The Effect of Omalizumab on Responses to Cat Allergen Challenge

Allergic Rhinitis Clinical Trial

Official title:

Pilot Study of the Effect of Omalizumab on Basophil and Mast Responses to Intranasal Cat Allergen Challenge

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00604786
• Other study ID #: NA_00007520
• Secondary ID: U19AI070345
• Status: Completed
• Phase: N/A
• First received: January 4, 2008
• Last updated: March 30, 2017
• Start date: July 2007
• Est. completion date: January 2009

Study information

• Verified date: March 2017
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Allergic Rhinitis
• Rhinitis
• Rhinitis, Allergic

Intervention

Drug:
• omalizumab
Dosing is based on IgE level and weight given every 2 or 4 weeks
• placebo
Dosing is based on IgE level and weight given every 2 or 4 weeks

Locations

Country	Name	City	State
United States	Johns Hopkins Asthma and Allergy Center	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (25)

Adelroth E, Rak S, Haahtela T, Aasand G, Rosenhall L, Zetterstrom O, Byrne A, Champain K, Thirlwell J, Cioppa GD, Sandström 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. — View Citation

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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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

Humbert M, Beasley R, Ayres J, Slavin R, Hébert 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. — View Citation

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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. — View Citation

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. — View Citation

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. — View Citation

Nathan RA, Eccles R, Howarth PH, Steinsvåg 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. Review. — View Citation

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. — View Citation

Pods R, Ross D, van Hülst 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

Strunk RC, Bloomberg GR. Omalizumab for asthma. N Engl J Med. 2006 Jun 22;354(25):2689-95. Review. — View Citation

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. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Basophil Surface IgE	Flow cytometry in mean fluorescence units.; 100%*[(3.5 month value minus baseline value)/baseline value]	Change from baseline to 3.5 months

External Links

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