The Effect of Omalizumab on Responses to Cat Allergen Challenge

NCT00604786 | Completed Results DMC

• 2 other identifiers: NA_00007520U19AI070345
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Allergic Rhinitis

Keywords

Basophils; Mast Cells; IgE; IgE receptors; omalizumab

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Omalizumab subcutaneous

EXPERIMENTAL

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

Placebo Subcutaneous

PLACEBO COMPARATOR

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

Interventions

omalizumab DRUG

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

Also known as: Xolair

Omalizumab subcutaneous

placebo DRUG

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

Placebo Subcutaneous

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Johns Hopkins Asthma and Allergy Center

Baltimore, Maryland, 21224, United States

Location

Related Publications (26)

• 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.

  PMID: 16790701 BACKGROUND

• 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.

  PMID: 8360482 BACKGROUND

• 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.

  PMID: 11704611 BACKGROUND

• 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.

  PMID: 9013989 BACKGROUND

• 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.

  PMID: 10228046 BACKGROUND

• 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.

  PMID: 15356552 BACKGROUND

• 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.

  PMID: 1607547 BACKGROUND

• 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.

  PMID: 15746882 BACKGROUND

• 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.

  PMID: 2582257 BACKGROUND

• 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.

  PMID: 14767445 BACKGROUND

• 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.

  PMID: 15065831 BACKGROUND

• 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.

  PMID: 15478383 BACKGROUND

• 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.

  PMID: 14616128 BACKGROUND

• 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.

  PMID: 11415932 BACKGROUND

• 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.

  PMID: 16120080 BACKGROUND

• 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.

  PMID: 11520718 BACKGROUND

• 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.

  PMID: 16159624 BACKGROUND

• 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.

  PMID: 15679714 BACKGROUND

• 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.

  PMID: 15679715 BACKGROUND

• 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.

  PMID: 11704613 BACKGROUND

• 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.

  PMID: 10932067 BACKGROUND

• 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.

  PMID: 12952110 BACKGROUND

• 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.

  PMID: 11842297 BACKGROUND

• 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.

  PMID: 9257795 BACKGROUND

• 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.

  PMID: 16222082 BACKGROUND

• 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.

  PMID: 21668817 DERIVED

MeSH Terms

Conditions

Rhinitis, Allergic

Interventions

Omalizumab

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins

Limitations and Caveats

2 subject in active group did not finish the study, small sample size

Results Point of Contact

• Title: Sarbjit S. Saini
• Organization: Johns Hopkins University

ssaini@jhmi.edu

410-550-2129

Study Officials

• Sarbjit S Saini, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2008
• First Posted: January 30, 2008
• Study Start: July 1, 2007
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: May 10, 2017
• Results First Posted: April 4, 2017

Record last verified: 2017-04

Locations

US (1)