The Effect of Omalizumab on Responses to Cat Allergen Challenge

NCT ID: NCT00604786

Last Updated: 2017-05-10

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-07-31

Study Completion Date

2009-01-31

Brief Summary

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This research is being done to study the effects of the drug omalizumab (Xolair) in people with cat allergies. The investigators will use omalizumab to study changes in the cells in the nose, skin and blood that cause allergies. The investigators predict that cells in the blood will be effected before cells in the nose or skin.

Detailed Description

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Omalizumab is a monoclonal antibody directed against Immunoglobulin E (IgE) and is FDA-approved for use in allergic asthma, though its clinical role is not precisely defined. It binds IgE on the same site of the Fc domain as the high affinity IgE receptor (FcεRI), and therefore, blocks the interaction between IgE and mast cells or basophils. It, therefore, may be used as a mechanistic tool in the study of IgE. As IgE levels are reduced with omalizumab, FcεRI expression on human basophils is reduced. This reduction of basophil receptors and allergen induced activation is pronounced within 7 days of the initial administration and is reversible once omalizumab administration is discontinued. The omalizumab-induced reductions in mast cell FcεRI expression and function is unchanged at day 7 and significantly reduced by day 70. These changes were based upon intravenously administered omalizumab at a dose of 0.03 mg/kg/IU IgE/mL in a total of three subjects. We propose to exploit the kinetics of faster omalizumab effects on circulating basophils relative to tissue mast cells to elucidate the role of the basophil versus mast cell activation in nasal airway allergen challenge, which has not been studied to date.

Conditions

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Allergic Rhinitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Omalizumab subcutaneous

This active are will receive treatment with omalizumab subcutaneously at the dose currently FDA-approved for the treatment of allergic asthma. There is a weight and IgE based dosing table in the and subjects receive therapy by subcutaneous injection every 2 or 4 weeks. The lower range of dosing is 150 mg q 4weeks ( one injection) with the upper range 375 mg every 2 weeks ( three injections).

The dosing is based on IgE levels and IGE and is given by subcutaneous injection every 2 to 4 weeks

Group Type EXPERIMENTAL

omalizumab

Intervention Type DRUG

Dosing is based on IgE level and weight given every 2 or 4 weeks

Placebo Subcutaneous

This placebo arm will receive identical treatment with placebo injections subcutaneously at the dose currently FDA-approved for the treatment of allergic asthma. There is a weight and IgE based dosing table in the and subjects receive therapy by subcutaneous injection every 2 or 4 weeks. The lower range of dosing is 150 mg q 4weeks ( one injection) with the upper range 375 mg every 2 weeks ( three injections).

The dosing is based on IgE levels and IGE and is given by subcutaneous injection every 2 to 4 weeks.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Dosing is based on IgE level and weight given every 2 or 4 weeks

Interventions

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omalizumab

Dosing is based on IgE level and weight given every 2 or 4 weeks

Intervention Type DRUG

placebo

Dosing is based on IgE level and weight given every 2 or 4 weeks

Intervention Type DRUG

Other Intervention Names

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Xolair

Eligibility Criteria

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Inclusion Criteria

* Ability to understand and provide informed consent
* Male or Female (non-pregnant), age 18-50
* Females must be: Surgically sterile (hysterectomy, bilateral oophorectomy, bilateral tubal ligation), OR postmenopausal (at least 1 year since last menses), OR using a medically acceptable form of birth control throughout the duration of the study.
* Clinical history of seasonal or perennial allergic rhinitis for at least two years, with or without mild persistent asthma
* Positive puncture skin test greater than or equal to 5 mm diluent control
* Positive Immunocap to Fel d 1 \> 0.35 kallikrein unit/L
* Positive intranasal cat allergen challenge as defined by \> 5 sneezes or a tripling of measured nasal lavage mediators
* In vitro assay of basophil responsiveness to cat allergen with greater than 20% histamine release
* The use of antihistamines, cromolyn, leukotriene modifiers and other non-steroid (astelin and topical decongestants), nasal medications will be allowed, but they will be withheld for 5 days prior to each nasal allergen provocation session. Inhaled corticosteroids for mild asthma will be permissible.
* No known contraindications to therapy with omalizumab

Exclusion Criteria

* Asthma with forced expiratory volume at one second (FEV1) \< 80%, moderate to severe asthma classification per National Asthma Education and Prevention Program Expert Panel (NAEP) Standards (1997 National Asthma Education and Prevention Program Expert Panel Report II guidelines)
* Serum IgE levels less than 30 IU/mL or greater than 700 IU/mL at the time of enrollment will be excluded
* Unexplained elevation of erythrocyte sedimentation rate (ESR), hematocrit \< 32%, white blood cell (WBC) count 2400/microliter lower limit of normal, platelet \< 75000/microliter, creatinine \> 141.4 micromolar/L, or aspartate aminotransferase (AST) \> 100 IU/L
* Body weight less than 30 kg or greater than 150 kg will be excluded.
* Plans to become pregnant or breastfeed will be excluded from the study
* A perforated nasal septum, structural nasal defect, large nasal polyps causing obstruction, evidence of acute or chronic sinusitis
* A life expectancy less than 6 months
* A terminal illness as determined by the investigator
* A history of malignancy, anaphylaxis or bleeding disorder are also exclusion illnesses.
* Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.
* Inability or unwillingness of a participant to give written informed consent or comply with study protocol
* Use of any investigational drugs within 8 weeks of participation
* Contraindications to omalizumab include patients with a previous hypersensitivity to omalizumab
* Recent recipient of any licensed or investigational live attenuated vaccine(s) within two months of study initiation such as flu mist.
* Prior use of omalizumab
* Frequent sinusitis (\>2/ documented episodes per year) or active sinusitis within 2 weeks of enrollment
* Use of immunotherapy within the last 5 years
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sarbjit S Saini, M.D.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

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Johns Hopkins Asthma and Allergy Center

Baltimore, Maryland, United States

Site Status

Countries

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United States

References

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Other Identifiers

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U19AI070345

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NA_00007520

Identifier Type: -

Identifier Source: org_study_id

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