E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Eosinophilic Esophagitis (EoE) |
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E.1.1.1 | Medical condition in easily understood language |
Eosinophilic Esophagitis (EoE) Allergic Esophagitis |
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E.1.1.2 | Therapeutic area | Not possible to specify |
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 | 100000004856 |
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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 evaluate the effect of benralizumab Dose Regimen 1 on histologic signs and symptoms of EoE in patients with symptomatic and histologically active EoE. |
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E.2.2 | Secondary objectives of the trial |
DB treatment period: -To evaluate the effect of benralizumab Dose Regimen 1 on clinical features of EoE and disease activity. -To evaluate the effect of benralizumab Dose Regimen 1 on patient reported QOL measures. -To evaluate the effect of benralizumab Dose Regimen 1 on healthcare resource utilization due to EoE. -To evaluate the effect of benralizumab Dose Regimen 1 on patient reported measures of disease severity and health status. -To assess the PK and immunogenicity of benralizumab Dose Regimen 1 in patients with EoE. -To assess the safety and tolerability of benralizumab Dose Regimen 1 in patients 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 |
1. EndoFLIP (Endolumenal Functional Lumen Imaging Probe) Objective: To evaluate the effect of benralizumab Dose Regimen 1 on clinical features of EoE and disease activity. 2. Qualitative Interview Sub-study. Objective: To characterize the health-related quality of life impact of EoE and of study treatment. 3. Pediatric Eosinophilic Esophagitis Symptom Severity Module, Version 2, Children and Teens Report (PEESS) Objective: To assess EoE symptom severity and frequency in patients who are age 18 years or under at Visit 1 4. Early Time Point Sub-study (only adult patients) Objective: To evaluate the effect of benralizumab Dose Regimen 1 on early histologic signs, clinical features, symptoms and biomarkers of EoE. |
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E.3 | Principal inclusion criteria |
- Patients 12 to 65 years of age, inclusive, at the time of signing the informed consent or assent (if applicable) form. -Documented previous diagnosis of EoE by endoscopy (documented diagnosis defined as an esophageal count of ≥15 eos/hpf on at least 1 esophageal level) and confirmed diagnosis by a centrally-read esophageal biopsy for the purposes of this study (confirmed diagnosis defined as an esophageal count of ≥15 eos/hpf at 2 or more esophageal levels). Two to 4 biopsies should be obtained from both the proximal and distal esophagus. Biopsies can be taken from the mid-esophagus for additional evaluation. -Must be symptomatic at Visit 1 (screening) and Visit 2 (randomization): (a) A patient reported average of at least 2 days per week with an episode of dysphagia over the 4 weeks prior to Visit 1 AND (b) An average of at least 2 days per week with an episode of dysphagia (Daily DSQ ≥2) between Visit 1 and Visit 2, and at least 2 days per week with an episode of dysphagia (Daily DSQ ≥2) in each of the 2 weeks immediately prior to randomization -Must be adherent to daily diary assessments: (a) Must complete 70% of daily diaries between Visit 1 and Visit 2; AND (b) Must have completed at least 8 of 14 daily diaries in the 14 days prior to randomization. -May be on background medications for EoE and related treatments during the study as long as the background medications have been stable for at least 4 weeks (8 weeks for PPI) prior to screening. -Body weight of at least 35 kg. -Negative serum pregnancy test for female patients of childbearing potential at Visit1. -Women of childbearing potential must agree to use a highly effective form of birth control (confirmed by the Investigator) from randomization throughout the study duration and within 16 weeks after last dose if IP. |
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E.4 | Principal exclusion criteria |
-Other GI disorders such as active Helicobacter pylori infection, history of achalasia, esophageal varices, Crohn's disease, ulcerative colitis, inflammatory bowel disease, or celiac disease. -Esophageal stricture that prevents the easy passage of a standard endoscope or any critical esophageal stricture that requires dilation during the run-in period. -Esophageal dilation performed within 8 weeks prior to screening and prior esophageal surgery would impact the assessments for EoE. -Use of a feeding tube, or having a pattern of not eating solid food daily during the run-in period. -Hypereosinophilic syndrome, defined by multiple organ involvement and persistent blood eosinophil count >1500 eos/μL. -EGPA vasculitis. -Eosinophilic gastritis, gastroenteritis, enteritis, or colitis documented by biopsy. -Current malignancy, or history of malignancy with some specific exceptions. -History of anaphylaxis to any biologic therapy or vaccine. -Current active liver disease: a) Chronic stable hepatitis B and C (including positive testing for hepatitis B surface antigen [HBsAg] or hepatitis C antibody), or other stable chronic liver disease are acceptable if the patient otherwise meets eligibility criteria. b) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level≥3 times the upper limit of normal (ULN), confirmed by repeated testing during the run-in period. -Helminth parasitic infection diagnosed within 24 weeks prior to screening that has not been treated with or has failed to respond to standard of care therapy. -History of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test. -Concomitant use of immunosuppressive medication. -Initiation or change of a food-elimination diet regimen or reintroduction of a previously eliminated food group in the 6 weeks prior to the start of and during the run-in period. -Currently pregnant, breastfeeding, or lactating women. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Dual-primary Endpoints: -Proportion of patients with a histologic response at Week 24, defined as a peak esophageal intraepithelial eosinophil count ≤ 6 eos/hpf - Changes from baseline in DSQ score 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) |
Study Objectives for the DB treatment period: -Key secondary endpoint: Percent change from baseline in tissue eosinophils at Week 24 -Key secondary endpoint: Change from baseline in EoE-HSS grade score at Week 24 -Key secondary endpoint: Change from baseline in EoE-HSS stage score at Week 24 -Key secondary endpoint: Changes from baseline in centrally-read EoE EREFS at Week 24 -Key secondary endpoint Treatment responder rate at Week 24, defined as a composite of histological response (≤ 6 eos/hpf) and clinically meaningful improvement from baseline in DSQ (30% improvement) -Centrally-read biopsies for additional histopathology including tissue eosinophil counts at Week 24 -Dysphagia-free days as captured by the DSQ -Frequency of dysphagia episodes as captured by the EoE-3D -Changes from baseline in dysphagia associated pain, discomfort, and overall severity as captured by the EoE-3D at Week 24 -Changes from baseline in abdominal pain and nausea as captured by the daily diary at Week 24 -Changes from baseline in PEESS at Week 24 -Changes from baseline in EoE-QoL-A at Week 24 -SF-36 v2 Health Survey at Week 24 - Percent of patients with relevant concomitant procedures and healthcare resource utilization during the study through Week 24 -PGI-S at Week 24 - PGI-C at Week 24 -Serum benralizumab concentration -ADA and nAb -Safety and tolerability will be evaluated in terms of AEs, Vital signs, and Clinical laboratory values |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Varies depending on the endpoint/objective |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
Samples collected for the Genomics Initiative are considered primary use and will be whole exome or whole genome sequenced. Analysis will be performed for both known and novel health related genes and this broad genetic research will not restrict to disease or drug. Sequencing data generated is for research purposes only and cannot be used for clinical decision making and there will not be any clinical endpoints delivered to the study, as a result of testing performed. |
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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 | Yes |
E.8.1.7.1 | Other trial design description |
Following DB treatment ,patients continue with Open Label benralizumab Dosing Regimen1 to Week 52 |
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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 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
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 |
Canada |
Israel |
Japan |
United States |
France |
Poland |
Netherlands |
Spain |
Germany |
Italy |
Russian Federation |
United Kingdom |
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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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DB treatment followed by OL benralizumab dosing to Week 52. Option for at least 1 year OLE treatment |
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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 | 2 |
E.8.9.1 | In the Member State concerned days | 5 |
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 |