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 |
A chronic allergic/immune condition characterized by inflammation of the esophagus |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10017947 |
E.1.2 | Term | Gastrointestinal disorders |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064212 |
E.1.2 | Term | Eosinophilic oesophagitis |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The Primary objective is to demonstrate the efficacy of dupilumab treatment compared with placebo in pediatric patients with active eosinophilic esophagitis (EoE) based on histologic improvement meeting validated histologic criteria. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are: •To demonstrate efficacy of dupilumab compared to placebo in pediatric patients with active EoE after 16 weeks of treatment as assessed by endoscopic visual measurements of disease activity using the Eosinophilic Esophagitis-Endoscopic Reference Score (EoE-EREFS) and histologic abnormalities as measured by the EoE Histology Scoring System (EoE-HSS) •To evaluate safety, tolerability, & immunogenicity of dupilumab treatment for up to 16 weeks in pediatric patients with active EoE •To evaluate effects of dupilumab on transcriptomic signatures associated with EoE and type 2 inflammation •To study effects of dupilumab on the type 2 inflammation gene expression signature •To evaluate concentration-time profile of functional dupilumab in serum •To assess efficacy of long-term (52 weeks) dupilumab treatment •To assess safety, tolerability, and immunogenicity of long-term dupilumab treatment •To evaluate impact of dupilumab treatment on EoE signs & symptoms |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Key Inclusion Criteria: •A documented diagnosis of eosinophilic esophagitis (EoE) •Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration (peak eosinophil count ≥15 eos/hpf; [400 x]) |
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E.4 | Principal exclusion criteria |
Key Exclusion Criteria: •Body weight <5 kg or ≥60 kg at screening •Other causes of esophageal eosinophilia •Active Helicobacter pylori •History of Crohn's disease, ulcerative colitis, celiac disease, or prior esophageal surgery •Any esophageal stricture unable to be passed with a standard, diagnostic, upper endoscope or any critical esophageal stricture that requires dilation at screening •Treatment with swallowed topical corticosteroids within 8 weeks prior to baseline standard of care endoscopy •History of bleeding disorders or esophageal varices that, in the opinion of the investigator, would put the patient at undue risk for significant complications from an endoscopy procedure •Active parasitic infection or suspected parasitic infection •Known or suspected immunodeficiency disorder
NOTE: Other protocol defined inclusion/exclusion criteria apply
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients achieving peak esophageal intraepithelial eosinophil count ≤6 eos/hpf (400×) |
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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.Proportion of patients achieving peak esophageal intraepithelial eosinophil count ≤6 eos/hpf (400×) [ Time Frame: At week 52 ] 2.Proportion of patients achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf [ Time Frame: At week 16 ] 3.Proportion of patients achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf [ Time Frame: At week 52 ] 4.Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) [ Time Frame: At week 16 ] 5.Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) [ Time Frame: At week 52 ] 6.Absolute change in mean eosinophilic esophagitis (EoE) Histology Scoring System (EoE-HSS) [ Time Frame: At week 16 ] 7.Absolute change in mean eosinophilic esophagitis (EoE) Histology Scoring System (EoE-HSS) [ Time Frame: At week 52 ] 8.Absolute change in Eosinophilic Esophagitis-Endoscopic Reference (EoE EREFS) [ Time Frame: At week 16 ] 9.Absolute change in Eosinophilic Esophagitis-Endoscopic Reference (EoE EREFS) [ Time Frame: At week 52 ] 10.Change in the type 2 inflammation transcriptional signature [ Time Frame: At week 16 ] 11.Change in the type 2 inflammation transcriptional signature [ Time Frame: At week 52 ] 12.Change in the proportion of days with 1 or more EoE signs as measured by the Pediatric EoE Sign/Symptom Questionnaire- caregiver version (PESQ-C) [ Time Frame: At week 16 ] For patients aged ≥1 to <12 years 13.Change in the proportion of days with 1 or more EoE signs as measured by the PESQ-C [ Time Frame: At week 52 ] For patients aged ≥1 to <12 years 14.Change in the proportion of total segments within a day with 1 or more EoE signs as measured by PESQ-C [ Time Frame: At week 16 ] For patients aged ≥1 to <12 years 15.Change in the proportion of total segments within a day with 1 or more EoE signs as measured by PESQ-C [ Time Frame: At week 52 ] For patients aged ≥1 to <12 years 16.Change in the proportion of days with 1 or more EoE symptoms as measured by the Pediatric EoE Sign/Symptom Questionnaire-patient version (PESQ-P) [ Time Frame: At week 16 ] For patients aged ≥8 to <12 years 17.Change in the proportion of days with 1 or more EoE symptoms as measured by PESQ-P [ Time Frame: At week 52 ] For patients aged ≥8 to <12 years 18.Change in the proportion of total segments within a day with 1 or more EoE symptoms as measured by PESQ-P [ Time Frame: At week 16 ] For patients aged ≥8 to <12 years 19.Change in the proportion of total segments within a day with 1 or more EoE symptoms as measured by PESQ-P [ Time Frame: At week 52 ] For patients aged ≥8 to <12 years 20.Change in total score as measured by the PEESSv2.0-caregiver version questionnaire [ Time Frame: At week 16 ] For patients aged ≥1 to <12 years 21.Normalized Enrichment Scores (NES) for the relative change in the EoE diagnostic panel (EDP) transcriptome signature [ Time Frame: At week 16 ] 22.NES for the relative change in the EDP transcriptome signature [ Time Frame: At week 52 ] 23.NES for the relative change in the type 2 inflammation transcriptome signature [ Time Frame: At week 16 ] 24.NES for the relative change in the type 2 inflammation transcriptome signature [ Time Frame: At week 52 ] 25.Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: At week 16 ] 26.Incidence of TEAEs [ Time Frame: At week 52 ] 27.Incidence of treatment-emergent serious adverse events (SAEs) [ Time Frame: At week 16 ] 28.Incidence of treatment-emergent SAEs [ Time Frame: At week 52 ] 29.Incidence of treatment-emergent adverse events of special interest (AESIs) [ Time Frame: At week 16 ] 30.Incidence of treatment-emergent AESIs [ Time Frame: At week 52 ] 31.Incidence of TEAEs leading to permanent discontinuation of study treatment [ Time Frame: At week 16 ] 32.Incidence of TEAEs leading to permanent discontinuation of study treatment [ Time Frame: At week 52 ] 33.Incidence of treatment-emergent Anti-drug antibody (ADA) responses and titer [ Time Frame: At week 16 ] 34.Incidence of treatment-emergent ADA responses and titer [ Time Frame: At week 52 ] 35.Concentration of functional dupilumab in serum [ Time Frame: Up to week 52 ] |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At week 52; At week 16; Up to week 52 |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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 | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 3 |