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

Phase 3

Active, not recruiting

Conditions: Eosinophilic Gastroenteritis

Interventions: Drug: Placebo
Drug: CC-93538

Registration Number: NCT05214768

Lead Sponsor: Celgene

Brief Summary: The purpose of this study is to evaluate the safety and efficacy of CC-93538 in adult and adolescent participants with eosinophilic gastroenteritis.

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 48

Inclusion Criteria

Histologic evidence of eosinophilic gastroenteritis (EGE) defined as ≥ 30 eosinophils (eos)/high-power field (hpf) in at least 5 hpf in the stomach and/or ≥ 30 eos/hpf in at least 3 hpf in the duodenum while on stable background therapy for EGE
Has weekly symptom scores of ≥ 4/15 for any of Gastric Pain Symptoms domain, Stomach Heaviness Symptom domains, and /or Diarrhea Symptoms domain as assessed by the Izumo Scale with electronic device for the 2 consecutive weeks before Day 1
Must agree to maintain a stable diet from the first Screening Visit and throughout the duration of the study, and participants must have maintained a stable diet for at least 4 weeks prior to the first Screening Visit
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

Ascites requiring treatment or symptomatic ascites
History of inflammatory bowel disease, achalasia or esophageal surgery
Has other causes of gastric and/or duodenal eosinophilia or eosinophilic granulomatosis with polyangiitis (EGPA)

Other protocol-defined inclusion/exclusion criteria apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
CC-93538	CC-93538	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Number of Peak Eosinophils (Eos) Count Per High-power Field (Hpf) in Gastrointestinal (GI) Biopsies	Baseline and Week 16	Blood samples were collected to assess eosinophils count. Baseline data are defined as last measurement collected on or prior the date of first dose for Induction Phase.

Secondary Outcome Measures

Name	Time	Method
Induction Phase: Changes in Each of 5 Domain Scores of the Izumo Scale From Baseline at Week 16	Baseline and Week 16	The Izumo Scale questionnaire assesses the comprehensive 5 different GI symptom domains during the past week and consists with 15 weekly questions (3 questions per 1 domain): Heartburn Symptoms domain(Questions1 through3), Gastric Pain Symptoms domain(Questions4 through6), Stomach Heaviness Symptoms domain(Questions7 through9), Constipation Symptoms domain (Question 10 through12), Diarrhea Symptoms domain (Questions13 through15). Each question is scored on a 6-point Likert scale of "0 = No trouble at all" to "5 = Can't stand it," and the score for each question within a domain is added to determine domain specific scores scaled from 0 to 15, with higher values indicating greater symptom severity.
Induction + Maintenance: Changes in Each of 5 Domain Scores of the Izumo Scale From Baseline at Week 48	Baseline and Week 48	The Izumo Scale questionnaire assesses the comprehensive 5 different GI symptom domains during the past week and consists with 15 weekly questions (3 questions per 1 domain): Heartburn Symptoms domain(Questions1 through3), Gastric Pain Symptoms domain(Questions4 through6), Stomach Heaviness Symptoms domain(Questions7 through9), Constipation Symptoms domain (Question 10 through12), Diarrhea Symptoms domain (Questions13 through15). Each question is scored on a 6-point Likert scale of "0 = No trouble at all" to "5 = Can't stand it," and the score for each question within a domain is added to determine domain specific scores scaled from 0 to 15, with higher values indicating greater symptom severity. Participants that discontinued Induction period without entering maintenance period are included in the CC-93538 360 mg QW arm.
Induction Phase: Percentage of Participants Who Achieve Both Clinical and Histologic Response Composite at Week 16	Week 16	Clinical response defined as percentage of participants who achieve \<4/15 in each of three Symptoms of Interest (Gastric Pain Symptoms domain, Stomach Heaviness Symptoms domain, and Diarrhea Symptoms domain) scores of Izumo Scale from baseline. Histologic response defined as a \> 75% reduction of peak gastric and/or duodenal eos count from baseline. Izumo Scale tests 5 different GI symptom domains during past week and consists with 15 weekly questions (3 questions per 1 domain): Heartburn Symptoms domain(Ques1 through3), Gastric Pain Symptoms domain(Questions4 through6), Stomach Heaviness Symptoms domain(Ques7 through9), Constipation Symptoms domain (Question 10 through12), Diarrhea Symptoms domain (Ques13 through15). Each question is scored on a 6-point Likert scale of "0 = No trouble at all" to "5 = Can't stand it," and score for each question within a domain added to determine domain specific scores scaled from 0 to 15, with higher values indicating greater symptom severity.
Induction + Maintenance: Percentage of Participants Who Achieve Both Clinical and Histologic Response Composite at Week 48	Baseline and week 48	Clinical response defined as percentage of participants who achieve \<4/15 in each of three Symptoms of Interest (Gastric Pain Symptoms domain, Stomach Heaviness Symptoms domain, and Diarrhea Symptoms domain) scores of Izumo Scale from baseline. Histologic response defined as a \> 75% reduction of peak gastric and/or duodenal eos count from baseline. Izumo Scale tests 5 different GI symptom domains during past week and consists with 15 weekly questions (3 questions per 1 domain): Heartburn Symptoms domain(Ques1 through3), Gastric Pain Symptoms domain(Questions4 through6), Stomach Heaviness Symptoms domain(Ques7 through9), Constipation Symptoms domain (Question 10 through12), Diarrhea Symptoms domain (Ques13 through15). Each question is scored on a 6-point Likert scale of "0 = No trouble at all" to "5 = Can't stand it," and score for each question within a domain added to determine domain specific scores scaled from 0 to 15, with higher values indicating greater symptom severity.
Induction + Maintenance: Change From Baseline in Mean Number of Peak Eosinophils (Eos) Count Per High-power Field (Hpf) in Gastrointestinal (GI) Biopsies at Week 48	Baseline and Week 48	Blood samples were collected to assess eosinophils count. Baseline data are defined as last measurement collected on or prior the date of first dose for Induction Phase. Participants that discontinued Induction period without entering maintenance period are included in the CC-93538 360 mg QW arm
Induction Phase: Percent Changes in Mean Number of Peak Eos Per Hpf in GI Biopsies From Baseline	Baseline and Week 16	Blood samples were collected to assess eosinophils count. Baseline data are defined as last measurement collected on or prior the date of first dose for Induction Phase.
Induction + Maintenance: Percent Changes in Mean Number of Peak Eos Per Hpf in GI Biopsies From Baseline	Baseline and Week 48	Blood samples were collected to assess eosinophils count. Baseline data are defined as last measurement collected on or prior the date of first dose for Induction Phase. Participants that discontinued Induction period without entering maintenance period are included in the CC-93538 360 mg QW arm.
Induction Phase: Percentage of Participants With Eosinophil Histologic Response (> 75% Reduction)	Week 16	Histologic response defined as a \> 75% reduction of peak gastric and/or duodenal eos count from baseline.
Induction + Maintenance: Percentage of Participants With Eosinophil Histologic Response (> 75% Reduction)	Week 48	Histologic response defined as a \> 75% reduction of peak gastric and/or duodenal eos count from baseline. Participants that discontinued Induction period without entering maintenance period are included in the CC-93538 360 mg QW arm.
Induction Phase: Percentage of Participants Who Achieve <4/15 in Each of Three Symptoms of Interest Scores Using the Izumo Scale	Week 16	The Izumo Scale questionnaire assesses the comprehensive 5 different GI symptom domains during the past week and consists with 15 weekly questions (3 questions per 1 domain): Heartburn Symptoms domain(Questions1 through3), Gastric Pain Symptoms domain(Questions4 through6), Stomach Heaviness Symptoms domain(Questions7 through9), Constipation Symptoms domain (Question 10 through12), Diarrhea Symptoms domain (Questions13 through15). Each question is scored on a 6-point Likert scale of "0 = No trouble at all" to "5 = Can't stand it," and the score for each question within a domain is added to determine domain specific scores scaled from 0 to 15, with higher values indicating greater symptom severity. Gastric Pain Symptoms domain, Stomach Heaviness Symptoms domain, and Diarrhea Symptoms domain are Symptoms of Interest.
Induction + Maintenance: Percentage of Participants Who Achieve <4/15 in Each of Three Symptoms of Interest Scores Using the Izumo Scale	Baseline and Week 48	The Izumo Scale questionnaire assesses the comprehensive 5 different GI symptom domains during the past week and consists with 15 weekly questions (3 questions per 1 domain): Heartburn Symptoms domain(Questions1 through3), Gastric Pain Symptoms domain(Questions4 through6), Stomach Heaviness Symptoms domain(Questions7 through9), Constipation Symptoms domain (Question 10 through12), Diarrhea Symptoms domain (Questions13 through15). Each question is scored on a scale of "0 = No trouble at all" to "5 = Can't stand it," and one symptom domain is scored from 0 to 15, with higher values indicating greater symptom severity. Gastric Pain Symptoms domain, Stomach Heaviness Symptoms domain, and Diarrhea Symptoms domain are Symptoms of Interest. Participants that discontinued Induction period without entering maintenance period are included in the CC-93538 360 mg QW arm. Only participants from ages 12 -19 years old at specified timepoint are included in the analysis.
Induction Phase: Changes in Total Score of Eosinophilic Gastrointestinal Disorder (EGID) Severity Score From Baseline to Weeks 16 in Adolescent (12 to 19 Years)	Baseline and Week 16	The EGID Severity Score for participants from 12 to 19 years old assesses 6 different symptoms (vomiting, dysphagia, anorexia, abdominal pain, diarrhea, bloody stool), 2 clinical laboratory tests (albumin, eos ratio of peripheral blood cells) and general condition, including height and weight. The score ranges from 0 to 100 and the higher the score, the greater the severity. A score of ≥ 40 is considered as severe, a score of 15 to 39 as moderate and ≤ 14 score as mild.
Induction Phase: Changes in Total Score of EGID Severity Score From Baseline to Weeks 16 in Adults (>= 20 Years)	Baseline and Week 16	The EGID Severity Scores are assessed by the investigator. The EGID Severity Score for participants ≥ 20 years old assess the intensity and the frequency of 6 different symptoms (vomiting, dysphagia, anorexia, abdominal pain, diarrhea, bloody stool), 2 clinical laboratory tests (albumin, eos ratio of peripheral blood cells) and 2 medical history items (history of surgery and use of systemic corticosteroid or immunosuppressives). The score ranges from 0 to 82 and the higher the score, the greater the severity. A score of ≥ 40 is considered as severe, a score of 15 to 39 as moderate and a score of ≤ 14 score as mild.
Induction+ Maintenance: Changes in Total Score of EGID Severity Score From Baseline to Weeks 48 in Adolescent (12 to 19 Years)	Baseline and Week 48	The EGID Severity Score for participants from 12 to 19 years old assesses 6 different symptoms (vomiting, dysphagia, anorexia, abdominal pain, diarrhea, bloody stool), 2 clinical laboratory tests (albumin, eos ratio of peripheral blood cells) and general condition, including height and weight. The score ranges from 0 to 100 and the higher the score, the greater the severity. A score of ≥ 40 is considered as severe, a score of 15 to 39 as moderate and ≤ 14 score as mild. Participants that discontinued Induction period without entering maintenance period are included in the CC-93538 360 mg QW arm.
Induction + Maintenance: Changes in Total Score of EGID Severity Score From Baseline to Weeks 48 in Adults (>= 20 Years)	Baseline and Week 48	The EGID Severity Scores are assessed by the investigator. The EGID Severity Score for participants ≥ 20 years old assess the intensity and the frequency of 6 different symptoms (vomiting, dysphagia, anorexia, abdominal pain, diarrhea, bloody stool), 2 clinical laboratory tests (albumin, eos ratio of peripheral blood cells) and 2 medical history items (history of surgery and use of systemic corticosteroid or immunosuppressives). The score ranges from 0 to 82 and the higher the score, the greater the severity. A score of ≥ 40 is considered as severe, a score of 15 to 39 as moderate and a score of ≤ 14 score as mild. Participants that discontinued Induction period without entering maintenance period are included in the CC-93538 360 mg QW arm.
Induction Phase: Time to First Event of Eosinophilic Gastroenteritis (EGE) Flare and First Use of Rescue Therapy	Through Week 16	Any worsening of EGE symptoms during study participation will be documented as an EGE flare. Worsening of EGE symptoms is defined as continuous worsening of symptoms for 2 consecutive visits (4 weeks apart) compared to baseline, measured by the weekly Izumo Scale score (≥ 4 weeks of no change from baseline or ≥ 4 weeks of worsening from baseline).
Induction + Maintenance: Time to First Event of Eosinophilic Gastroenteritis (EGE) Flare and First Use of Rescue Therapy	Through Week 48	Any worsening of EGE symptoms during study participation will be documented as an EGE flare. Worsening of EGE symptoms is defined as continuous worsening of symptoms for 2 consecutive visits (4 weeks apart) compared to baseline, measured by the weekly Izumo Scale score (≥ 4 weeks of no change from baseline or ≥ 4 weeks of worsening from baseline). Participants that discontinued Induction period without entering maintenance period are included in the CC-93538 360 mg QW arm.
Maintenance Phase: Time to Reduce to Zero Concomitant Corticosteroid Use	From Week 16 through Week 48	Participants who use concomitant corticosteroid at baseline and entered Maintenance Phase
Percentage of Participants for Whom the Dose of Concomitant Steroids is Reduced to Zero	Week 24, 32, 40 and 48	Participants who use concomitant corticosteroid at baseline and entered Maintenance period were included in the analysis.
Induction and Maintenance: Number of Participants With Treatment-Emergent Adverse Events	From Day 1 untill Week 48	A treatment emergent adverse event (TEAE) is any AE that emerges during treatment or Safety Follow-up Period having been absent pre-treatment or worsens in severity relative to the pretreatment state. Participants that discontinued Induction period without entering maintenance period are included in the CC-93538 360 mg QW arm.
Induction and Maintenance: Number of Participants With Remarkable Differences of Clinically Relevant Mean Changes From Baseline in Vital Signs Measurements	From Day 1 untill Week 48	Participants that discontinued Induction period without entering maintenance period are included in the CC-93538 360 mg QW arm.
Induction and Maintenance: Number of Participants With Remarkable Differences of Clinically Relevant Mean Changes From Baseline in Physical Examinations Parameters	From Day 1 untill Week 48	Participants that discontinued Induction period without entering maintenance period are included in the CC-93538 360 mg QW arm.
Induction and Maintenance: Number of Participants With Mean Changes Over Time That Were of Clinically Concern in Hematology Parameters, Serum Chemistry Parameters, and Urinalysis Parameters	From Day 1 untill Week 48	Participants that discontinued Induction period without entering maintenance period are included in the CC-93538 360 mg QW arm.
Induction and Maintenance: Number of Participants With Anti-Drug-Antibody	From Day 1 till Week 48	Blood samples were collected to assess Anti-Drug-Antibody. Participants that discontinued Induction period without entering maintenance period are included in the CC-93538 360 mg QW arm.
Induction Phase: CC-93538 Trough Concentration at Week 16	Week 16	Blood samples were collected to assess CC-93538 trough concentrations.
Maintenance Phase: CC-93538 Trough Concentration at Week 48	Week 48	Blood samples were collected to assess CC-93538 trough concentrations. Participants that discontinued Induction period without entering maintenance period are included in the CC-93538 360 mg QW arm.

Trial Locations

Locations (25): Local Institution - 024
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Gifu, Gifu, Japan
Local Institution - 022
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Himeji-shi, Hyōgo, Japan
Local Institution - 009
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Nishinomiya, Hyōgo, Japan
Local Institution - 0025
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Tsu, Mie-ken, Japan
Local Institution - 025
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Tsu, Mie-ken, Japan
Local Institution - 023
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Sendai, Miyagi, Japan
Local Institution - 007
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Bunkyo-ku, Tokyo, Japan
Local Institution - 001
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Setagaya-ku, Tokyo, Japan
Local Institution - 010
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Akita, Japan
Local Institution - 017
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Hirosaki, Japan
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Local Institution - 024
🇯🇵Gifu, Gifu, Japan