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

August 19, 2006
May 25, 2011
February 2004
August 2008   (final data collection date for primary outcome measure)
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 ]
  • We will first confirm that anti-IgE therapy causes a reduction in the
  • in basophil response to cross-linkage of FcRI and then determine whether it also affects basophil response induced by non-IgE stimuli
  • FcRI level on basophils and then analyze whether this occurs at a
  • transcriptional level. We will confirm that the therapy causes a reduction
Complete list of historical versions of study NCT00367016 on ClinicalTrials.gov Archive Site
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 ]
  • We will determine whether anti-IgE therapy results in a suppression of
  • IgE production, in addition to sequestration of IgE.
Not Provided
Not Provided
 
Immunologic Basis of Anti-IgE Therapy (Study II: On Patients With Asthma)
Immunologic Basis of Anti-IgE Therapy (Study II: On Patients With Asthma)

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.

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.
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Asthma
  • Allergic Rhinitis
  • Atopic Dermatitis
  • Drug: Xolair (Omalizumab)
    Xolair (Omalizumab) will be given by subcutaneous injection according to Ige level and weight calculation.
    Other Name: Xolair (Omalizumab)
  • Drug: Placebo
    Placebo
    Other Name: Placebo
  • 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
    Intervention: Drug: 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
    Intervention: Drug: Xolair (Omalizumab)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
7
December 2008
August 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

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

Exclusion Criteria:

  • Other lung diseases
  • Blood clotting disorder
  • Pregnant or lactating women
Both
18 Years to 55 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00367016
200312064-4
No
Fu-Tong Liu, MD, PhD, University of California Davis
University of California, Davis
Not Provided
Principal Investigator: Fu-Tong Liu, MD University of California, Davis
University of California, Davis
May 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP