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 Subjects with Eosinophilic Esophagitis
- Conditions
- Eosinophilic esophagitis
- Registration Number
- JPRN-jRCT2051200140
- Lead Sponsor
- Inoue Tomoyoshi
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- All
- Target Recruitment
- 33
1. Subject must be >= 12 years and <= 75 years of age and have a body weight of >= 40 kg(88.2 lb) at the time of signing the informed consent form (ICF)/assent form.
2. Subject has histologic evidence of EoE, defined as a peak count of >= 15 eosinophils per high-power field (hpf) at any 2 levels of the esophagus (proximal, mid, and/or distal) when off anti-inflammatory therapy (eg, corticosteroids) for EoE. The histologic criterion for diagnosis of EoE must be confirmed by a centrally read histological assessment of an EGD specimen during the Screening Period prior to randomization.
3. Subject has symptoms of dysphagia of at least 4 DD, as assessed with the mDSD instrument, over the last 2 consecutive weeks (14 days) prior to Day 1 when off antiinflammatory therapy (eg, corticosteroids) for EoE. Subjects are required to have at least 11 days of diary data out of the final 14-day period of screening mDSD collection in order to be enrolled in the study. During these 11 days, responses to questions 2 through 5 of the mDSD instrument must be complete.
4. Subject must have previously received an adequate trial of proton-pump inhibitor (PPI) medication (8 weeks per guidance) that did not provide complete response to EoE, or the subject remains symptomatic with continued use. Prospective subjects who discontinued use of a PPI must not have received a PPI for at least 4 weeks before their first Screening Visit and must agree not to restart a PPI during the study. If a prospective subject is receiving a PPI medication at screening, he or she must have been receiving a stable dose for at least 4 weeks prior to the first Screening Visit and agree to continue the same dose throughout the study.
5. Subject must either (1) be naive or have had an adequate response to corticosteroid therapy (ie, classified as Steroid Responders/Naive) or (2) have had an inadequate response to corticosteroid therapy and is not considered to be a candidate for continued corticosteroid therapy, or is intolerant to corticosteroid therapy. For subjects who have previously received systemic or swallowed topical corticosteroids for EoE, designation of the status of Steroid Inadequate Responders/Intolerant will include either of the following definitions. Note that if any of the below criteria are met, a subject will be deemed Steroid Inadequate Responders/Intolerant (approximately 70% of the study population) and cannot be classified as Steroid Responders/Naive (approximately 30% of the study population).
a. Inadequate response to corticosteroid therapy (failed to respond or lost response) and not considered a candidate for continued corticosteroid therapy: subjects who have had a trial of at least 6 weeks of swallowed topical corticosteroid treatment or 4 weeks of systemic corticosteroids at doses in accordance to published guidelines for the management of EoE, or a trial for the treatment duration specified in the prescribing information for approved products and judged by the treating physician as not achieving clinical improvement or having clinical improvement initially but lost response while on therapy.
b. Intolerant to corticosteroid therapy: subjects who initiated systemic or swallowed topical corticosteroid treatment but were unable to achieve treatment durations or dose levels due to intolerance because of side effects, including intolerance from use of corticosteroids for conditions other than EoE, or subjects with underlying conditions in which corticosteroid us
1. Subject has clinical or endoscopic evidence of the presence of any other disease that may interfere with or affect the histologic, endoscopic, and clinical symptom endpoints for this study (eg, erosive esophagitis Los Angeles [LA] classification Grade B or above, Barrett's esophagus, esophageal lichen planus, upper gastrointestinal bleed, achalasia, inflammatory bowel disease, diagnosed eosinophilic gastroenteritis [clinical symptoms and/or EGD findings and confirmatory eosinophilia in gastric and/or duodenal mucosa], or significant hiatal hernia [> 3 cm], etc.).
2. Subject demonstrates presence of esophageal varices.
3. Subject has a known active Helicobacter pylori infection and/or is currently being treated for this condition.
4. Subject has evidence of a severe endoscopic structural abnormality in the esophagus (eg, high-grade stenosis where an 8- to 10-mm endoscope could not pass through the stricture without dilation at the time of the screening EGD).
5. Subject had esophageal dilation for symptom relief during the Screening Period or within 8 weeks prior to the first Screening Visit, or esophageal dilation is anticipated to be performed within 48 weeks of dosing during the study.
6. Subject demonstrates evidence of immunosuppression or is receiving systemic immunosuppressive or immunomodulating drugs (eg, anti-IL-13 antibodies [except IP in this study], IL-4 receptor alpha antagonist antibodies [eg, dupilumab], anti-IL-5 antibodies, anti-IL-17 antibodies, anti-immunoglobulin E [IgE] antibodies, alpha 4 beta 7 integrin inhibitor antibodies, or any other monoclonal antibody, methotrexate, cyclosporine, azathioprine, mercaptopurine, interferon alpha [IFN alpha], tumor necrosis factor alpha [TNF alpha] inhibitors, etc.) within 5 drug half-lives prior to the first Screening Visit. Any use of these medications will be prohibited during the study.
7. Subject is currently receiving systemic or swallowed topical corticosteroid medication. Prospective subjects with EoE previously treated with a corticosteroid must not have received a systemic corticosteroid within 8 weeks or swallowed topical corticosteroid within 4 weeks of the first Screening Visit.
8. Subject is currently receiving a high potency topical corticosteroid (eg, augmented betamethasone dipropionate, clobetasol propionate, etc.) for dermatologic use. Prospective subjects must not have received a high potency topical corticosteroid for dermatologic use within 8 weeks of the first Screening Visit. Any use will be prohibited during the study.
9. Subject is currently receiving a leukotriene receptor antagonist (eg, montelukast) or mast cell stabilizer (eg, cromolyn sodium) for the indication of EoE. Subjects must not have received a leukotriene receptor antagonist or mast cell stabilizer for EoE within 4 weeks of the first Screening Visit. Any use for the treatment of EoE during the study will be prohibited.
10. Subject is currently successfully treated for EoE with dietary modifications (eg, food elimination diet) and is able to fully adhere to the diet resulting in a complete response to EoE (ie, the subject does not meet the symptoms of dysphagia requirement of at least 4 DD and histologic criterion for diagnosis of EoE per Inclusion Criteria 2 and 3).
11. Subject has received oral or sublingual immunotherapy within 6 months of the first Screening Visit; any use will be prohibited during the study. Subjects receiving SC immunotherapy may participate but must be on stable do
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Induction Phase Endpoints at Week 24:<br>- 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<br>- Eosinophil Histologic Response (<=6/hpf):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 Measures
Name Time Method Induction Phase Key Secondary Endpoints at Week 24:<br>- Eosinophil Histologic Response (<15/hpf):The proportion of subjects with eosinophilic histologic response defined as a peak esophageal eosinophil count < 15/hpf at Week 24<br>- EREFS:The mean change in the endoscopic features of EoE as measured by the EoE Endoscopic Reference Score (EREFS) from baseline to Week 24<br>- 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<br>- 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<br>- mDSD Composite Score:The mean change in the modified Daily Symptom Diary (mDSD) composite score from baseline to Week 24