Off Label Use of Infliximab in Adult Patients With Severe Eosinophilic Esophagitis (IEE)

Phase 2 Proof-of-Concept Study to Analyze the Efficacy of in TNF-Alpha Blockade in Adult Patients With Severe, Corticosteroid-Dependent Eosinophilic Esophagitis

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.

Study Overview

• Status: Completed
• Conditions: Esophagitis
• Intervention / Treatment: Drug: Infliximab

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 eosinophils/hpf, 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 Study:The 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 Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • SO
    • Olten, SO, Switzerland, 4600
      • EE-Clinics, Praxis Roemerhof

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients with severe, corticosteroid-dependent eosinophilic esophagitis

Exclusion Criteria:

• Pregnancy
• Evidence of latent or active tuberculosis
• Other contra-indications for TNF-alpha blockers
• Unstable medical conditions
• Malignancies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1 (open-label); prospective, open label, uncontrolled trial	Drug: Infliximab; Induction therapy with 2 infusions, each 5 mg/kg body weight within 2 wks; Other Names: Remicade

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Tissue eosinophilia before and after therapy

Collaborators and Investigators

• Sponsor: Swiss EE Study Group
• Investigators: Study Chair: Hans-Uwe Simon, MD and PhD, Deaprtment of Pharmacology, University Bern, Bern, Switzerland

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (ACTUAL): September 1, 2007
• Study Completion (ACTUAL): October 1, 2007

Study Registration Dates

• First Submitted: August 30, 2007
• First Submitted That Met QC Criteria: August 30, 2007
• First Posted (ESTIMATE): August 31, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): April 7, 2009
• Last Update Submitted That Met QC Criteria: April 6, 2009
• Last Verified: April 1, 2009

More Information

Terms related to this study

• Keywords: Eosinophilic Esophagitis; Infliximab; TNF-alpha; TNF-alpha Blockade
• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Gastrointestinal Diseases; Gastroenteritis; Hypersensitivity; Esophageal Diseases; Leukocyte Disorders; Eosinophilia; Eosinophilic Esophagitis; Esophagitis; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Infliximab
• Other Study ID Numbers: Swiss EE-Study Group