E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Eosinophilic esophagitis (EoE) is a chronic disease that affects food intake and quality of life. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Digestive System and Oral Physiological Phenomena [G10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064220 |
E.1.2 | Term | Eosinophilic esophagitis |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
-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 |
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E.2.2 | Secondary objectives of the trial |
-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 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: Endolumenal Functional Lumen Imaging Probe (EndoFLIP TM) Sub- study Objective: An optional sub-study will be performed at a subset of clinical sites utilizing an Endolumenal Functional Lumen Imaging Probe (EndoFLIP) to evaluate the effects of CC-93538 on esophageal distensibility. Version: Protocol version Final 30Sep2020 |
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E.3 | Principal 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | 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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 |
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
New Zealand |
Switzerland |
Australia |
Canada |
Israel |
Japan |
United Kingdom |
United States |
Austria |
Belgium |
Czechia |
Germany |
Italy |
Poland |
Portugal |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The End of Study is defined as either the date of the last visit of the last subject to complete the post-treatment follow-up, or the date of receipt of the last data point from the last subject that is required for primary, secondary, and/or exploratory analysis, as pre-specified in the protocol, whichever is the later date. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 17 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |