BUL2/EER
Research type
Research Study
Full title
Double-blind, randomized, placebo-controlled, phase III study on the efficacy and tolerability of a 48-week treatment with two different doses of budesonide effervescent tablets vs. placebo for maintenance of clinico-pathological remission in adult patients with eosinophilic esophagitis
IRAS ID
192865
Contact name
Stephen Attwood
Contact email
Sponsor organisation
Dr. Falk Pharma GmbH
Eudract number
2014-001485-99
Clinicaltrials.gov Identifier
Acronym, EOS-2
Duration of Study in the UK
4 years, 0 months, 1 days
Research summary
Research Summary
Eosinophilic esophagitis (EoE) is an allergic inflammatory condition of the esophagus (also known as the oesophagus or gullet), that involves eosinophils, a type of white blood cell. The disease often presents with dysphagia (difficulty swallowing), food impaction, regurgitation/vomiting, or decreased appetite. Currently EoE is diagnosed by the combination of clinical symptoms of esophageal dysfunction. Most commonly these are dysphagia and chest pain, and the histological finding of at least 15 eosinophils in one high power microscopic field from a tissue sample (biopsy) taken from the lining on the inside surface of the esophagus (the esophageal mucosa) that has been analysed by clinicians. In diagnosis, all clinical and pathologic (disease signs and symptoms) information should be taken into account and should not be interpreted in isolation.Recent studies suggest that swallowing budesonide is highly effective in treating acute EoE. Further, that this might not be associated with toxicities common with the long term use of corticosteroid treatment delivered orally or via intramuscular injection.
During the double-blind phase of the study the primary objective is to assess the efficacy of a 48-week treatment with 2 x 0.5 mg/day or 2 x 1 mg/day budesonide effervescent tablets vs. placebo for the maintenance of remission in adult patients with EoE. During this phase secondary objectives are to study safety and tolerability; and to assess patients’ quality of life.
During the open-label re-induction and open-label extension phase the study will document re-induction of clinical response in patients with a clinical or histological relapse or having experienced a food impaction which needed endoscopic intervention; in addition the study will evaluate the maintenance of clinical remission in patients who completed the double-blind phase without a clinical or histological relapse.
In addition an exploratory objective for the study is to look at biomarkers in EoE.
Summary of Results
Both, BUL 0.5mg (twice daily, BID) and BUL 1mg (twice daily, BID) were significantly superior to placebo for prevention of treatment failure after 48 weeks in adult eosinophilic esophagitis (EoE) patients being at baseline in clinico-pathological remission, Both, BUL 0.5mg BID and BUL 1mg BID prevented histological relapse in more than 80% of all treated patients, indicating that the orodispersible tablet formulations offer an optimal esophageal targeting, In addition, all five a priori ordered key secondary efficacy endpoints proved superiority of BUL 0.5mg BID and BUL 1mg BID versus placebo in a confirmatory manner, Moreover, the superiority observed with the primary and a priori ordered key secondary efficacy endpoints were supported by the superiority of both, BUL 0.5mg BID and BUL 1mg BID to placebo also in all other clinical, histological, endoscopic, and Quality of Life efficacy endpoints, BUL 1mg BID showed consistently better results for bringing and keeping patients in deep disease remission, thereby further minimizing the risk of disease progression in these patients, A 6-week open-label treatment with BUL 1mg BID was highly effective for inducing clinico- histological remission, thereby confirming in a larger number of patients the results obtained under DB treatment with BUL 1mg BID in the BUL-1/EEA (EOS-1) study, A 6-week open-label re-treatment with BUL 1mg BID was safe and highly effective for reinducing clinical remission and improving QoL in patients showing a clinical or histological relapse during the double-blind phase, indicating that recycling treatment of relapsing patients is effective without loss of efficacy, Supporting the results of the 48-week double-blind treatment, an up to 96-weeks open-label treatment with BUL 0.5mg BID (or BUL 1mg BID for patients with dose escalation) was highly effective in preventing clinical, endoscopic, and histological relapse in EoE patients and further improved patient’s quality of life, Deep clinical, histological or endoscopic remission could be maintained over 3 years, indicating that a prolonged maintenance treatment can change the natural course of the disease and can efficiently interrupt the fibrostenotic remodelling process, Maintenance treatment with BUL 1mg BID or BUL 0.5mg BID is highly effective for increasing the esophageal distensibility compared to placebo and thus can stop and even revert a present fibrostenotic remodelling process in the esophagus, Overall, budesonide was well tolerated in this study, The nature and frequency of AEs observed in both budesonide groups and also over an extended treatment period of up to 3-years did not lead to any safety concerns and were consistent with the known safety profile of topical budesonide, Local fungal infection occurred numerically more frequently in the budesonide groups, without showing a dose effect, but was non-serious, in general of mild intensity, mostly did not interfere with normal daily activities, and did not impact the treatment effect even in this up to 3-years maintenance study, Therefore, daily doses of 0.5 mg or 1 mg budesonide orodispersible tablets BID are suitable doses for maintaining of remission in EoE, both with an overall positive benefit/risk ratio.REC name
North East - Newcastle & North Tyneside 2 Research Ethics Committee
REC reference
15/NE/0396
Date of REC Opinion
23 Dec 2015
REC opinion
Favourable Opinion