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

Study Overview
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Brief Summary
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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

Official Title
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A Multi-Center, Multi-National, Randomized, Double-Blind, Placebo-Controlled Induction and Long-term Controlled Study to Evaluate the Efficacy and Safety of CC-93538 in Adult and Adolescent Subjects With Active Eosinophilic Esophagitis.

Conditions
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Eosinophilic Esophagitis

Intervention / Treatment
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* Drug: CC-93538
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must satisfy the following criteria to be enrolled in the study: Male or female patients aged ≥ 12 and ≤ 75 years, with a body weight of > 40 kg. 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: Clinical or endoscopic evidence of other diseases that may affect the histologic, endoscopic, and clinical symptom evaluation for this study. 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. 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). Subcutaneous 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, or cardiovascular condition, or neurologic disorder or psychiatric illness that compromises the Participant's ability to accurately document symptoms of eosinophilic esophagitis). Active or ongoing infections including parasitic/helminthic, hepatitis, tuberculosis, or human immunodeficiency virus. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 4 weeks of the first Screening Visit. Females who are pregnant or lactating.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Administration of CC-93538<br>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<br>* Subcutaneous<br>* Other names: RPC4046;|
| Experimental: Administration of CC-93538 and Placebo<br>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<br>* Subcutaneous<br>* Other names: RPC4046;Other: Placebo<br>* Subcutaneous<br>|
| Placebo Comparator: Administration of Placebo<br>Matching placebo SC once weekly for 24 weeks followed by matching placebo SC once weekly for 24 weeks | Other: Placebo<br>* Subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | At week 24 | 
| Eosinophil Histologic Response (≤ 6/hpf) | The proportion of participants with eosinophilic histologic response defined as a peak esophageal eosinophil count ≤ 6/high-power field (hpf) at Week 24 | At week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eosinophil Histologic Response (< 15/hpf) | The proportion of participants with eosinophilic histologic response defined as a peak esophageal eosinophil count < 15/hpf at Week 24 | At week 24 | 
| EoE Endoscopic Reference Score (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 | At 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 | At 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 | At week 24 | 
| mDSD Composite Score | The mean change in the modified Daily Symptom Diary (mDSD) composite score from baseline to Week 24 | At week 24 | 
| DD Clinical Responder Definition | The proportion of participants with a ≥ 50% decrease in dysphagia days (DD) from baseline at Week 24 | At week 24 | 
| Kinetics and Onset of Clinical Response_DD | The mean change in dysphagia days (DD) over time from baseline through Week 24 | Through week 24 | 
| Kinetics and Onset of Clinical Response_mDSD | 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 _EoE Flare | The time to event of Eosinophilic Esophagitis (EoE) flare during the Induction Phase | Through week 24 | 
| Time to Event_Rescue Therapy | The time to event of use of rescue therapy during the Induction Phase | Through Week 24 | 
| Proportion of Participants with Event-EoE Flare | The proportion of participants with an EoE flare during the Induction Phase | Through week 24 | 
| Proportion of Participants with Event_Rescue Therapy | The proportion of participants with use of rescue therapy during the Induction Phase | Through week 24 | 
| Incidence of Adverse Events (AEs) | An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant 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 participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE except for symptoms associated with an EoE flare requiring an EoE Flare Assessment | Through week 48 | 
| Assessment of Immunogenicity through measurement of serum concentrations of anti-drug antibodies to CC-93538 | Evaluated by the presence of anti-drug antibodies to CC-93538 | Through week 48 | 
| Pharmacokinetics- Ctrough | Serum trough concentration Measurements of trough concentrations of CC-93538 in participants with EoE during the Induction Phase | Through week 24 | 
| 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 | At week 48 | 
| Eosinophil Histologic Response (≤ 6/hpf) | The proportion of participants with eosinophilic histologic response defined as a peak esophageal eosinophil count ≤ 6/high-power field (hpf) at Week 48 | At week 48 | 
| Eosinophil Histologic Response (< 15/hpf) | The proportion of participants with eosinophilic histologic response defined as a peak esophageal eosinophil count < 15/hpf at Week 48 | At week 48 | 
| Mean change in 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 | At 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 | At 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 | At week 48 | 
| mDSD Composite Score | The mean change in the modified Daily Symptom Diary (mDSD) composite score from baseline to Week 48 | At week 48 | 
| Time to event_EoE Flare (Induction and Maintenance Phase) | The time to event of EoE flare during the study | Through week 48 | 
| Time to event_rescue therapy (Induction and Maintenance Phase) | The time to event of use of rescue therapy during the study | Through week 48 | 
| Proportion of Participants with Event_EoE Flare (Induction and Maintenance Phase) | The proportion of participants with an EoE flare during the study | Through week 48 | 
| Proportion of participants with event rescue therapy (Induction and Maintenance Phases) | The proportion of participants with use of rescue therapy during the study | Through week 48 | 
| Pharmacokinetics-Ctrough | Measurements of trough concentrations of CC-93538 in participants with EoE during the Maintenance Phase | Through week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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