E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active eosinophilic esophagitis |
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E.1.1.1 | Medical condition in easily understood language |
Chronic allergic/immune-mediated inflammatory disease of the gullet in its active phase |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
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 assess the efficacy of budesonide effervescent tablets vs. placebo for the induction of clinico-pathological remission in adult patients with active eosinophilic esophagitis (EoE). |
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E.2.2 | Secondary objectives of the trial |
• To study safety and tolerability in the form of adverse events and laboratory parameters,
• To assess patients’ quality of life.
Exploratory:
• To study biomarkers in EoE.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed informed consent,
- Male or female patients, 18 to 75 years of age,
- Confirmed clinico-pathological diagnosis of EoE according to established diagnostic criteria ,
- Active symptomatic and histological EoE,
- A documented trial with proton pump inhibitors (PPIs) in order to rule out PPI-responsive esophageal eosinophilia,
- Negative pregnancy test in females of childbearing potential at baseline visit |
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E.4 | Principal exclusion criteria |
- Clinical signs (i.e., acid regurgitation and/or heart burn) and endoscopic signs (at least Los Angeles Classification of Esophagitis Grade A) of gastroesophageal reflux disease (GERD),
- History of abnormal results in case of an optionally performed pH monitoring of the distal esophagus,
- Patients with PPI-responsive esophageal eosinophilia
- Achalasia, scleroderma esophagus, or systemic sclerosis,
- Other clinically evident causes than EoE for esophageal eosinophilia,
- Any concomitant esophageal disease and relevant gastro-intestinal disease (celiac disease, inflammatory bowel disease, oropharyngeal or esophageal bacterial, viral, or fungal infection [candida esophagitis]),
- Any relevant systemic disease (e.g., AIDS, active tuberculosis),
- If careful medical monitoring is not ensured: cardiovascular disease, diabetes mellitus, osteoporosis, active peptic ulcer disease, glaucoma, cataract, or infection,
- Liver cirrhosis or portal hypertension,
- History of cancer in the last five years,
- History of esophageal surgery at any time or of esophageal dilation procedures within the last 8 weeks prior to screening visit,
- Upper gastrointestinal bleeding within 8 weeks prior to screening visit,
- Existing or intended pregnancy or breast-feeding. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Rate of patients with clinico-pathological remission |
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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) |
- Rate of patients with histological remission,
- Change from baseline in histology
- Rate of patients with resolution of symptoms (i.e., no or only minimal problems of EoE). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
6 week open label phase after 6 weeks of treatment for patients not having reached remission |
|
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
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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.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 14 |