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

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.

Study Overview

• Status: Completed
• Conditions: Asthma; Allergic Rhinitis; Atopic Dermatitis
• Intervention / Treatment: Drug: Omalizumab; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95816
      • UC Davis Department of Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Omalizumab; Subjects will receive subcutaneous Omalizumab for 6 months. 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: Omalizumab; Xolair (Omalizumab) will be given by subcutaneous injection according to Ige level and weight calculation.; Other Names: Xolair
Experimental: Placebo; Subjects will receive subcutaneous placebo for 6 months. Prior to placebo 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, given by subcutaneous injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FcεRI (High Affinity Receptor) Levels at 3 Months	Skin biopsies were collected from patients after 0 (pre), 3 (pos1) and 6 (pos2) months of omalizumab (P11, P36, P42) or placebo (P7 and P38) treatment. The skin was fixed and the paraffin-embedded sections were stained for high affinity receptors. The average numbers of positively stained cells in each field were counted under a microscope at 400X magnification.	3 months
FcεRI (High Affinity Receptor) Levels at 6 Months	Skin biopsies were collected from patients after 0 (pre), 3 (pos1) and 6 (pos2) months of omalizumab (P11, P36, P42) or placebo (P7 and P38) treatment. The skin was fixed and the paraffin-embedded sections were stained for high affinity receptors. The average numbers of positively stained cells in each field were counted under a microscope at 400X magnification.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Sera IgE Levels at 6 Months	Total sera IgE levels are increased upon anti-IgE treatment. Sera from each patient were collected every month after omalizumab (P11, P36 and P42) or placebo (P7, P37 and P38) treatment. The sera IgE levels were measured by ELISA using polyclonal goat anti-human IgE as the capture antibody and HRP-goat anti-human IgE as the detection antibody.	6 months

Collaborators and Investigators

• Sponsor: University of California, Davis
• Investigators: Principal Investigator: Fu-Tong Liu, M.D., Ph.D., University of California, Davis

Publications and helpful links

Helpful Links

• University of California-Davis Department of Dermatology Clinical Research

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Primary Completion (Actual): October 17, 2012
• Study Completion (Actual): October 17, 2012

Study Registration Dates

• First Submitted: August 19, 2006
• First Submitted That Met QC Criteria: August 19, 2006
• First Posted (Estimate): August 22, 2006

Study Record Updates

• Last Update Posted (Actual): July 13, 2021
• Last Update Submitted That Met QC Criteria: June 21, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Otorhinolaryngologic Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Asthma; Dermatitis; Rhinitis; Rhinitis, Allergic; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Omalizumab
• Other Study ID Numbers: 200312064