Primary:* To assess the efficacy of 2 x 1 mg/d budesonide effervescent tablets vs. placebo for the induction of clinico-pathological remission in adult patients with active eosinophilic esophagitis (EoE).Secondary:* To study safety and tolerability…
ID
Source
Brief title
Condition
- Gastrointestinal infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Rate of patients with clinico-pathological remission at week 6 (LOCF) defined
as fulfilling both criteria:
- Histological remission, i.e., peak of <16 eos/mm2 hpf at week 6 (LOCF), AND
- Resolution of symptoms (i.e., no or only minimal problems) defined as a
severity of *2 points on 0 to 10-point (0-10) NRS for dysphagia AND
a severity of *2 points on 0-10 NRS for pain during swallowing on
each day in the week prior to week 6 (LOCF).
Secondary outcome
A priori ordered key secondary endpoints (DB-phase):
1. Rate of patients with histological remission, defined as a peak of <16
eos/mm2 hpf at week 6 (LOCF),
2. Change in the peak eos/mm2 hpf from baseline to week 6 (LOCF),
3. Rate of patients with resolution of symptoms (i.e., no or only minimal
problems) defined as a severity of *2 points on 0-10 NRS for dysphagia AND a
severity of *2 points on 0-10 NRS for pain during swallowing on each day in the
week prior to week 6 (LOCF),
4. Rate of patients with total weekly Eosinophilic Esophagitis Activity Index *
Patient-Reported Outcome (EEsAI-PRO) score of *20 at week 6 (LOCF),
5. Rate of patients with an improvement from baseline to week 6 (LOCF) in the
weekly Visual Dysphagia Question (VDQ) score,
6. Rate of patients with an improvement from baseline to week 6 (LOCF) in the
weekly *Avoidance, Modification, and Slow-eating (AMS) score.
Background summary
Recent studies suggest that swallowing of budesonide is highly effective in the
treatment of EoE, and might not be associated with the toxicities of long term
use of systemic corticosteroids.
Study objective
Primary:
* To assess the efficacy of 2 x 1 mg/d budesonide effervescent tablets vs.
placebo for the induction of clinico-pathological remission in adult patients
with active eosinophilic esophagitis (EoE).
Secondary:
* To study safety and tolerability in the form of adverse events and laboratory
parameters,
* To assess patients* quality of life.
Study design
This is a double-blind, randomized, multicenter, placebo-controlled,
compara-tive, confirmatory Phase III clinical trial.
Intervention
The trial will be conducted with two treatment groups in the form of a parallel
group comparison and will serve to compare oral treatment with 2 x 1 mg/d
budesonide effervescent tablets vs. placebo for the treatment of active EoE.
The up to 6-week screening period will be followed by a 6-week double-blind
(DB) treatment period and an optional 6-week open-label induction (OLI)
treatment with 2 x 1 mg/d budesonide effervescent tablets in patients eligible
for OLI-treatment (e.g., clinico-pathological non-remitters), and a 4-week
follow-up period (if the patient will not further continue in the program).
Study burden and risks
physical examination 3-6x
endoscopy of the oesophagus 2-3x
questionnaire related to complaints and disease: 8 questionnaires, per
questionnaire variable 6-10x
blood sampling 4-7x
urine sampling 5-8 x
in total 6-10 visits.
The adverse events are characteristic for steroid medication, and can occur
depending on the dosage, treatement period, whether the subject is or has been
taking other corticosteroid preparations, and the individual sensitivity.
Leinenweberstrasse 5
Freiburg 79108
DE
Leinenweberstrasse 5
Freiburg 79108
DE
Listed location countries
Age
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
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-001484-12-NL |
| ClinicalTrials.gov | NCT02434029 |
| CCMO | NL54155.041.15 |