The Effect of Omalizumab on Responses to Cat Allergen Challenge

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ClinicalTrials.gov Identifier: NCT00604786

Recruitment Status : Completed

First Posted : January 30, 2008

Results First Posted : April 4, 2017

Last Update Posted : May 10, 2017

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

National Institute of Allergy and Infectious Diseases (NIAID)

Information provided by (Responsible Party):

Johns Hopkins University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Allergic Rhinitis	Drug: omalizumab Drug: placebo	Not Applicable

Detailed Description:

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	18 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Basic Science
Official Title:	Pilot Study of the Effect of Omalizumab on Basophil and Mast Responses to Intranasal Cat Allergen Challenge
Study Start Date :	July 2007
Actual Primary Completion Date :	January 2009
Actual Study Completion Date :	January 2009

Resource links provided by the National Library of Medicine

Drug Information available for: Omalizumab

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	Drug: omalizumab Dosing is based on IgE level and weight given every 2 or 4 weeks Other Name: Xolair
Placebo Comparator: 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.	Drug: placebo Dosing is based on IgE level and weight given every 2 or 4 weeks

Arm

Intervention/treatment

Experimental: 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

Drug: omalizumab

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

Other Name: Xolair

Placebo Comparator: 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.

Drug: placebo

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

Outcome Measures

Primary Outcome Measures :

Change in Basophil Surface IgE [ Time Frame: Change from baseline to 3.5 months ]
Flow cytometry in mean fluorescence units.

100%*[(3.5 month value minus baseline value)/baseline value]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 50 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00604786

Locations

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United States, Maryland
Johns Hopkins Asthma and Allergy Center
Baltimore, Maryland, United States, 21224

Sponsors and Collaborators

Johns Hopkins University

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

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Principal Investigator:	Sarbjit S Saini, M.D.	Johns Hopkins University

More Information

Additional Information:

Study contact information This link exits the ClinicalTrials.gov site

Publications:

Strunk RC, Bloomberg GR. Omalizumab for asthma. N Engl J Med. 2006 Jun 22;354(25):2689-95. doi: 10.1056/NEJMct055184. No abstract available.

Presta LG, Lahr SJ, Shields RL, Porter JP, Gorman CM, Fendly BM, Jardieu PM. Humanization of an antibody directed against IgE. J Immunol. 1993 Sep 1;151(5):2623-32.

Schulman ES. Development of a monoclonal anti-immunoglobulin E antibody (omalizumab) for the treatment of allergic respiratory disorders. Am J Respir Crit Care Med. 2001 Oct 15;164(8 Pt 2):S6-11. doi: 10.1164/ajrccm.164.supplement_1.2103025.

MacGlashan DW Jr, Bochner BS, Adelman DC, Jardieu PM, Togias A, McKenzie-White J, Sterbinsky SA, Hamilton RG, Lichtenstein LM. Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody. J Immunol. 1997 Feb 1;158(3):1438-45.

Saini SS, MacGlashan DW Jr, Sterbinsky SA, Togias A, Adelman DC, Lichtenstein LM, Bochner BS. Down-regulation of human basophil IgE and FC epsilon RI alpha surface densities and mediator release by anti-IgE-infusions is reversible in vitro and in vivo. J Immunol. 1999 May 1;162(9):5624-30.

Beck LA, Marcotte GV, MacGlashan D, Togias A, Saini S. Omalizumab-induced reductions in mast cell Fce psilon RI expression and function. J Allergy Clin Immunol. 2004 Sep;114(3):527-30. doi: 10.1016/j.jaci.2004.06.032.

Proud D, Bailey GS, Naclerio RM, Reynolds CJ, Cruz AA, Eggleston PA, Lichtenstein LM, Togias AG. Tryptase and histamine as markers to evaluate mast cell activation during the responses to nasal challenge with allergen, cold, dry air, and hyperosmolar solutions. J Allergy Clin Immunol. 1992 Jun;89(6):1098-110. doi: 10.1016/0091-6749(92)90293-b.

Nathan RA, Eccles R, Howarth PH, Steinsvag SK, Togias A. Objective monitoring of nasal patency and nasal physiology in rhinitis. J Allergy Clin Immunol. 2005 Mar;115(3 Suppl 1):S442-59. doi: 10.1016/j.jaci.2004.12.015.

Naclerio RM, Proud D, Togias AG, Adkinson NF Jr, Meyers DA, Kagey-Sobotka A, Plaut M, Norman PS, Lichtenstein LM. Inflammatory mediators in late antigen-induced rhinitis. N Engl J Med. 1985 Jul 11;313(2):65-70. doi: 10.1056/NEJM198507113130201.

Lin H, Boesel KM, Griffith DT, Prussin C, Foster B, Romero FA, Townley R, Casale TB. Omalizumab rapidly decreases nasal allergic response and FcepsilonRI on basophils. J Allergy Clin Immunol. 2004 Feb;113(2):297-302. doi: 10.1016/j.jaci.2003.11.044.

Hanf G, Noga O, O'Connor A, Kunkel G. Omalizumab inhibits allergen challenge-induced nasal response. Eur Respir J. 2004 Mar;23(3):414-8. doi: 10.1183/09031936.04.00024504.

Corren J, Diaz-Sanchez D, Saxon A, Deniz Y, Reimann J, Sinclair D, Davancaze T, Adelman D. Effects of omalizumab, a humanized monoclonal anti-IgE antibody, on nasal reactivity to allergen and local IgE synthesis. Ann Allergy Asthma Immunol. 2004 Sep;93(3):243-8. doi: 10.1016/S1081-1206(10)61495-0.

Pods R, Ross D, van Hulst S, Rudack C, Maune S. RANTES, eotaxin and eotaxin-2 expression and production in patients with aspirin triad. Allergy. 2003 Nov;58(11):1165-70. doi: 10.1034/j.1398-9995.2003.00276.x.

Berkman N, Ohnona S, Chung FK, Breuer R. Eotaxin-3 but not eotaxin gene expression is upregulated in asthmatics 24 hours after allergen challenge. Am J Respir Cell Mol Biol. 2001 Jun;24(6):682-7. doi: 10.1165/ajrcmb.24.6.4301.

Salib RJ, Lau LC, Howarth PH. Nasal lavage fluid concentrations of eotaxin-1 (CCL11) in naturally occurring allergic rhinitis: relationship to disease activity, nasal luminal eosinophil influx, and plasma protein exudation. Clin Exp Allergy. 2005 Aug;35(8):995-1002. doi: 10.1111/j.1365-2222.2005.02236.x.

Terada N, Hamano N, Kim WJ, Hirai K, Nakajima T, Yamada H, Kawasaki H, Yamashita T, Kishi H, Nomura T, Numata T, Yoshie O, Konno A. The kinetics of allergen-induced eotaxin level in nasal lavage fluid: its key role in eosinophil recruitment in nasal mucosa. Am J Respir Crit Care Med. 2001 Aug 15;164(4):575-9. doi: 10.1164/ajrccm.164.4.2009046.

Ong YE, Menzies-Gow A, Barkans J, Benyahia F, Ou TT, Ying S, Kay AB. Anti-IgE (omalizumab) inhibits late-phase reactions and inflammatory cells after repeat skin allergen challenge. J Allergy Clin Immunol. 2005 Sep;116(3):558-64. doi: 10.1016/j.jaci.2005.05.035.

Bousquet J, Cabrera P, Berkman N, Buhl R, Holgate S, Wenzel S, Fox H, Hedgecock S, Blogg M, Cioppa GD. The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma. Allergy. 2005 Mar;60(3):302-8. doi: 10.1111/j.1398-9995.2004.00770.x.

Humbert M, Beasley R, Ayres J, Slavin R, Hebert J, Bousquet J, Beeh KM, Ramos S, Canonica GW, Hedgecock S, Fox H, Blogg M, Surrey K. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy. 2005 Mar;60(3):309-16. doi: 10.1111/j.1398-9995.2004.00772.x.

Casale TB. Anti-immunoglobulin E (omalizumab) therapy in seasonal allergic rhinitis. Am J Respir Crit Care Med. 2001 Oct 15;164(8 Pt 2):S18-21. doi: 10.1164/ajrccm.164.supplement_1.2103023.

Adelroth E, Rak S, Haahtela T, Aasand G, Rosenhall L, Zetterstrom O, Byrne A, Champain K, Thirlwell J, Cioppa GD, Sandstrom T. Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen-induced seasonal allergic rhinitis. J Allergy Clin Immunol. 2000 Aug;106(2):253-9. doi: 10.1067/mai.2000.108310.

Chervinsky P, Casale T, Townley R, Tripathy I, Hedgecock S, Fowler-Taylor A, Shen H, Fox H. Omalizumab, an anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis. Ann Allergy Asthma Immunol. 2003 Aug;91(2):160-7. doi: 10.1016/S1081-1206(10)62171-0.

Kuehr J, Brauburger J, Zielen S, Schauer U, Kamin W, Von Berg A, Leupold W, Bergmann KC, Rolinck-Werninghaus C, Grave M, Hultsch T, Wahn U. Efficacy of combination treatment with anti-IgE plus specific immunotherapy in polysensitized children and adolescents with seasonal allergic rhinitis. J Allergy Clin Immunol. 2002 Feb;109(2):274-80. doi: 10.1067/mai.2002.121949.

Casale TB, Bernstein IL, Busse WW, LaForce CF, Tinkelman DG, Stoltz RR, Dockhorn RJ, Reimann J, Su JQ, Fick RB Jr, Adelman DC. Use of an anti-IgE humanized monoclonal antibody in ragweed-induced allergic rhinitis. J Allergy Clin Immunol. 1997 Jul;100(1):110-21. doi: 10.1016/s0091-6749(97)70202-1.

Deniz YM, Gupta N. Safety and tolerability of omalizumab (Xolair), a recombinant humanized monoclonal anti-IgE antibody. Clin Rev Allergy Immunol. 2005 Aug;29(1):31-48. doi: 10.1385/criai:29:1:031.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Paterniti M, Kelly DC, Eckman JA, Sterba PM, Hamilton RG, Bochner BS, Macglashan DW Jr, Saini SS. Cat allergen-induced blood basophil reactivity in vitro predicts acute human nasal allergen challenge responses in vivo. Clin Exp Allergy. 2011 Jul;41(7):963-9. doi: 10.1111/j.1365-2222.2011.03719.x. Epub 2011 Mar 29.

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Responsible Party:	Johns Hopkins University
ClinicalTrials.gov Identifier:	NCT00604786
Other Study ID Numbers:	NA_00007520 U19AI070345 ( U.S. NIH Grant/Contract )
First Posted:	January 30, 2008 Key Record Dates
Results First Posted:	April 4, 2017
Last Update Posted:	May 10, 2017
Last Verified:	April 2017

Keywords provided by Johns Hopkins University:


Basophils Mast Cells IgE IgE receptors omalizumab

Additional relevant MeSH terms:

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Rhinitis Rhinitis, Allergic Respiratory Tract Infections Infections Nose Diseases Respiratory Tract Diseases Otorhinolaryngologic Diseases Respiratory Hypersensitivity	Hypersensitivity, Immediate Hypersensitivity Immune System Diseases Omalizumab Anti-Allergic Agents Anti-Asthmatic Agents Respiratory System Agents

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