Eosinophilic Esophagitis Study
Research type
Research Study
Full title
A Phase 3, Randomized, 3-Part Study to Investigate the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients with Eosinophilic Esophagitis (EoE)
IRAS ID
250792
Contact name
Phillip Woodland
Contact email
Sponsor organisation
Regeneron Pharmaceuticals, Inc.
Eudract number
2018-000844-25
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
136142, IND
Duration of Study in the UK
4 years, 1 months, 27 days
Research summary
Research Summary
This is a clinical research trial to determinate the safety and effectiveness of dupilumab for the treatment of Eosinophilic Esophagitis (EoE). The main purpose is to evaluate the effect of dupilumab on relieving EoE symptoms and reducing oesophageal inflammation. Participants will be adults and adolescents ≥12 years of age with a confirmed diagnosis of EoE.
EoE is the most common cause of food impaction, a painful and distressing condition that can necessitate urgent endoscopic removal of a bolus from the oesophagus. Patients are also at risk of other complications such as perforation of the oesophagus and aspiration into the lungs. There are no approved treatments for EoE; current recommended treatments are dietary management or medications such as steroids to alleviate the symptoms or put EoE into remission.
The study drug dupilumab is a monoclonal antibody. An antibody is a protein that the immune system normally makes to fight bacteria and viruses. Scientists can now make antibodies in the laboratory and produce them for the treatment of different diseases. Dupilumab has been shown to block the action of the proteins called Interleukin 4 (IL-4) and Interleukin 13 (IL-13) which are thought to be involved in the development of inflammatory allergic diseases such as atopic dermatitis (eczema), asthma, and EoE. Dupilumab has been approved for the treatment of moderate to severe atopic dermatitis in adults.Participants for this study will enrol onto Part A or B. Both are randomised, double-blind, and placebo-controlled; they are identical in terms of the schedule of study visits and the procedures performed. Participants will then move on to Part C, an open label study in which all participants will receive the study drug.
This is a commercially funded clinical trial being undertaken by Regeneron Pharmaceuticals, Inc. in 14 countries, with a planned total of 425 participants worldwide.
Summary of Results
A PHASE 3, RANDOMIZED, 3-PART STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF DUPILUMAB IN ADULT AND ADOLESCENT PATIENTS WITH EOSINOPHILIC ESOPHAGITIS
Background: Eosinophilic esophagitis (EoE) is a chronic, inflammatory, allergic mediated disease of the esophagus. The disease is characterized by local inflammation of the esophagus (by an inflammatory cell called an eosinophil. Symptoms of EoE include difficulty swallowing and food impaction (i.g. food getting stuck). There are a significant number of patients who are intolerant to, or who do not get adequate relief from, or who are not suitable candidates to the currently available treatment options for EOE.
Purpose of the study: To determine whether treatment of patients with dupilumab improves the inflammation of the esophagus and improves symptoms of difficulty swallowing in patients with EOE as compared to placebo (dummy treatment).
To determine if treatment with dupilumab is well-tolerated by these patients.
Study participants: This study included 321 male and female patients aged 12 years and older who had previously been treated with other available medications for EOE.
Study design and research methodology:
• This was a multi-national study that enrolled patients at sites in North America, Europe, and Australia
• The patients were randomly divided into a placebo group and dupilumab treatment groups at various dose levels
• The study consisted of a screening period of up to 12 weeks, a 52 week treatment period comprised of a 24 week randomized, double blind, placebo-controlled treatment period and a 28 week extended active treatment period (where all patients received dupilumab) and a 12 week follow up period following the extended active treatment period
• Side-effects were studied
• Endoscopy and biopsies were used to look for changes in the esophagus
• Symptoms were recorded daily on an electronic diary (e-diary) to look for changes in the symptom of difficult swallowingKey findings:
• Patients who were treated with dupilumab weekly showed a larger improvement in the inflammatory changes in esophagus (reduction in the amount of eosinophils) compared with the placebo group during the double-blind placebo-controlled period
• Patients who were treated with dupilumab weekly showed a larger improvement in the structural changes in esophagus for the duration of treatment compared with the placebo group during the double-blind placebo-controlled period
• Patients who were treated with dupilumab weekly showed a larger improvement in symptoms (e.g. difficulty swallowing) and quality of life for the duration of treatment compared with the placebo group during the double-blind placebo controlled period
• The improvements on the inflammatory, structural, and symptomatic components were sustained during the 28-week extended active period (for a total duration of 52 weeks of treatment)
• Patients who received placebo in the double-blind placebo-controlled period achieved large improvements in the inflammatory, structural, and symptomatic components of their disease when they received dupilumab weekly during the 28-week extended active treatment period
• Across all treatment groups, the majority of patients with on-study adverse events experienced events that were mild or moderate in severityREC name
London - Chelsea Research Ethics Committee
REC reference
19/LO/0697
Date of REC Opinion
12 Jul 2019
REC opinion
Further Information Favourable Opinion