Immunologic Basis of Anti-IgE Therapy (Study II: On Patients With Asthma) (Xolair)

This study has been completed.
Sponsor:
Information provided by:
University of California, Davis
ClinicalTrials.gov Identifier:
NCT00367016
First received: August 19, 2006
Last updated: May 25, 2011
Last verified: May 2011
  Purpose

The purpose of this study is to look at measures that will help scientists understand the way Omalizumab, an FDA-approved anti-allergy medication, works.


Condition Intervention Phase
Asthma
Allergic Rhinitis
Atopic Dermatitis
Drug: Xolair (Omalizumab)
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Immunologic Basis of Anti-IgE Therapy (Study II: On Patients With Asthma)

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • We will first confirm that anti-IgE therapy causes a reduction in the FcεRI level on basophils and then analyze whether this occurs at a transcriptional level. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • We will determine whether anti-IgE therapy results in a suppression of IgE production, in addition to sequestration of IgE. [ Time Frame: 2 Years ] [ Designated as safety issue: No ]

Enrollment: 7
Study Start Date: February 2004
Study Completion Date: December 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: A
The subjects will be randomized to a treatment group and a placebo group. Prior to Omalizumab administration, all subjects will undergo screening studies, including spirometry, blood test and skin test. Blood test includes comprehensive metabolic panel, CBC, and total and free IgE levels. Skin test will be done with a panel of 7 common allergens
Drug: Placebo
Placebo
Other Name: Placebo
Active Comparator: B
The subjects will be randomized to a treatment group and a placebo group. Prior to Omalizumab administration, all subjects will undergo screening studies, including spirometry, blood test and skin test. Blood test includes comprehensive metabolic panel, CBC, and total and free IgE levels. Skin test will be done with a panel of 7 common allergens
Drug: Xolair (Omalizumab)
Xolair (Omalizumab) will be given by subcutaneous injection according to Ige level and weight calculation.
Other Name: Xolair (Omalizumab)

Detailed Description:

IgE is a key molecule involved in immediate hypersensitivity and plays a major role in the pathogenesis of allergic diseases. Recently, a therapy based on the use of anti-IgE antibody has been developed by a pharmaceutical company, Genentech. A number of clinical trials have demonstrated that these antibodies are efficacious in treatment of allergies, including allergic rhinitis and asthma. The medication Omalizumab (Xolair) has recently been approved by the FDA for treatment of asthma.

The mechanism underlying the beneficial effect of this therapy is not completely understood, but is likely to be related to the marked reduction in the IgE level. Of note is the concomitant accumulation of IgE-anti-IgE complexes in the sera. Another remarkable effect of the treatment is the substantial reduction in the FcεRI level on basophils, which is likely a key factor contributing to the therapeutic benefit of the drug. The existing literature suggests that the reduction in the IgE level is likely to result in a down-regulation of another IgE receptor, FcεRII/CD23. Because of the known immunomodulatory function of FcεRII, anti-IgE therapy may result in alterations of the immune system, in addition to simple absorption of IgE.

We propose to conduct mechanistic studies of anti-IgE therapy. The objectives are to address how anti-IgE therapy works and how it might affect the immune system in general. The proposed studies also take advantage of this well-defined therapy to address some basic questions regarding the immune system. Our hypothesis is that anti-IgE therapy may have general effects on the immune system, such as reduced IgE-mediated antigen presentation by antigen-presenting cells and suppressed allergen-specific IgE and IgG production. The specific aims of the proposed research are:

  1. Determination of the effect of anti-IgE therapy on FcεRI expression and basophil responses. We will first confirm that anti-IgE therapy causes a reduction in the FcεRI level on basophils and then analyze whether this occurs at a transcriptional level. We will confirm that the therapy causes a reduction in basophil response to cross-linkage of FcεRI and then determine whether it also affects basophil response induced by non-IgE stimuli. The effect of the therapy on the FcεRI level on skin mast cells will also be investigated.
  2. Determination of the effect of anti-IgE therapy on FcεRII expression and antigen presentation. We will determine whether the therapy results in a down-regulation of FcεRII/CD23 on B cells. Because of the demonstrated function of FcεRII/CD23 in antigen presentation, we will determine the antigen presentation to T cells by B cells from anti-IgE-treated and control subjects.
  3. Determination of the effect of anti-IgE therapy on antibody production. We will determine whether anti-IgE therapy results in a suppression of IgE production, in addition to sequestration of IgE. Whether IgE-anti-IgE complexes directly suppress IgE production by B cells in vitro will be investigated.
  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Mild or moderate persistent asthma
  • Allergic rhinitis
  • Atopic dermatitis

Exclusion Criteria:

  • Other lung diseases
  • Blood clotting disorder
  • Pregnant or lactating women
  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: NCT00367016

Locations
United States, California
University of California, Davis Department of Dermatology
Sacramento, California, United States, 95816
Sponsors and Collaborators
University of California, Davis
Investigators
Principal Investigator: Fu-Tong Liu, MD University of California, Davis
  More Information

Additional Information:
No publications provided

Responsible Party: Fu-Tong Liu, MD, PhD, University of California Davis
ClinicalTrials.gov Identifier: NCT00367016     History of Changes
Other Study ID Numbers: 200312064-4
Study First Received: August 19, 2006
Last Updated: May 25, 2011
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Asthma
Dermatitis
Dermatitis, Atopic
Rhinitis
Rhinitis, Allergic, Perennial
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Nose Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Omalizumab
Anti-Allergic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on August 26, 2014