Correlation Between IgE Parameters and the Response to Omalizumab in Subjects With Severe Asthma (OM-2009-XO)

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by:
Carmel Medical Center
ClinicalTrials.gov Identifier:
NCT01002976
First received: October 25, 2009
Last updated: January 23, 2012
Last verified: January 2012
  Purpose

Omalizumab is an anti-IgE recombinant humanized monoclonal antibody.The efficacy and tolerability of omalizumab have been demonstrated in patients with moderate-to-severe and allergic (IgE-mediated) asthma. Clinical benefit with omalizumab is observed when serum free IgE levels are reduced to 50 ng/mL or less. However, although the causal role of IgE in allergic disease is well established, the relationship between free IgE and clinical symptoms of asthma has not been accurately quantified. Recent study demonstrated that omalizumab and free IgE concentrations are correlated with clinical outcomes. In non responder to omalizumab the clinical symptoms show random fluctuations around baseline without any tendency toward improvement despite adequate suppression of free IgE. In these patients it may be the ratio of specific IgE to total IgE or inter-patient variability in the expression of FceRI on effector cells that define whether the patient will respond or not to omalizumab.

This current study is designed to evaluate the mechanisms of responsiveness to omalizumab measuring the free IgE, specific IgE and the level of FceRI expression on the effector cell and the correlation to clinical response.


Condition Phase
Severe Allergic Asthma
Phase 4

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Correlation Between Level of Free IgE, Total IgE, Specific IgE and FceRI Expression on Effectors Cells and the Respond to Omalizumab in Subjects With Severe Asthma. Single Arm Open Label Study

Resource links provided by NLM:


Further study details as provided by Carmel Medical Center:

Primary Outcome Measures:
  • Rate of clinically significant asthma exacerbation (defined as worsening of symptoms requiring systemic steroids treatment) [ Time Frame: 4-6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Forced Vital Capacity (FVC) [ Time Frame: 4-6 months ] [ Designated as safety issue: No ]
  • FEV1/FVC ratio [ Time Frame: 4-6 months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Blood Sputum


Enrollment: 0
Study Start Date: December 2009
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Detailed Description:

Omalizumab represents a new therapeutic approach for IgE-mediated disease. Omalizumab is an anti-IgE recombinant humanized monoclonal antibody designed to treat IgE-mediated disease by reducing the concentration of free IgE antibody in subjects.

The safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses of Omalizumab have now been studied in more than 2000 patients. Omalizumab compared to placebo has been demonstrated to reduce the number of asthma exacerbations, reduce the concomitant medication burden, improve the symptom severity and improve quality of life in phase III studies in the treatment of patients with allergic asthma, perennial allergic rhinitis and seasonal allergic rhinitis. For further information the reader is referred to the investigator brochure.

Allergic (IgE-mediated) asthma is characterized by the presence of IgE antibodies against common allergens. When allergen cross-links specific IgE bound to high-affinity IgE (FceRI) receptors on the surface of basophils and mast cells, proinflammatory mediators are released that trigger and perpetuate airway symptomatology. Omalizumab, an anti-IgE mAb, binds to the Fc region of all forms of circulating IgE, regardless of IgE specificity, preventing IgE-mediated responses, and downregulating FceRI expression on mast cells and basophils. The efficacy and tolerability of omalizumab have been demonstrated in patients with moderate-to-severe (IgE-mediated) asthma. Clinical benefit with omalizumab is observed when serum free IgE levels are reduced to 50 ng/mL or less. Omalizumab dosing is based on pretreatment total serum IgE level and body weight, and calculated using a dosing table. Omalizumab binds to IgE to reversibly form IgG-IgE complexes. In binding, omalizumab pushes the reaction toward the IgG-IgE complex, which is incapable of binding to IgE receptors, thereby suppressing free IgE and reducing the clinical symptoms of allergic asthma. However, although the causal role of IgE in allergic disease is well established, the relationship between free IgE and clinical symptoms of asthma has not been accurately quantified. Recent study demonstrated that omalizumab and free IgE concentrations are correlated with clinical outcomes. In non responder to omalizumab the clinical symptoms show random fluctuations around baseline without any tendency toward improvement despite adequate suppression of free IgE. In these patients it may be the ratio of specific IgE to total IgE or inter-patient variability in the expression of FceRI on effector cells that define whether the patient will respond or not to omalizumab.

This current study is designed to evaluate the mechanisms of responsiveness to omalizumab measuring the free IgE, specific IgE and the level of FceRI expression on the effector cell and the correlation to clinical response.

To further characterize the patients' phenotype we will also evaluate fraction of Nitric Oxide in expired air (FE-NO) levels and eosinophils percentage in induced sputum before and at the end of the study.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

male and female subjects with allergic asthma, aged 18-75 years that, based on standard practice, have been assigned to omalizumab treatment and fulfill all requirements for such treatment will be included in this study

Criteria

Inclusion Criteria:

  • Subjects who (or as appropriate whose legal guardian) have been informed of the study procedures and medications and have given their written informed consent
  • Subjects with severe allergic asthma that based on standard practice have been assigned to omalizumab treatment and fulfill all requirements for such treatment
  • The requirements include:

    • Uncontrolled severe asthma despite maximal and optimal therapy , GINA stage IV
    • Reversible airway obstruction ( a change of 12% of FEV1 after bronchodilator inhalation)
    • Non smoking or smoking less then 10 PY.
    • Positive skin test or RAST test for relevant allergen
    • IGE blood level between 30-700 IU and
    • Two or more asthma exacerbation needed systemic steroids treatment during the last twelve months or continuing systemic steroid treatment. or
    • Contraindication to systemic steroid treatment due to side effects, such as osteoporosis and uncontrolled diabetes.

Exclusion Criteria:

  • Pregnancy or nursing mothers
  • Subject who have experienced a severe hypersensitivity reaction to Xolair®
  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: NCT01002976

Locations
Israel
Carmel Medical Center
Haifa, Israel
Sponsors and Collaborators
Carmel Medical Center
Investigators
Principal Investigator: Yochai Adir, MD Carmel Medical Center
  More Information

No publications provided

Responsible Party: Adir Yochai, MD, Carmel Medical Center
ClinicalTrials.gov Identifier: NCT01002976     History of Changes
Other Study ID Numbers: CMC-09-0065-CTIL
Study First Received: October 25, 2009
Last Updated: January 23, 2012
Health Authority: Israel: Ministry of Health

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on September 18, 2014