Treatment With Omalizumab to Improve the Asthmatic Response to Rhinovirus Experimental Infection With Rhinovirus
Condition: Asthma
MeSH terms: Infections; Asthma
Intervention: omalizumab; Rhinovirus (strain 16)
Intervention description: 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.
Intervention MeSH terms: Omalizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: No
Keywords: mild asthma; young adults; rhinovirus

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must be able to understand and provide written informed consent

          -  Age 18 to 40 years of age, any gender, any racial/ethnic origin

          -  Physician-diagnosed asthma

          -  Asthma Control Test (ACT) score > 19

          -  Short-acting beta-agonist use < daily in last 4 weeks

          -  Forced expired volume at 1 second (FEV1) > 70%, or FEV1/FVC ratio > 75% for subjects
             with forced vital capacity (FVC) values between 80 and 87% predicted whose FEV1 values
             fall below 70%.

          -  Positive Methacholine challenge test (i.e. at least 20% fall in FEV1 at a Methacholine
             concentration of ≤16 mg/ml) at screening protocol before enrollment.

          -  Total serum IgE level greater than or equal to 125 IU/ml evaluated during screening
             protocol.

          -  Positive test for allergic sensitization by prick skin testing documented during
             screening protocol. to allergens associated with current allergen exposure at the time
             of the rhinovirus (RV) challenge: e.g., dust mite, Alternaria, and/or ragweed for
             subjects challenged with RV in the fall, or positive tests to tree and/or grass pollen
             allergens for those challenged with RV in the spring. In keeping with the study design
             goals of inoculating subjects during periods of allergen exposure, sensitization to
             other allergens (e.g., cat or dog) will also qualify for enrollment if subjects are
             currently exposed to these allergens at home.

        Participant must be willing to comply with study procedures and requirements.

        -

        Exclusion Criteria:

          -  Inability or unwillingness of a participant or subject's legal representative to give
             written informed consent and HIPPA authorization

          -  Positive test for serum neutralizing antibody to rhinovirus (strain-16) at screening
             within 6 weeks (i.e., subjects with a neutralizing antibody titer > 1:4 will be
             excluded).

          -  To avoid RV-16 inoculations in subjects with more restrictive lung volumes, those
             whose FVC is < 80% predicted will also be excluded.

          -  Total IgE levels measured at screening protocol that are too elevated based on a
             subjects weight, to meet the recommendations for treatment with Omalizumab.

          -  Chronic heart disease, lung diseases other than asthma, or other chronic illnesses,
             including primary and/or secondary immunodeficiency.

        Hospitalization or treatment in the ER for asthma (unless the treatment involved the use of
        a bronchodilator only) during the last three years.

          -  Subjects who have had one or more night time awakenings caused by asthma symptoms
             and/or who have needed their short acting beta-2 agonist (SABA; e.g., albuterol)
             inhaler for asthma symptoms > 4 days during the week before enrollment, or during the
             week before the virus challenge.

          -  Intubation or management in the intensive care unit for an asthma exacerbation

          -  An upper or lower respiratory tract infection within six weeks prior to enrollment

          -  Previous nasal or sinus surgery within the last 12 months.

          -  Who have a 5 pack/year history of smoking, or any smoking within the last 6 months.

          -  Female subjects who are, or who plan to become, pregnant during the study, or who are
             nursing a baby. Additionally, to be included in this study, a woman of child-bearing
             potential must have a negative urine pregnancy test at screening, during the run, and
             prior to viral inoculation and agree to use an effective method of birth control such
             as, but not limited to, birth control pills, contraceptive foam, diaphragm, intra
             uterine device (IUD), abstinence, or condoms.

          -  Subjects who have used omalizumab within 12 months prior to enrollment, or inhaled
             corticosteroids,inhaled ipratropium bromide, an inhaled long acting beta agonist,
             inhaled cromolyn or nedocromil or systemic leukotriene modifiers for their asthma on a
             daily basis within 4 weeks prior to enrollment or subjects using nasal corticosteroids
             on a daily basis within 4 weeks prior to enrollment. Subjects who are currently
             receiving beta-adrenergic blocking agents.

          -  Subjects who are currently receiving allergen immunotherapy (IT), or who have received
             allergen IT within the last 3 years.

          -  Hemoglobin <11.5 g/dL for non-African American subjects or hemoglobin < 11.0 g/dL for
             African American subjects detected during screening within 6 weeks of enrollment.

          -  Absolute neutrophil count (ANC) < 1800 cells/mm3 (or 1.8 K/uL) detected during
             screening within 6 weeks of enrollment or prior to virus inoculation.