The Effect of Omalizumab on Responses to Cat Allergen Challenge

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00604786
First received: January 4, 2008
Last updated: October 27, 2009
Last verified: October 2009
  Purpose

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 Intervention
Allergic Rhinitis
Drug: omalizumab
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Pilot Study of the Effect of Omalizumab on Basophil and Mast Responses to Intranasal Cat Allergen Challenge

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Reduction of basophil surface IgE, IgE receptor, and in vitro basophil cat allergen histamine responses [ Time Frame: 3.5 months ] [ Designated as safety issue: No ]
  • Reduction of intranasal allergen induced mediator responses such as human serum albumin, tryptase, histamine, PGD2 [ Time Frame: 3.5 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Skin test titration response to cat allergen while on omalizumab [ Time Frame: 3.5 months ] [ Designated as safety issue: No ]
  • Kinetics of the high affinity receptor loss on basophils [ Time Frame: 3.5 months ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: July 2007
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active treatment
This arm will receive treatment with omalizumab at the dose FDA-approved for the treatment of allergic asthma.
Drug: omalizumab

IgE 30-100 int. units/mL:

30-90 kg: 150 mg every 4 weeks >90-150 kg: 300 mg every 4 weeks

IgE >100-200 int. units/mL:

30-90 kg: 300 mg every 4 weeks >90-150 kg: 225 mg every 2 weeks

IgE >200-300 int. units/mL:

30-60 kg: 300 mg every 4 weeks >60-90 kg: 225 mg every 2 weeks >90-150 kg: 300 mg every 2 weeks

IgE >300-400 int. units/mL:

30-70 kg: 225 mg every 2 weeks >70-90 kg: 300 mg every 2 weeks >90 kg: Do not administer dose

IgE >400-500 int. units/mL:

30-70 kg: 300 mg every 2 weeks >70-90 kg: 375 mg every 2 weeks >90 kg: Do not administer dose

IgE >500-600 int. units/mL:

30-60 kg: 300 mg every 2 weeks >60-70 kg: 375 mg every 2 weeks >70 kg: Do not administer dose

IgE >600-700 int. units/mL:

30-60 kg: 375 mg every 2 weeks >60 kg: Do not administer dose

Other Name: Xolair
Placebo Comparator: Placebo Drug: placebo

IgE 30-100 int. units/mL:

30-90 kg: placebo every 4 weeks >90-150 kg: placebo every 4 weeks

IgE >100-200 int. units/mL:

30-90 kg: placebo every 4 weeks >90-150 kg: placebo every 2 weeks

IgE >200-300 int. units/mL:

30-60 kg: placebo every 4 weeks >60-90 kg: placebo every 2 weeks >90-150 kg: placebo every 2 weeks

IgE >300-400 int. units/mL:

30-70 kg: placebo every 2 weeks >70-90 kg: placebo every 2 weeks >90 kg: Do not administer dose

IgE >400-500 int. units/mL:

30-70 kg: placebo every 2 weeks >70-90 kg: placebo every 2 weeks >90 kg: Do not administer dose

IgE >500-600 int. units/mL:

30-60 kg: placebo every 2 weeks >60-70 kg: placebo every 2 weeks >70 kg: Do not administer dose

IgE >600-700 int. units/mL:

30-60 kg: placebo every 2 weeks >60 kg: Do not administer dose


Detailed Description:

Omalizumab is a monoclonal antibody directed against 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, 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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
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 CAP-RAST to Fel d 1 > 0.35 kU/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, cromolyns, 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 FEV1 < 80%, moderate to severe asthma classification per 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 ESR, hematocrit < 32%, WBC count 2400/microliter lower limit of normal, platelet < 75000/microliter, creatinine > 141.4 micromolar/L, or 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
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: NCT00604786

Locations
United States, Maryland
Johns Hopkins Asthma and Allergy Center
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Johns Hopkins University
Investigators
Principal Investigator: Sarbjit S Saini, M.D. Johns Hopkins University
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr. Sarbjit S. Saini, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00604786     History of Changes
Other Study ID Numbers: NA_00007520, U19AI070345
Study First Received: January 4, 2008
Last Updated: October 27, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Johns Hopkins University:
Basophils
Mast Cells
IgE
IgE receptors
omalizumab

Additional relevant MeSH terms:
Omalizumab
Anti-Allergic Agents
Anti-Asthmatic Agents
Pharmacologic Actions
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014