A study to evaluate the efficacy and safety of CC-93538 in adult and adolescent patients who have eosinophilic esophagitis

• Register: EUCTR
• Last refreshed on: 3 February 2025
• Main ID: EUCTR2020-004336-16-AT
• Date of registration: 22/03/2021
• Prospective Registration: Yes
• Primary sponsor: Celgene International II Sàrl
• Public title: A study to evaluate the efficacy and safety of CC-93538 in adult and adolescent patients who have eosinophilic esophagitis
• Scientific title: A Phase 3, Multi-Center, Multi-National, 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
• Date of first enrolment: 01/08/2021
• Target sample size: 399
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-004336-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Canada, Czechia, Germany, Israel, Italy, Japan, New Zealand, Poland, Portugal, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: GSM-CT
• Affiliation: Bristol-Myers Squibb International Corporation

• Name: GSM-CT
• Affiliation: Bristol-Myers Squibb International Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
•Male or female patients aged = 12 and =75 years, with a body weight of > 40 kg.
•Histologic evidence of EoE, defined as a peak count of = 15 eos/HPF at 2 levels of the esophagus.
•Subject-reported history of 4 or more Dysphagia Days within 2 consecutive weeks prior to end of screening.
•Lack of complete response to an adequate trial of PPI (8 weeks). Subjects on a PPI 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.
•Subjects 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.
•Subjects must agree to maintain a stable diet (including any food elimination for the treatment of food allergy or EoE) and not introduce any changes in their diet from the first Screening Visit to the end of the study.
•FCBP 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 30
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 366
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion criteria:
•Clinical or endoscopic evidence of other diseases that may affect the histologic, endoscopic, and clinical symptom evaluation for this study.
•Other GI disorders such as active Helicobacter pylori infection, esophageal varices, gastritis, colitis, celiac disease, Mendelian disorder associated with EoE, liver function impairment; or a known HFI.
•Evidence of a severe endoscopic structural abnormality in the esophagus.
•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.
•Evidence of immunosuppression, or of having received systemic immunosuppressive or immunomodulating drugs within 5 drug half-lives prior to the first Screening Visit.
•Treatment with a high potency topical corticosteroid for dermatologic use, or a systemic corticosteroid within 8 weeks of the first Screening Visit.
•Treatment with a swallowed topical corticosteroid, leukotriene receptor antagonist, or mast cell stabilizer for EoE, within 4 weeks of the first Screening Visit.
•Treatment with oral or sublingual immunotherapy within 6 months of the first Screening Visit (any use will be prohibited during the study). SC immunotherapy may be allowed if on stable doses for at least 3 months prior to the first Screening Visit and during the study.
•Actively successful dietary modification adherence (e.g. food elimination diet), resulting in a complete response to EoE.
•Prior treatment with CC-93538 during a Phase 1 or 2 clinical study.
•Receipt of a live attenuated vaccine within 4 weeks of the first Screening Visit.
•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, cardiovascular condition, neurologic disorder, or psychiatric illness that compromises the subject's ability to accurately document symptoms of EoE).
•Active or ongoing infections including parasitic/helminthic, hepatitis, TB, or AIDS.
•Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 4 weeks of the first Screening Visit.
•Females who are pregnant or lactating.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

EOSINOPHILIC ESOPHAGITIS
MedDRA version: 20.1 Level: LLT Classification code 10064220 Term: Eosinophilic esophagitis System Organ Class: 100000004856

Therapeutic area: Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]

Intervention(s)

Product Name: Cendakimab
Product Code: CC-93538
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Cendakimab
Current Sponsor code: CC-93538
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: -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 Objective: -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
-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

Timepoint(s) of evaluation of this end point: Week 24

Primary end point(s): •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

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1/ week 24
2/ week 24
3/ week 24
4/ week 24
5/ week 24
6/ week 48
7/ week 48
8/ Determined through the whole study
9/ Determined through the whole study
10/ Week 24
11/ Week 24

Secondary end point(s): 1/The proportion of subjects with eosinophilic histologic response defined as a peak esophageal eosinophil count < 15/hpf at Week 24
2/The mean change in the endoscopic features of EoE as measured by the EoE Endoscopic Reference Score (EREFS) from baseline to Week 24
3/The mean change in the mean adjusted histology grade score as measured by the EoE histology scoring system (EoEHSS) from baseline to Week 24
4/The mean change in the mean adjusted histology stage score as measured by the EoE histology scoring system (EoEHSS) from baseline to Week 24
5/The mean change in the modified Daily Symptom Diary (mDSD) composite score from baseline to Week 24
6/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
7/The proportion of subjects with eosinophilic histologic response defined as a peak esophageal eosinophil count = 6/high-power field (hpf) at Week 48
8/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
9/Measurements of trough concentrations of CC-93538 in subjects with EoE
10/The proportion of subjects with a = 50% decrease in dysphagia days (DD) from baseline at Week 24
11/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

Secondary ID(s)

2020-004336-16-DE

NCT04753697

CC-93538-EE-001

Source(s) of Monetary Support

Celgene Corporation

Ethics review

Status: Approved
Approval date: 26/07/2021
Contact:

Results

• Results available: Yes
• Date Posted: 26/01/2025
• Date Completed: 29/08/2024
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-004336-16/results