Ignite Creation Date:
2024-05-05 @ 6:40 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00523354
Status:
COMPLETED
Last Update Posted:
2009-04-07
First Post:
2007-08-30
Brief Title:
Off Label Use of Infliximab in Adult Patients With Severe Eosinophilic Esophagitis
Sponsor:
Swiss EE Study Group
Organization:
Swiss EE Study Group
Study Overview
Official Title:
Phase 2 Proof-of-Concept Study to Analyze the Efficacy of in TNF-Alpha Blockade in Adult Patients With Severe Corticosteroid-Dependent Eosinophilic Esophagitis
Status:
COMPLETED
Status Verified Date:
2009-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
IEE
Brief Summary:
Eosinophilic Esophagitis EE is a chronic inflammatory disorder of the esophagus with a constantly increasing prevalence It has been demonstrated that the expression of the cytokine TNF-α is up regulated in EE and that this pro-inflammatory cytokine is highly expressed by the keratinocytes of the esophageal epithelium in patients with active EE Furthermore it has been shown that TNF-α is capable to induce eotaxin-3 production in keratinocytes These results suggest that TNF-α plays a crucial role in the pathogenesis of EE Based on these findings the investigators plan a prospective T1 translational study with the purpose to evaluate the efficacy of an Infliximab monotherapy in adult patients with severe corticosteroid-dependent EE
Detailed Description:
Study Principle An open-conducted un-controlled off label use of Infliximab will be performed in at least 3 individuals with Eosinophilic Esophagitis EE to evaluate the efficacy of an TNF-α blockade in the treatment of adult patients with severe isolated EE
Rationale for this Trial Eosinophilic Esophagitis is a chronic TH2-type dominant inflammatory disorder of the esophagus with a constantly increasing prevalence It has been demonstrated that the cytokines TNF-α and IL-5 as well as the chemokine eotaxin-3 play a crucial role in the immuno-pathogenesis of this disease These mediators are potential targets for therapeutic interventions The established diagnostic criteria of EE are PPI-resistent esophageal related symptoms in combination with an infiltration of the esophageal mucosa with more than 20 eosinophilshpf a tissue where eosinophils are not normally encountered
Treatment strategies in chronic inflammations have basically two goals 1 Relief of symptoms and 2 Prevention of long-term damage of the affected organ due to a persistence of an uncontrolled inflammation Standard recommendations for medical therapy of EE include systemic or topical corticosteroids and leukotriene antagonists The treatment with corticosteroids is limited by the occurence of steroid-dependence and steroid-resistance as well as the corticosteroid adherent side effects
Infliximab a chimeric monoclonal IgG antibody is a potent inhibitor of the soluble and the membrane-bound form of TNF-α Its efficacy in inducing and maintaining a remission in several TH1- and TH2-type inflammations is well documented Infliximab is since more than 5 years approved for the therapy of these immune-mediated inflammations Today it is used as standard therapy in a subset of severe forms in these disorders Meanwhile an overwhelming mass of data has confirmed the efficacy and the safety of this compound
Purpose of this StudyThe purpose of this pilot-trial is to evaluate the efficacy of a TNF-α blockade with Infliximab monotherapy as induction-treatment in adult patients with severe EE
Rationale for this Trial Eosinophilic Esophagitis is a chronic TH2-type dominant inflammatory disorder of the esophagus with a constantly increasing prevalence It has been demonstrated that the cytokines TNF-α and IL-5 as well as the chemokine eotaxin-3 play a crucial role in the immuno-pathogenesis of this disease These mediators are potential targets for therapeutic interventions The established diagnostic criteria of EE are PPI-resistent esophageal related symptoms in combination with an infiltration of the esophageal mucosa with more than 20 eosinophilshpf a tissue where eosinophils are not normally encountered
Treatment strategies in chronic inflammations have basically two goals 1 Relief of symptoms and 2 Prevention of long-term damage of the affected organ due to a persistence of an uncontrolled inflammation Standard recommendations for medical therapy of EE include systemic or topical corticosteroids and leukotriene antagonists The treatment with corticosteroids is limited by the occurence of steroid-dependence and steroid-resistance as well as the corticosteroid adherent side effects
Infliximab a chimeric monoclonal IgG antibody is a potent inhibitor of the soluble and the membrane-bound form of TNF-α Its efficacy in inducing and maintaining a remission in several TH1- and TH2-type inflammations is well documented Infliximab is since more than 5 years approved for the therapy of these immune-mediated inflammations Today it is used as standard therapy in a subset of severe forms in these disorders Meanwhile an overwhelming mass of data has confirmed the efficacy and the safety of this compound
Purpose of this StudyThe purpose of this pilot-trial is to evaluate the efficacy of a TNF-α blockade with Infliximab monotherapy as induction-treatment in adult patients with severe EE
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None