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

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ClinicalTrials.gov Identifier: NCT04753697
Recruitment Status : Recruiting
First Posted : February 15, 2021
Last Update Posted : April 23, 2021
Sponsor:
Information provided by (Responsible Party):
Celgene

Brief Summary:

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

Condition or disease Intervention/treatment Phase
Eosinophilic Esophagitis Drug: CC-93538 Other: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 468 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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.
Actual Study Start Date : February 22, 2021
Estimated Primary Completion Date : November 23, 2023
Estimated Study Completion Date : May 23, 2024

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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




Primary Outcome Measures :
  1. Change in DD Clinical Response [ Time Frame: At week 24 ]
    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

  2. Eosinophil Histologic Response (≤ 6/hpf) [ Time Frame: At week 24 ]
    The proportion of participants with eosinophilic histologic response defined as a peak esophageal eosinophil count ≤ 6/high-power field (hpf) at Week 24


Secondary Outcome Measures :
  1. Eosinophil Histologic Response (< 15/hpf) [ Time Frame: At week 24 ]
    The proportion of participants with eosinophilic histologic response defined as a peak esophageal eosinophil count < 15/hpf at Week 24

  2. EoE Endoscopic Reference Score (EREFS) [ Time Frame: At week 24 ]
    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

  3. EoEHSS Grade Score [ Time Frame: At week 24 ]
    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. EoEHSS Stage Score [ Time Frame: At week 24 ]
    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. mDSD Composite Score [ Time Frame: At week 24 ]
    The mean change in the modified Daily Symptom Diary (mDSD) composite score from baseline to Week 24

  6. DD Clinical Responder Definition [ Time Frame: At week 24 ]
    The proportion of participants with a ≥ 50% decrease in dysphagia days (DD) from baseline at Week 24

  7. Kinetics and Onset of Clinical Response_DD [ Time Frame: Through week 24 ]
    The mean change in dysphagia days (DD) over time from baseline through Week 24

  8. Kinetics and Onset of Clinical Response_mDSD [ Time Frame: Through week 24 ]
    The mean change in the modified Daily Symptom Diary (mDSD) composite score over time from baseline through Week 24

  9. Time to Event _EoE Flare [ Time Frame: Through week 24 ]
    The time to event of Eosinophilic Esophagitis (EoE) flare during the Induction Phase

  10. Time to Event_Rescue Therapy [ Time Frame: Through Week 24 ]
    The time to event of use of rescue therapy during the Induction Phase

  11. Proportion of Participants with Event-EoE Flare [ Time Frame: Through week 24 ]
    The proportion of participants with an EoE flare during the Induction Phase

  12. Proportion of Participants with Event_Rescue Therapy [ Time Frame: Through week 24 ]
    The proportion of participants with use of rescue therapy during the Induction Phase

  13. Incidence of Adverse Events (AEs) [ Time Frame: Through week 48 ]
    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

  14. Assessment of Immunogenicity through measurement of serum concentrations of anti-drug antibodies to CC-93538 [ Time Frame: Through week 48 ]
    Evaluated by the presence of anti-drug antibodies to CC-93538

  15. Pharmacokinetics- Ctrough [ Time Frame: Through week 24 ]
    Serum trough concentration Measurements of trough concentrations of CC-93538 in participants with EoE during the Induction Phase

  16. Change in DD Clinical Response [ Time Frame: At week 48 ]
    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

  17. Eosinophil Histologic Response (≤ 6/hpf) [ Time Frame: At week 48 ]
    The proportion of participants with eosinophilic histologic response defined as a peak esophageal eosinophil count ≤ 6/high-power field (hpf) at Week 48

  18. Eosinophil Histologic Response (< 15/hpf) [ Time Frame: At week 48 ]
    The proportion of participants with eosinophilic histologic response defined as a peak esophageal eosinophil count < 15/hpf at Week 48

  19. Mean change in EREFS [ Time Frame: At week 48 ]
    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

  20. EoEHSS Grade Score [ Time Frame: At week 48 ]
    The mean change in the mean adjusted histology grade score as measured by the EoE histology scoring system (EoEHSS) from baseline to Week 48

  21. EoEHSS Stage Score [ Time Frame: At week 48 ]
    The mean change in the mean adjusted histology stage score as measured by the EoE histology scoring system (EoEHSS) from baseline to Week 48

  22. mDSD Composite Score [ Time Frame: At week 48 ]
    The mean change in the modified Daily Symptom Diary (mDSD) composite score from baseline to Week 48

  23. Time to event_EoE Flare (Induction and Maintenance Phase) [ Time Frame: Through week 48 ]
    The time to event of EoE flare during the study

  24. Time to event_rescue therapy (Induction and Maintenance Phase) [ Time Frame: Through week 48 ]
    The time to event of use of rescue therapy during the study

  25. Proportion of Participants with Event_EoE Flare (Induction and Maintenance Phase) [ Time Frame: Through week 48 ]
    The proportion of participants with an EoE flare during the study

  26. Proportion of participants with event rescue therapy (Induction and Maintenance Phases) [ Time Frame: Through week 48 ]
    The proportion of participants with use of rescue therapy during the study

  27. Pharmacokinetics-Ctrough [ Time Frame: Through week 48 ]
    Measurements of trough concentrations of CC-93538 in participants with EoE during the Maintenance Phase



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04753697


Contacts
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Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@bms.com

Locations
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Sponsors and Collaborators
Celgene
Investigators
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Study Director: Cristian Rodriguez, MD Bristol-Myers Squibb
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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT04753697    
Other Study ID Numbers: CC-93538-EE-001
U1111-1263-4351 ( Registry Identifier: WHO )
2020-004336-16 ( EudraCT Number )
First Posted: February 15, 2021    Key Record Dates
Last Update Posted: April 23, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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/

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: See Plan Description
Access Criteria: See Plan Description
URL: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Celgene:
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
Additional relevant MeSH terms:
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Esophagitis
Eosinophilic Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases