Identifying Responders to Xolair (Omalizumab) Using Eosinophilic Esophagitis as a Disease Model

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
O & O Alpan LLC
ClinicalTrials.gov Identifier:
NCT01040598
First received: December 27, 2009
Last updated: March 13, 2012
Last verified: March 2012
  Purpose

Eosinophilic Esophagitis(EoE) is a condition characterized commonly by vomiting, nausea, epigastric pain, dysphagia, heartburn and food impaction among other gastrointestinal symptoms along with obstructive esophageal symptoms in both pediatric and adult population. The pathology of this disease is postulated to be allergy mediated and the incidence of this disease is seen to parallel an increase in the incidence of allergies and asthma.

Most of the current therapies for EoE are directed at decreasing esophageal allergic inflammation and mirror the treatment options for allergic asthma. Swallowed corticosteroids and elimination diets or elemental diets have shown variable efficacy is improving symptoms. However, specific pathophysiologic mechanism of EoE is still largely unknown and there is no definitive treatment that completely resolves symptoms and histological findings. Omalizumab is a recently developed anti-IgE antibody that has been shown to decrease the use of inhaled and oral corticosteroids and improve asthma related symptoms in patients with allergic asthma. In this study, Eosinophilic esophagitis is being used as a disease model to study the mechanism of action of monoclonal Anti-IgE antibody in vivo. The resolution of symptoms clinically, and histological changes (and improvements) in response to treatment with Xolair (omalizumab) in patients suffering from EoE will be determined. The primary objective of this open label, study is to determine mucosal markers that will predict responders to Omalizumab (Xolair).


Condition Intervention Phase
Eosinophilic Esophagitis
Biological: Omalizumab
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Identifying Responders to Xolair (Omalizumab) Using Eosinophilic Esophagitis as a Disease Model

Resource links provided by NLM:


Further study details as provided by O & O Alpan LLC:

Primary Outcome Measures:
  • Our primary objective is to determine markers that will predict responders to Omalizumab(Xolair) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Secondary objectives will be determining the immunological changes in the tissue before and after treatment with Xolair (omalizumab) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 19
Study Start Date: June 2009
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: Omalizumab
    Omalizumab, an anti-IgE monoclonal antibody is dosed on the basis of subject's weight and IgE levels. It is administered as a subcutaneous injection every 2 weeks or 4 weeks based on the total dose required.
    Other Name: Xolair
Detailed Description:

This is an open label mechanistic study to learn about the effect of Omalizumab on the clinical symptoms and immunohistological findings in established cases of EoE. The dosage for Omalizumab will be based on patient's body weight and baseline IgE level. Omalizumab will be administered subcutaneously every 2 or 4 weeks for total duration of 12 weeks. At enrollment, subjects will have EGD with biopsies performed to confirm diagnosis of EoE and further histologic analysis and special staining. Blood will be drawn for baseline testing and monthly for safety labs. At the end of the 12 week period, repeat endoscopy will be performed and biopsies taken to stain again for various mucosal markers like IgE, IL-13, IL-5 and Tryptase. The patients will be followed for response to therapy with regards to resolution of symptoms and improvement in histology findings on biopsy.

  Eligibility

Ages Eligible for Study:   12 Years to 76 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  • Established diagnosis of eosinophilic esophagitis, determined by eosinophils >15/high power field in the distal esophagus and/or microabscesses.
  • Patients should be on therapy either by food avoidance or swallowed steroids, with no change in the food avoidance and steroid dose during therapy.
  • One active symptom of disease (epigastric pain, vomiting, nausea, dysphagia or heartburn) at least 2 days of the week.
  • Failed response to proton pump inhibitors or a negative ph probe test or Negative impedance study.
  • Males and females between ages 12-76 years.

Exclusion criteria

  • Patients with gastrointestinal reflux disease.
  • Eosinophilic disease in the stomach or duodenum.
  • Peripheral eosinophil counts >1500 (hyper eosinophilic syndrome).
  • Women of childbearing potential not using two forms of contraception method(s) including but not limited to condoms, diaphragm, oral contraceptive pills, other hormonal methods, intrauterine device or tubal ligation and vasectomy, as well as women who are breastfeeding
  • Known sensitivity to study drug(s) or class of study drug(s).
  • Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study (specify as required).
  • Use of any other investigational agent in the last 30 days.
  • Use of systemic or inhaled steroids within the past 1 month.
  • History of malignancy.
  • Require chronic immunosuppressive therapy including cyclosporine, methotrexate, etc.
  • Have been treated with Xolair within the 12 months prior to screening.
  • Patients with eosinophilic esophagitis in remission on swallowed steroids.
  • Patients with asthma taking inhaled steroids.
  • Serum IgE levels < 30 IU/l or > 700 IU/l
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01040598

Locations
United States, Virginia
O & O Alpan LLC
Springfield, Virginia, United States, 22152
Sponsors and Collaborators
O & O Alpan LLC
Genentech
Investigators
Principal Investigator: Oral Alpan, MD O & O Alpan LLC
  More Information

No publications provided

Responsible Party: O & O Alpan LLC
ClinicalTrials.gov Identifier: NCT01040598     History of Changes
Other Study ID Numbers: EE001
Study First Received: December 27, 2009
Last Updated: March 13, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by O & O Alpan LLC:
Eosinophilic Esophagitis
Xolair
Omalizumab
Esophagitis
Eosinophils
monoclonal antibody

Additional relevant MeSH terms:
Esophagitis
Eosinophilic Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Antibodies, Monoclonal
Omalizumab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Allergic Agents
Therapeutic Uses
Anti-Asthmatic Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on August 21, 2014