Treatment With Omalizumab to Improve the Asthmatic Response to Rhinovirus Experimental Infection With Rhinovirus
Condition: Asthma
MeSH terms: Infections; Asthma
Study type: Interventional
Phase: Phase 2

Summary: 
      Population surveys have shown a positive correlation between increased levels of total serum
      immunoglobulin E (IgE) and bronchial hyperreactivity. However, it is also clear that
      exacerbations of asthma are frequently triggered by viral respiratory tract infections,
      especially those caused by human rhinovirus (RV), also known as the "common cold" virus. This
      protocol explores the relationship between rhinovirus and allergen/IgE provoked inflammation.
      Experimental challenges with human (RV) result in more persistent upper respiratory tract
      symptom scores in asthmatics than in controls. Asthmatics with high levels of IgE also show
      greater sensitivity to methacholine and higher levels of expired nitric oxide (eNO) than
      those with low levels of IgE. These data suggest that patients with asthma and high levels of
      IgE are more likely to have pre-existing inflammation of the airways before virus challenge.
      This study is being done to determine whether anti-IgE therapy (with omalizumab) will lead to
      a significant decline in inflammatory biomarkers prior to virus inoculation, and thus reduce
      the severity of clinical manifestations after an experimental human RV challenge.
    

Detailed description: 
      The study is a randomized, double-blind placebo controlled study involving a group of 42 mild
      asthmatics. Subjects will be randomized 1:1 to omalizumab (a humanized monoclonal anti-IgE
      antibody) or placebo for 8 weeks and then inoculated with rhinovirus (strain-16 produced
      under GMP conditions and approved for this research by the FDA). Clinical and laboratory
      (mechanistic) data will be evaluated for 8 weeks before and for 4 weeks after the virus
      challenge.

      The study is being done to test the hypothesis that the reduction of total free IgE in
      asthmatics treated with omalizumab for 8 weeks prior to and during an experimental RV
      challenge will lead to a significant decline in lower respiratory tract (chest) symptoms
      recorded by subjects during the first four days of infection following the challenge compared
      to lower respiratory tract symptoms recorded during the same period by asthmatic subjects who
      are treated with placebo.

      The primary endpoint will be based on the comparison of cumulative lower respiratory tract
      symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those
      treated with placebo over the first 4 days of acute infection. Diary cards will be scored
      daily for cough, shortness of breath, chest discomfort and wheezing using a modification of
      the Jackson criteria. To participate in this study, subjects must live within 90 minutes by
      car from the University of Virginia.

      Note: This protocol has been reviewed and is being monitored for safety by the NIH/NIAID
      Safety Monitoring Committee and by he IRB at the University of Virginia (IRB-HSR# 14427).
    

Intervention name(s): omalizumab; Rhinovirus (strain 16)
Intervention type(s): Drug; Biological
Intervention description(s): This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510); This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA.
Other intervention name(s): Xolair
Intervention MeSH terms: Omalizumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: mild asthma; young adults; rhinovirus