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

Celgene

Status and phase: Active, not recruiting; Phase 3

Conditions: Eosinophilic Esophagitis

Treatments: Drug: CC-93538; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04753697

2020-004336-16 (EudraCT Number)

CC-93538-EE-001

U1111-1263-4351 (Registry Identifier)

Details and patient eligibility

About

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

Enrollment: 430 patients

Sex: All

Ages: 12 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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430 participants in 3 patient groups, including a placebo group

Administration of CC-93538

Experimental group

Description:

CC-93538 360 mg Subcutaneously (SC) once weekly for 24 weeks followed by CC-93538 360 mg SC once weekly for 24 weeks

Treatment:

Drug: CC-93538

Administration of CC-93538 and Placebo

Experimental group

Description:

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.

Treatment:

Other: Placebo

Drug: CC-93538

Administration of Placebo

Placebo Comparator group

Description:

Matching placebo SC once weekly for 24 weeks followed by matching placebo SC once weekly for 24 weeks

Treatment:

Other: Placebo