institution should take measures to prevent accidental or premature destruction of 
these documents.
14
QUALITY CONTROL AND QUALITY ASSURANCE
All aspects of the study will be carefully monitored by Celgene or its authorized representative for 
compliance with applicable government regulations with respect to current GCP and SOPs.
14.1
Study Monitoring and Source Data Verification
Celgene ensures that appropriate monitoring procedures are performed before, during and after the 
study.  All aspects of the study are reviewed with the Investigator and the staff at a study initiation 
visit and/or at an Investigators’ Meeting.  Prior to enrolling subjects into the study, a Celgene 
representative will review the protocol, eCRFs, procedures for obtaining informed consent, record 
keeping, and reporting of AEs/SAEs with the Investigator.  Monitoring will include on-site visits 
with the Investigator and his/her staff as well as any appropriate communications by mail, email, 
fax, or telephone.  During monitoring visits, the facilities, investigational product storage area, 
eCRFs, subject’s source documents, and all other study documentation will be inspected/reviewed 
by the Celgene representative in accordance with the Study Monitoring Plan.
Accuracy will be checked by performing source data verification that is a direct comparison of the 
entries made onto the eCRFs against the appropriate source documentation.  Any resulting 
discrepancies will be reviewed with the Investigator and/or his/her staff.  Any necessary 
corrections will be made directly to the eCRFs or via queries by the Investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
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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 the study Clinical Trial Monitor and/or Clinical Trial Manager or 
designee. Report an issue or concern with all sponsor supplied IMP, non-investigational medicinal 
product (NIMP) or auxiliary medicinal product (AxMP), suspected to have occurred before the 
product was transferred to the responsibility of the investigational site (eg, during manufacturing, 
packaging and labeling, storage, and/or distribution).
This includes suspected quality issues of components co-packaged with the drug, labeling, 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 the 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.
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 
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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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oesophagitis in children and adults in population-based studies. Aliment Pharmacol Ther. 2019 
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Zuo L, Fulkerson PC, Finkelman FD, Mingler M, Fischetti CA, Blanchard C, et al. IL-13 induces 
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17
APPENDICES
APPENDIX A
TABLE OF ABBREVIATIONS
Table 9:
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
AI
Autoinjector
ALT
Alanine aminotransferase
ANCOVA
Analysis of covariance
aPTT
Activated partial thromboplastin time
AST
Aspartate aminotransferase
AUC
Area under the curve
β-hCG
β-subunit of human chorionic gonadotropin
BMS
Bristol-Myers Squibb Company
CFR
Code of Federal Regulations
CI
Confidence interval
Cmax 
Observed maximum serum concentration
CMH
Cochran-Mantel-Haenszel
COVID-19
Coronavirus disease 2019
CPK
Creatine phosphokinase
CRA
Clinical Research Associate
CRF
Case report form
CRP
C-reactive protein
CSR
Clinical study report
DB
Double-blind
Ctrough
Serum trough concentration
DD
Dysphagia day(s)
DMC
Data Monitoring Committee
DNA
deoxyribonucleic acid
DSD
Daily Symptom Diary
EC
Ethics Committee
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Table 9:
Abbreviations and Specialist Terms
Abbreviation or Specialist Term
Explanation
EC50
Half maximal effective concentration
ECG
Electrocardiogram 
eCRF
Electronic case report form
EDC
Electronic data capture system
eDiary
Electronic diary
EEA
European Economic Area 
EGD
Esophagogastroduodenoscopy
ELISA
enzyme-linked immunosorbent assay 
EMA
European Medicines Agency
EoE
Eosinophilic esophagitis
EoEHSS
EoE histology scoring system
eos
Eosinophils
ePRO
Electronic patient-reported outcome
EREFS
EoE Endoscopic Reference Score
ET
Early Termination
EU
European Union
FCBP
Female of childbearing potential
FDA
Food and Drug Administration
GADS-S
Global Assessment of Disease Severity-Subject
GCP
Good Clinical Practice
GERD
Gastroesophageal reflux disease
GGT
Gamma glutamyltransferase
GI
Gastrointestinal
GIC-EoE
Global Impression of Change in EoE Symptoms
H&E
Hematoxylin and eosin
HBcAb
Hepatitis B core antibody 
HBsAg
Hepatitis B surface antigen 
HBV
Hepatitis B virus
Hct
Hematocrit
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Table 9:
Abbreviations and Specialist Terms
Abbreviation or Specialist Term
Explanation
HCV
Hepatitis C virus
Hgb
Hemoglobin
HIV
Human immunodeficiency virus
hpf
High-power field 
IB
Investigator’s Brochure
ICE
Intercurrent event
ICF
Informed consent form
ICH
International Council for Harmonisation
IFNα
Interferon alpha
IgE
Immunoglobulin E
IgG
Immunoglobulin G
IgG1κ
Immunoglobulin G1 kappa
IGRA
Interferon gamma release assay
IMP
Investigational medicinal product
IL-4
Interleukin-4
IL-5
Interleukin-5
IL-13
Interleukin-13
IL-13Rα1
Interleukin-13 receptor alpha 1
IL-13Rα2
Interleukin-13 receptor alpha 2
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/ly
IWRS
Interactive Web Response System
LS
Least squares
mAb
Monoclonal antibody
MAR
Missing at random
MCH
Mean corpuscular hemoglobin 
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Table 9:
Abbreviations and Specialist Terms
Abbreviation or Specialist Term
Explanation
MCHC
Mean corpuscular hemoglobin concentration
MCV
Mean corpuscular volume
mDSD
Modified Daily Symptom Diary
MI
Multiple imputation
OLE
Open-Label Extension
PFS
Pre-filled syringe(s)
PK
Pharmacokinetic(s)
PPI
Proton pump inhibitor
PT
Prothrombin time 
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
SIR-I
Steroid Inadequate Responders/Intolerant
SMT
Safety Management Team
SOP
Standard operating procedure
SUSARs
Suspected unexpected serious adverse reactions
t½
Terminal elimination half-life
TB
Tuberculosis
TEAE
Treatment-emergent adverse event
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Table 9:
Abbreviations and Specialist Terms
Abbreviation or Specialist Term
Explanation
tmax
Time to the observed maximum concentration 
TNF
Tumor necrosis factor alpha
ULN
Upper limit of normal
US
United States
WBC
White blood cell
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APPENDIX B
MODIFIED DAILY SYMPTOM DIARY (MDSD)
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