A Study to Evaluate the Efficacy and Safety of CC-93538 in Adult and Adolescent Participants With Eosinophilic Esophagitis

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

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

Study Overview

• Status: Completed
• Conditions: Eosinophilic Esophagitis
• Intervention / Treatment: Drug: CC-93538; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 430
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1199ABB
    • Local Institution - 697
  • Mar Del Plata, Argentina, B7600DHK
    • Local Institution - 695
  • Quilmes, Argentina, B1878DVB
    • Local Institution - 696
• Australia
  • Fitzroy, Australia, 3065
    • Local Institution - 538
  • Western Australia, Australia, 6056
    • Local Institution - 547
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Local Institution - 548
    • Liverpool, New South Wales, Australia, 2170
      • Local Institution - 554
    • Westmead, New South Wales, Australia, 2145
      • Local Institution - 540
  • Queensland
    • Maroorchydore, Queensland, Australia, 4558
      • Local Institution - 546
    • South Brisbane, Queensland, Australia, 4101
      • Local Institution - 550
    • Woolloongabba, Queensland, Australia, 4102
      • Local Institution - 542
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Local Institution - 552
    • Elizabeth Vale, South Australia, Australia, 05112
      • Local Institution - 545
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Local Institution - 553
    • Footscray, Victoria, Australia, 3011
      • Local Institution - 543
    • Melbourne, Victoria, Australia, 3004
      • Local Institution - 539
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Local Institution - 549
• Austria
  • Burgenland, Austria, 7000
    • Local Institution - 437
  • Graz, Austria, 8036
    • Local Institution - 434
  • Linz, Austria, 4010
    • Local Institution - 436
• Belgium
  • Brussels, Belgium, 1090
    • Local Institution - 515
  • Kortrijk, Belgium, 8500
    • Local Institution - 516
  • Leuven, Belgium, 3000
    • Local Institution - 514
  • West-Vlaanderen, Belgium, 8310
    • Local Institution - 512
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Local Institution - 201
    • Edmonton, Alberta, Canada, T5R 1W2
      • Local Institution - 208
    • Edmonton, Alberta, Canada, T6K 4B2
      • Local Institution - 205
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • Local Institution - 203
    • Victoria, British Columbia, Canada, V8V3M9
      • Local Institution - 206
  • Ontario
    • Ottawa, Ontario, Canada, K1H 1E4
      • Local Institution - 207
    • Vaughan, Ontario, Canada, L4L 4Y7
      • Local Institution - 200
• Germany
  • Bayern, Germany, 82418
    • Local Institution - 330
  • Brandenburg an der Havel, Germany, 14770
    • Local Institution - 332
  • Frankfurt am Main, Germany, 60313
    • Local Institution - 339
  • Hamburg, Germany, 20249
    • Local Institution - 336
  • Leipzig, Germany, 04103
    • Local Institution - 333
  • Leipzig, Germany, 04129
    • Local Institution - 338
  • Munchen, Germany, 81675
    • Local Institution - 337
  • München, Germany, 80639
    • Local Institution - 340
• Israel
  • Haifa, Israel, 3109601
    • Local Institution - 281
  • Holon, Israel, 5822012
    • Local Institution - 283
  • Jerusalem, Israel, 91031
    • Local Institution - 280
  • Jerusalem, Israel, 91120
    • Local Institution - 282
  • Tel Aviv, Israel, 64239
    • Local Institution - 278
  • Zerifin, Israel, 70300
    • Local Institution - 279
• Italy
  • Genova, Italy, 16132
    • Local Institution - 257
  • Milano, Italy, 20122
    • Local Institution - 254
  • Padova, Italy, 35128
    • Local Institution - 255
  • Pisa, Italy, 56100
    • Local Institution - 252
  • Rome, Italy, 00161
    • Local Institution - 253
• Japan
  • Akita-shi, Japan, 010-8543
    • Local Institution - 593
  • Isehara City, Kanagawa, Japan, 259-1193
    • Local Institution - 606
  • Kobe, Japan, 650-0017
    • Local Institution - 597
  • Maebashi, Japan, 371-8511
    • Local Institution - 598
  • Nagoya, Japan, 457-8511
    • Local Institution - 604
  • Nagoya, Japan, 467-8602
    • Local Institution - 607
  • Niigata-shi, Japan, 951-8510
    • Local Institution - 592
  • Okayama-Shi, Japan, 700-8505
    • Local Institution - 603
  • Osaka, Japan, 545-8586
    • Local Institution - 591
  • Shibukawa, Japan, 377-8577
    • Local Institution - 601
  • Shinjuku-Ku, Japan, 162-8655
    • Local Institution - 602
  • Tokyo, Japan, 108-8329
    • Local Institution - 605
  • Toyoake, Japan, 470-1192
    • Local Institution - 596
  • Yamagata, Japan, 990-9585
    • Local Institution - 590
  • Hyogo
    • Nishinomiya, Hyogo, Japan, 663-8501
      • Local Institution - 600
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8603
      • Local Institution - 595
    • Setagaya-ku, Tokyo, Japan, 157-8535
      • Local Institution - 599
• Poland
  • Bydgoszcz, Poland, 85-079
    • Local Institution - 385
  • Częstochowa, Poland, 42-202
    • Local Institution - 389
  • Gdansk, Poland, 80-382
    • Local Institution - 390
  • Katowice, Poland, 40-040
    • Local Institution - 388
  • Lódz, Poland, 90-127
    • Local Institution - 392
  • Warsaw, Poland, 04-501
    • Local Institution - 383
  • Warszawa, Poland, 01-192
    • Local Institution - 393
  • Warszawa, Poland, 00-189
    • Local Institution - 387
  • Wroclaw, Poland, 50-556
    • Local Institution - 386
  • Wroclaw, Poland, 51-162
    • Local Institution - 384
  • Wrocław, Poland, 50-381
    • Local Institution - 391
• Portugal
  • Lisboa, Portugal, 1169-045
    • Local Institution - 307
  • Lisboa, Portugal, 1649-035
    • Local Institution - 305
  • Porto, Portugal, 4099-001
    • Local Institution - 306
  • Porto, Portugal, 4200-319
    • Local Institution - 308
• Spain
  • Barcelona, Spain, 08036
    • Local Institution - 408
  • Cordoba, Spain, 14001
    • Local Institution - 410
  • Madrid, Spain, 28006
    • Local Institution - 409
  • Madrid, Spain, 28046
    • Local Institution - 413
  • Marbella, Spain, 29603
    • Local Institution - 411
  • Sevilla, Spain, 41013
    • Local Institution - 412
• Switzerland
  • Lausanne, Switzerland, 1011
    • Local Institution - 357
• United Kingdom
  • Belfast Northern Ireland, United Kingdom, BT9 7AB
    • Local Institution - 228
  • Birmingham, United Kingdom, B15 2SQ
    • Local Institution - 231
  • Cardiff, United Kingdom, CF15 9SS
    • Local Institution - 234
  • Chorley, United Kingdom, PR7 7NA
    • Local Institution - 235
  • Hexam, United Kingdom, NE46 1QJ
    • Local Institution - 233
  • Liverpool, United Kingdom, L22 0LG
    • Local Institution - 236
  • Manchester, United Kingdom, M15 6SX
    • Local Institution - 237
  • Southampton, United Kingdom, SO16 6YD
    • Local Institution - 226
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211-1320
      • Local Institution - 144
    • Tuscaloosa, Alabama, United States, 35406
      • Local Institution - 158
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Local Institution - 082
    • Phoenix, Arizona, United States, 85020-4348
      • Local Institution - 147
    • Scottsdale, Arizona, United States, 85259
      • Local Institution - 041
    • Tucson, Arizona, United States, 85715
      • Local Institution - 029
  • Arkansas
    • North Little Rock, Arkansas, United States, 72117
      • Local Institution - 165
  • California
    • Lancaster, California, United States, 93534
      • Local Institution - 075
    • Los Angeles, California, United States, 90067
      • Local Institution - 047
    • Oakland, California, United States, 94609
      • Local Institution - 084
    • San Diego, California, United States, 92103-5639
      • Local Institution - 160
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Local Institution - 068
    • Colorado Springs, Colorado, United States, 80907
      • Local Institution - 067
    • Denver, Colorado, United States, 80218
      • Local Institution - 092
    • Littleton, Colorado, United States, 80120-5641
      • Local Institution - 170
    • Wheat Ridge, Colorado, United States, 80033
      • Local Institution - 128
  • Connecticut
    • Bristol, Connecticut, United States, 06010
      • Local Institution - 101
    • Farmington, Connecticut, United States, 06030
      • Local Institution - 076
    • Hamden, Connecticut, United States, 06518
      • Local Institution - 156
  • Florida
    • Clearwater, Florida, United States, 33756-3839
      • Local Institution - 099
    • Inverness, Florida, United States, 34452
      • Local Institution - 036
    • Jacksonville, Florida, United States, 32256
      • Local Institution - 042
    • Miami, Florida, United States, 33032
      • Local Institution - 161
    • Miami, Florida, United States, 33144-2035
      • Local Institution - 138
    • North Miami Beach, Florida, United States, 33162
      • Local Institution - 110
    • Orlando, Florida, United States, 32806-1041
      • Local Institution - 146
    • Orlando, Florida, United States, 32806
      • Local Institution - 088
    • Orlando, Florida, United States, 32825
      • Local Institution - 133
    • Pinellas Park, Florida, United States, 33781-3228
      • Local Institution - 169
    • Plantation, Florida, United States, 33324-3345
      • Local Institution - 168
    • Port Orange, Florida, United States, 32127
      • Local Institution - 037
    • Sweetwater, Florida, United States, 33172-2741
      • Local Institution - 140
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Local Institution - 043
    • Atlanta, Georgia, United States, 30328
      • Local Institution - 171
    • Atlanta, Georgia, United States, 30342
      • Local Institution - 054
    • Macon, Georgia, United States, 31201
      • Local Institution - 117
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Local Institution - 024
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Local Institution - 039
    • Gurnee, Illinois, United States, 60031-5711
      • Local Institution - 167
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Local Institution - 118
  • Iowa
    • Clive, Iowa, United States, 50325
      • Local Institution - 127
    • Iowa City, Iowa, United States, 52242
      • Local Institution - 094
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Local Institution - 035
  • Kentucky
    • Florence, Kentucky, United States, 41042
      • Local Institution - 046
    • Louisville, Kentucky, United States, 40202
      • Local Institution - 019
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Local Institution - 003
    • Metairie, Louisiana, United States, 70006
      • Local Institution - 020
    • Metairie, Louisiana, United States, 70006
      • Local Institution - 044
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Local Institution - 109
    • Catonsville, Maryland, United States, 21228
      • Local Institution - 065
    • Columbia, Maryland, United States, 21045
      • Local Institution - 164
    • Glen Burnie, Maryland, United States, 21061
      • Local Institution - 070
    • Hagerstown, Maryland, United States, 21742
      • Local Institution - 012
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Local Institution - 097
    • Boston, Massachusetts, United States, 02111
      • Local Institution - 053
    • Framingham, Massachusetts, United States, 01702
      • Local Institution - 017
    • South Dartmouth, Massachusetts, United States, 02747
      • Local Institution - 083
    • Springfield, Massachusetts, United States, 01199
      • Local Institution - 081
    • Worcester, Massachusetts, United States, 01655
      • Local Institution - 009
  • Michigan
    • Troy, Michigan, United States, 48098
      • Local Institution - 098
    • Wyoming, Michigan, United States, 49519
      • Local Institution - 014
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Local Institution - 115
    • Rochester, Minnesota, United States, 55905
      • Local Institution - 049
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Local Institution - 034
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Local Institution - 007
    • Saint Louis, Missouri, United States, 63110-1010
      • Local Institution - 032
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Local Institution - 038
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Local Institution - 015
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106-4725
      • Local Institution - 139
  • New York
    • Great Neck, New York, United States, 11023
      • Local Institution - 028
    • New York, New York, United States, 10017-2009
      • Local Institution - 154
    • New York, New York, United States, 10029
      • Local Institution - 011
    • New York, New York, United States, 10016-4744
      • Local Institution - 051
    • Syracuse, New York, United States, 13210-2306
      • Local Institution - 116
    • Syracuse, New York, United States, 13210
      • Local Institution - 142
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Local Institution - 016
    • Charlotte, North Carolina, United States, 28277
      • Local Institution - 045
    • Durham, North Carolina, United States, 27705
      • Local Institution - 106
    • Greensboro, North Carolina, United States, 27405-6950
      • Local Institution - 131
    • Kinston, North Carolina, United States, 28501-3851
      • Local Institution - 126
  • Ohio
    • Beavercreek, Ohio, United States, 45440-3237
      • Local Institution - 130
    • Cincinnati, Ohio, United States, 45219
      • Local Institution - 006
    • Cincinnati, Ohio, United States, 45229
      • Local Institution - 001
    • Cincinnati, Ohio, United States, 45267
      • Local Institution - 052
    • Cleveland, Ohio, United States, 44195
      • Local Institution - 072
    • Columbus, Ohio, United States, 43212-3119
      • Local Institution - 145
    • Columbus, Ohio, United States, 43235
      • Local Institution - 059
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112-5550
      • Local Institution - 166
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Local Institution - 120
    • Philadelphia, Pennsylvania, United States, 19104
      • Local Institution - 025
    • Pottsville, Pennsylvania, United States, 17901-3636
      • Local Institution - 155
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Local Institution - 066
  • South Carolina
    • Anderson, South Carolina, United States, 29621-2062
      • Local Institution - 143
    • Greenville, South Carolina, United States, 29615
      • Local Institution - 057
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Local Institution - 114
    • Nashville, Tennessee, United States, 37212
      • Local Institution - 095
  • Texas
    • Cedar Park, Texas, United States, 78613
      • Local Institution - 105
    • Dallas, Texas, United States, 75234-7858
      • Local Institution - 148
    • Houston, Texas, United States, 77079-2211
      • Local Institution - 112
    • Rockwell, Texas, United States, 75032
      • Local Institution - 079
    • San Antonio, Texas, United States, 78229
      • Local Institution - 008
    • Southlake, Texas, United States, 76092
      • Local Institution - 077
    • Tyler, Texas, United States, 75701
      • Local Institution - 104
  • Utah
    • Draper, Utah, United States, 84020-5645
      • Local Institution - 157
    • Ogden, Utah, United States, 84403-3323
      • Local Institution - 125
    • Salt Lake City, Utah, United States, 84132
      • Local Institution - 074
  • Virginia
    • Leesburg, Virginia, United States, 20176
      • Local Institution - 027
    • Lynchburg, Virginia, United States, 24502
      • Local Institution - 013
    • Richmond, Virginia, United States, 23249
      • Local Institution - 064
    • Roanoke, Virginia, United States, 24013
      • Local Institution - 134
  • Washington
    • Spokane, Washington, United States, 99218
      • Local Institution - 137
    • Vancouver, Washington, United States, 98664
      • Local Institution - 023
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Local Institution - 085
    • Milwaukee, Wisconsin, United States, 53226
      • Local Institution - 060
  • Wyoming
    • Casper, Wyoming, United States, 10456
      • Local Institution - 121

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants must satisfy the following criteria to be enrolled in the study:

1. Male or female patients aged ≥ 12 and ≤ 75 years, with a body weight of > 40 kg.
2. Histologic evidence of eosinophilic esophagitis, defined as a peak count of ≥ 15 eosinophils/high-power field at 2 levels of the esophagus.

3 Participant-reported history of 4 or more Dysphagia Days within 2 consecutive weeks prior to end of screening.

4. Lack of complete response to an adequate trial of proton pump inhibitor (8 weeks). Participants on a proton pump inhibitor must have been on a stable dose for at least 4 weeks prior to first Screening Visit and agree to continue the same dose throughout the study.

5. Participants currently receiving inhaled corticosteroids, leukotriene receptor antagonists, or mast cell stabilizers for indications other than EoE, or medium potency topical corticosteroids for dermatologic conditions, must maintain stable doses for at least 4 weeks prior to the first Screening Visit and throughout the duration of the study.

6. Participants must agree to maintain a stable diet (including any food elimination diet for the treatment of food allergy or eosinophilic esophagitis) and not introduce any changes in their diet from the first Screening Visit to the end of the study.

7. Females of childbearing potential must have 2 negative pregnancy tests as verified by the Investigator prior to starting study therapy and agree to practice a highly effective method of contraception until 5 months after the last dose.

Exclusion Criteria:

The presence of any of the following will exclude a participant from enrollment:

1. Clinical or endoscopic evidence of other diseases that may affect the histologic, endoscopic, and clinical symptom evaluation for this study.
2. Other gastrointestinal disorders such as active Helicobacter pylori infection, esophageal varices, gastritis, colitis, celiac disease, Mendelian disorder associated with eosinophilic esophagitis, liver function impairment, or a known hereditary fructose intolerance.
3. Evidence of a severe endoscopic structural abnormality in the esophagus.
4. Esophageal dilation for symptom relief within 8 weeks prior to first Screening Visit or during the Screening Period, or if esophageal dilation is anticipated within 48 weeks of dosing during the study.
5. Evidence of immunosuppression, or of having received systemic immunosuppressive or immunomodulating drugs within 5 drug half-lives prior to the first Screening Visit.
6. Treatment with a high potency topical corticosteroid for dermatologic use, or a systemic corticosteroid within 8 weeks of the first Screening Visit.
7. Treatment with a swallowed topical corticosteroid, leukotriene receptor antagonist, or mast cell stabilizer for EoE, within 4 weeks of the first Screening Visit.
8. Treatment with oral or sublingual immunotherapy within 6 months of the first Screening Visit (any use will be prohibited during the study). Subcutaneous immunotherapy may be allowed if on stable doses for at least 3 months prior to the first Screening Visit and during the study.
9. Actively successful dietary modification adherence (e.g. food elimination diet), resulting in a complete response to EoE.
10. Prior treatment with CC-93538 during a Phase 1 or 2 clinical study.
11. Receipt of a live attenuated vaccine within 4 weeks of the first Screening Visit.
12. Any disease that would affect the conduct of the protocol or interpretation of the study results, or would put a patient at risk by participating in the study (e.g. severe uncontrolled asthma, infection causing eosinophilia, hypereosinophilic syndrome, or cardiovascular condition, or neurologic disorder or psychiatric illness that compromises the Participant's ability to accurately document symptoms of eosinophilic esophagitis).
13. Active or ongoing infections including parasitic/helminthic, hepatitis, tuberculosis, or human immunodeficiency virus.
14. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 4 weeks of the first Screening Visit.
15. Females who are pregnant or lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Administration of CC-93538; CC-93538 360 mg Subcutaneously (SC) once weekly for 24 weeks followed by CC-93538 360 mg SC once weekly for 24 weeks	Drug: CC-93538; Subcutaneous; Other Names: RPC4046
Experimental: Administration of CC-93538 and Placebo; 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.	Drug: CC-93538; Subcutaneous; Other Names: RPC4046; Other: Placebo; Subcutaneous
Placebo Comparator: Administration of Placebo; Matching placebo SC once weekly for 24 weeks followed by matching placebo SC once weekly for 24 weeks	Other: Placebo; Subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Dysphagia Days (DD) at Week 24	Dysphagia Days (DD) was assessed using a modified daily symptom diary (mDSD). The DD was evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The number of DD was normalized by calculating the number of diary days with a "yes" to any or all of Q2, Q3, and Q4 in the 14-day period prior to a visit, dividing by the number of measurable diary days in the 14-day period, and then multiplying by the length of the period (14). A measurable diary day for DD is defined as a diary day for which Questions 2 to 4 are answered. Mean DD ranges from 0 to 14 for the 14-day period.	Baseline (Day 1) and Week 24
Percentage of Participants With Peak Esophageal Eosinophil Count <= 6/High-power Field (Hpf) at Week 24	Blood samples were collected to assess esophageal eosinophil count.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Peak Esophageal Eosinophil Count <= 6/High-power Field (Hpf) at Week 48	Blood samples were collected to assess esophageal eosinophil count.	Week 48
Percentage of Participants With Peak Esophageal Eosinophil Count < 15/High-power Field (Hpf) at Week 24	Blood samples were collected to assess esophageal eosinophil count.	Week 24
Percentage of Participants With Peak Esophageal Eosinophil Count < 15/High-power Field (Hpf) at Week 48	Blood samples were collected to assess esophageal eosinophil count.	Week 48
Change From Baseline in Mean Dysphagia Days (DD) at Week 48	Dysphagia Days (DD) was assessed using a modified daily symptom diary (mDSD). The DD was evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The number of DD was normalized by calculating the number of diary days with a "yes" to any or all of Q2, Q3, and Q4 in the 14-day period prior to a visit, dividing by the number of measurable diary days in the 14-day period, and then multiplying by the length of the period (14). A measurable diary day for DD is defined as a diary day for which Questions 2 to 4 are answered. Mean DD ranges from 0 to 14 for the 14-day period.	Baseline (Day 1) and Week 48
Change From Baseline in Eosinophilic Esophagitis (EoE) Endoscopic Reference Score (EREFS) at Week 24	The EREFS, measures features of EoE including esophageal edema, fixed rings, exudates, furrows, and strictures. The instrument grades edema as none (0) or present (1) or severe; furrows as absent (0), present (1); rings as none (0), mild (1), moderate (2) and severe (3); exudates as none (0), mild (1) or severe (2); and strictures as absent (0) or present (1). Two sub-component scores will be calculated by adding up the grade from respective features across the 3 esophagus levels (proximal, mid, and distal). Inflammation composite score (ranging 0 to 12) includes edema, furrows and exudates while remodeling composite score (0 to 12) consist of stricture and fixed rings. The EREFS total score is the sum of the inflammation and remodeling composite scores. The EREFS total score ranges from 0 to 24. High score signifies severe condition.	Baseline (Day 1) , Week 24
Change From Baseline in Eosinophilic Esophagitis (EoE) Endoscopic Reference Score (EREFS) at Week 48	The EREFS, measures features of EoE including esophageal edema, fixed rings, exudates, furrows, and strictures. The instrument grades edema as none (0) or present (1) or severe; furrows as absent (0), present (1); rings as none (0), mild (1), moderate (2) and severe (3); exudates as none (0), mild (1) or severe (2); and strictures as absent (0) or present (1). Two sub-component scores will be calculated by adding up the grade from respective features across the 3 esophagus levels (proximal, mid, and distal). Inflammation composite score (ranging 0 to 12) includes edema, furrows and exudates while remodeling composite score (0 to 12) consist of stricture and fixed rings. The EREFS total score is the sum of the inflammation and remodeling composite scores. The EREFS total score ranges from 0 to 24. High score signifies severe condition.	Baseline (Day 1) , Week 48
Change From Baseline in Mean Adjusted Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Grade Score at Week 24	EoEHSS evaluates the grade (severity) of multiple pathologic features in esophageal biopsies. It has 8 features eosinophil inflammation, basal zone hyperplasia, eosinophil abscess, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. In 3 separate esophagus levels (proximal, mid, and distal), each feature is scored independently for grade using a 4-point Likert scale (0 [absent] to 3 [severe]). The mean adjusted grade score is calculated by averaging the adjusted scores for the 3 levels (proximal, mid, and distal). The mean adjusted scores range from 0 to 100. High score signifies severe condition.	Baseline (Day 1), Week 24
Change From Baseline in Mean Adjusted Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Grade Score at Week 48	EoEHSS evaluates the grade (severity) of multiple pathologic features in esophageal biopsies. It has 8 features eosinophil inflammation, basal zone hyperplasia, eosinophil abscess, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. In 3 separate esophagus levels (proximal, mid, and distal), each feature is scored independently for grade using a 4-point Likert scale (0 [absent] to 3 [severe]). The mean adjusted grade score is calculated by averaging the adjusted scores for the 3 levels (proximal, mid, and distal). The mean adjusted scores range from 0 to 100. High score signifies severe condition.	Baseline (Day 1) , Week 48
Change From Baseline in Mean Adjusted Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Stage Score at Week 24	EoEHSS evaluates the stage (extent) of multiple pathologic features in esophageal biopsies. It has 8 features eosinophil inflammation (determined by peak EoS count(PEC)) and presence of basal zone hyperplasia, eosinophil abscess, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis in epithelium . In 3 separate esophagus levels (proximal, mid, and distal), each feature is scored independently for stage using a 4-point Likert scale (0 [absent], 1[PEC ≥15/hpf in <33% of hpfs or (any grade >0) <33% of epithelium for other features], 2 [PEC ≥15/hpf in 33-66% of hpfs or (any grade >0) in 33-66% of epithelium to 3 [PEC ≥15/hpf in >66% of hpfs or (any grade >0) in > 66% of epithelium]). The mean adjusted stage score is calculated by averaging the adjusted scores for the 3 levels (proximal, mid, and distal). The mean adjusted scores range from 0 to 100. High score signifies severe condition.	Baseline (Day 1), Week 24
Change From Baseline in Mean Adjusted Eosinophilic Esophagitis Histology Scoring System (EoEHSS) Stage Score at Week 48	EoEHSS evaluates the stage (extent) of multiple pathologic features in esophageal biopsies. It has 8 features eosinophil inflammation (determined by peak EoS count(PEC)) and presence of basal zone hyperplasia, eosinophil abscess, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis in epithelium . In 3 separate esophagus levels (proximal, mid, and distal), each feature is scored independently for stage using a 4-point Likert scale (0 [absent], 1[PEC ≥15/hpf in <33% of hpfs or (any grade >0) <33% of epithelium for other features], 2 [PEC ≥15/hpf in 33-66% of hpfs or (any grade >0) in 33-66% of epithelium to 3 [PEC ≥15/hpf in >66% of hpfs or (any grade >0) in > 66% of epithelium]). The mean adjusted stage score is calculated by averaging the adjusted scores for the 3 levels (proximal, mid, and distal). The mean adjusted scores range from 0 to 100. High score signifies severe condition.	Baseline (Day 1) , Week 48
Change From Baseline in Modified Daily Symptom Diary (mDSD) Composite Score at Week 24	The mDSD composite score is evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The daily symptom score (mDSD) is calculated by summing the responses to Q2, Q3, and Q4 (where "Yes" to any/all items equals 1, and "No" to all items equals 0), adding Q5 over the 14-day period prior to a visit, dividing by the number of measurable diary days over the 14-day period, and then multiplying by the length of the period (14). The daily symptom score ranges from 0 to 5, and the mDSD composite score ranges from 0 to 70 for the 14-day period. A higher composite diary score indicates more frequent and/or severe dysphagia symptoms.	Baseline (11 days prior to Day 1) and Week 24
Change From Baseline in Modified Daily Symptom Diary (mDSD) Composite Score at Week 48	The mDSD composite score is evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The daily symptom score (mDSD) is calculated by summing the responses to Q2, Q3, and Q4 (where "Yes" to any/all items equals 1, and "No" to all items equals 0), adding Q5 over the 14-day period prior to a visit, dividing by the number of measurable diary days over the 14-day period, and then multiplying by the length of the period (14). The daily symptom score ranges from 0 to 5, and the mDSD composite score ranges from 0 to 70 for the 14-day period. A higher composite diary score indicates more frequent and/or severe dysphagia symptoms.	Baseline (Day 1) , Week 48
Percentage of Participants With a ≥ 50% Decrease in Dysphagia Days(DD) From Baseline at Week 24	Dysphagia Days (DD) was assessed using a modified daily symptom diary (mDSD). The DD was evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The number of DD was normalized by calculating the number of diary days with a "yes" to any or all of Q2, Q3, and Q4 in the 14-day period prior to a visit, dividing by the number of measurable diary days in the 14-day period, and then multiplying by the length of the period (14). A measurable diary day for DD is defined as a diary day for which Questions 2 to 4 are answered. DD ranges from 0 to 14 for the 14-day period.	Baseline (11 days prior to Day 1) and Week 24
Percentage of Participants With a ≥ 50% Decrease in Dysphagia Days(DD) From Baseline at Week 48	Dysphagia Days (DD) was assessed using a modified daily symptom diary (mDSD). The DD was evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The number of DD was normalized by calculating the number of diary days with a "yes" to any or all of Q2, Q3, and Q4 in the 14-day period prior to a visit, dividing by the number of measurable diary days in the 14-day period, and then multiplying by the length of the period (14). A measurable diary day for DD is defined as a diary day for which Questions 2 to 4 are answered. DD ranges from 0 to 14 for the 14-day period.	Baseline (11 days prior to Day 1) and Week 48
Change From Baseline in Mean Dysphagia Days (DD) Through Week 24	Dysphagia Days (DD) was assessed using a modified daily symptom diary (mDSD). The DD was evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The number of DD was normalized by calculating the number of diary days with a "yes" to any or all of Q2, Q3, and Q4 in the 14-day period prior to a visit, dividing by the number of measurable diary days in the 14-day period, and then multiplying by the length of the period (14). A measurable diary day for DD is defined as a diary day for which Questions 2 to 4 are answered. Mean DD ranges from 0 to 14 for the 14-day period.	Baseline (Day 1), Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
Change From Baseline in Modified Daily Symptom Diary (mDSD) Composite Score Through Week 24	The mDSD composite score is evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The daily symptom score (mDSD) is calculated by summing the responses to Q2, Q3, and Q4 (where "Yes" to any/all items equals 1, and "No" to all items equals 0), adding Q5 over the 14-day period prior to a visit, dividing by the number of measurable diary days over the 14-day period, and then multiplying by the length of the period (14). The daily symptom score ranges from 0 to 5, and the mDSD composite score ranges from 0 to 70 for the 14-day period. A higher composite diary score indicates more frequent and/or severe dysphagia symptoms.	Baseline (11 days prior to Day 1) and Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
Time to First Event of Eosinophilic Esophagitis (EoE) Flare	First incidence of corresponding EoE flare event for any participant was considered in the analysis. Median and 95% CI are from Kaplan-Meier estimates. Participants without an event of EoE flare or discontinued the study by the end of maintenance phase were censored, if they are a dropout, they are censored at study discontinuation date, otherwise they are censored at either last dose date or last visit, whichever was longer.	From first dose (Day 1) and Up to Week 48
Time to First Use of Rescue Medication	First use of rescue therapy including EoE standard of care pharmacotherapy, dietary modification (e.g., food elimination diet), and/or dilation procedure. was considered in the analysis. Median and 95% CI are from Kaplan-Meier estimates. Participants without an event or discontinued the study by the end of maintenance phase were censored, if they are a dropout, they are censored at study discontinuation date, otherwise they are censored at either last dose date or last visit, whichever was longer.	From first dose (Day 1) and Up to Week 48
Percentage of Participants With Any Events of Use of Rescue Medication	Use of rescue therapy including EoE standard of care pharmacotherapy, dietary modification (e.g., food elimination diet), and/or dilation procedure was considered in the analysis.	From first dose (Day 1) and up to Week 48
Percentage of Participants With Eosinophilic Esophagitis (EoE) Flare	First incidence of corresponding EoE flare event for any participant was considered in the analysis.	From first dose (Day 1) and up to Week 48
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization.	From first dose (Day 1) till up to Week 48
Number of Participants With Maximum Post-Baseline Clinical Laboratory Range Shift	Blood samples were collected to assess clinical laboratory parameters. The row title contains parameter and category title contains shift. The category 'Normal to High' signifies the readings for the parameter were 'Normal' at baseline and it changed to 'High' post baseline.	From first dose (Day 1) till up to Week 48
Number of Participants With Post-Baseline Vital Sign Abnormalities	Vital signs like feart rate (beats per minute) and systolic blood pressure (mmHg) and diastolic blood pressure (mmHg) was measured to assess the abnormalities.	From first dose (Day 1) till up to Week 48
Change From Baseline in Physical Parameters - Height at Week 24	Height was measured at specified timepoints to assess the change from baseline.	Baseline (Day 1) and Week 24
Change From Baseline in Physical Parameters - Height at Week 48	Height was measured at specified timepoints to assess the change from baseline.	Baseline (Day 1) and Week 48
Change From Baseline in Physical Parameters - Weight at Week 24	Weight was measured at specified timepoints to assess the change from baseline.	Baseline (Day 1) and Week 24
Change From Baseline in Physical Parameters - Weight at Week 48	Weight was measured at specified timepoints to assess the change from baseline.	Baseline (Day 1) and Week 48
Change From Baseline in Physical Parameters - Body Mass Index at Week 24	Data was collected for height and weight to assess body mass index.	Baseline (Day 1) and Week 24
Change From Baseline in Physical Parameters - Body Mass Index at Week 48	Data was collected for height and weight to assess body mass index.	Baseline (Day 1) and Week 48
Number of Participants With Anti-Drug Antibodies (ADA)	ADA status were categorized as Baseline ADA Positive: Pre-existing Immunoreactivity (baseline positive and 1) post baseline negative or 2) titer < 4-fold baseline titer). NAb+/baseline ADA+: At least one ADA positive sample with positive NAb in participant with pre-existing immunoreactivity. ADA Positive Status: 1) at least one positive response post first dose given negative or missing baseline; or 2) at least one post-baseline with titer greater than or equal to 4-fold of baseline titer given positive baseline. NAb+/ADA+: At least one ADA positive sample with positive NAb in ADA positive participant.	Pre-dose Week 24 and Pre-dose Week 48
Serum Trough Concentration of CC-93538 at Week 24 and Week 48	Blood samples were collected to assess trough concentration of CC-93538. The Evaluable PK population is defined as all participants in the PK population who have at least one evaluable trough concentration.	Pre-dose Week 24 and Pre-dose Week 48

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2021
• Primary Completion (Actual): January 11, 2024
• Study Completion (Actual): August 29, 2024

Study Registration Dates

• First Submitted: February 5, 2021
• First Submitted That Met QC Criteria: February 11, 2021
• First Posted (Actual): February 15, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 24, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Adolescent; Hypersensitivity; Gastroenteritis; Gastrointestinal Diseases; Adult; Esophagitis; Eosinophilic Esophagitis; CC-93538; RPC4046; Eosinophils; Eosinophilia; Esophageal Diseases; Allergic Diseases; Antibody, Monoclonal; Immunologic factors; Physiological Effects of Drugs; cendakimab
• Additional Relevant MeSH Terms: Immune System Diseases; Digestive System Diseases; Gastrointestinal Diseases; Hypersensitivity, Immediate; Hypersensitivity; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Esophageal Diseases; Gastroenteritis; Esophagitis; Eosinophilic Esophagitis
• Other Study ID Numbers: CC-93538-EE-001; U1111-1263-4351 (Registry Identifier: WHO); 2020-004336-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No