Study to Evaluate the Effect of Omalizumab on Improving the Tolerability of Specific Immunotherapy in Patients With Persistent Allergic Asthma
Condition: Allergic Asthma
MeSH terms: Asthma
Intervention: Placebo; Omalizumab; Immunotherapy; Immunotherapy
Intervention description: Doses of placebo were administered subcutaneously every 2 to 4 weeks according to the US product label, depending on the patient's body weight and baseline serum IgE.; Doses of omalizumab were administered subcutaneously every 2 to 4 weeks according to the US product label, depending on the patient's body weight and baseline serum IgE.; Customized allergen extracts were prepared centrally for each patient based on his/her specific skin test results. Four vials containing dilutions of the patient's extract were provided. Investigators initiated dosing according to the protocol for the cluster dosing titration regimen, beginning with vial #4 (the most dilute) and progressing to vial #1, which was the most concentrated or "maintenance" solution. Each dose was administered subcutaneously into the deltoid region as a single injection. During study visits that required multiple IT injections, each injection was to be given at least 30 minutes apart. During weeks that required multiple visits for IT injections, each visit was to be separated by at least 48 hours.; Customized allergen extracts were prepared centrally for each patient based on his/her specific skin test results. Four vials containing dilutions of the patient's extract were provided. Investigators initiated dosing according to the protocol for the cluster dosing titration regimen, beginning with vial #4 (the most dilute) and progressing to vial #1, which was the most concentrated or "maintenance" solution. Each dose was administered subcutaneously into the deltoid region as a single injection. During study visits that required multiple IT injections, each injection was to be given at least 30 minutes apart. During weeks that required multiple visits for IT injections, each visit was to be separated by at least 48 hours.
Intervention MeSH terms: Omalizumab; Immunomodulating Agents; Immunologic Factors
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 275.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Allergic Asthma, IgE, immunotherapy, omalizumab

Summary:

      This study is designed to investigate the use of omalizumab as a pretreatment for patients
      with persistent allergic asthma who are candidates for allergen immunotherapy (ie, allergy
      shots) and will test the hypothesis that omalizumab may reduce the rate of systemic reactions
      to immunotherapy in patients with persistent allergic asthma.
    

Eligibility criteria:

        Inclusion Criteria:

        Patients were eligible for inclusion if they met all of the following criteria:

        Informed Consent

          -  Patients who were informed of the study procedures and medications and provided their
             written informed consent

        Demographics

          -  Male or female

          -  Any race

          -  Ages 18 - 55 years

          -  Body weight >=20 kg and <=150 kg

          -  Total serum IgE concentration >=30 and <=700 IU/mL at Visit 0

        Disease Definitions/Medications

          -  History of at least moderate persistent allergic asthma (consistent with Global
             Initiative for Asthma [GINA] guidelines of >=1 year in duration

          -  On a stable asthma treatment regimen including inhaled corticosteroids for the
             preceding 4 weeks

          -  An FEV1 while withholding short-acting beta-agonists for at least 6 hours and
             long-acting beta-agonists for at least 12 hours, of >=75% of the predicted value at
             Visit 0

          -  Evidence of reversible airway obstruction, as defined by an increase in FEV1 of >=12%
             between 20 to 30 minutes after 4 puffs (or less at the discretion of the investigator)
             of inhaled short-acting beta-agonist administration at Visit 0 or within the preceding
             year

          -  Documented sensitivity to perennial aeroallergens, as evidenced by a positive skin
             test (wheal >=5mm greater than saline control) to at least 1 of 3 perennial
             aeroallergens (house dust mite, cat, or dog) at Visit 0 or within the preceding year

          -  Average PEFR variability <=20% (calculated as [(PM PEF - AM PEF)/(PM PEF + AM PEF)/2 x
             100) during the 2-week screening period

          -  Pre-specified level of nocturnal asthma symptoms (i.e., a mean nocturnal asthma score
             of >0 and <=0.5) and a mean combined clinical symptom score (nocturnal, morning, and
             daytime) of >0 and <=3 during the screening period

          -  Non-smoker for at least 1 year prior to Visit 1, with a smoking history of no more
             than 10 pack-years (i.e., 1 pack [20 cigarettes] per day for 10 years)

          -  Judged to be in good physical and mental health (except for his/her asthma), based on
             medical history, physical examination, and routine laboratory data, and appeared to be
             able to successfully complete this trial

        Exclusion Criteria:

        Patients were to be excluded from participation if they met any of the following criteria:

        Pulmonary

          -  History of intubation for asthma

          -  Asthma exacerbation requiring treatment with systemic steroids within the preceding 3
             months

          -  Asthma exacerbation requiring treatment in an emergency department or a hospital
             admission in the preceding 6 months

          -  Upper respiratory tract infection or sinusitis within the preceding 4 weeks

          -  History of an anaphylactic allergic reaction (except to stinging insects, foods, or
             drugs other than omalizumab)

          -  History of treatment with immunotherapy to any allergen within past 3 years

          -  History of aspirin or non steroidal anti-inflammatory drug (NSAID)-related asthma;
             patients could have been included in NSAIDs use was avoided for the duration of the
             study

        General Medical

          -  History of or current malignancy

          -  Any clinically significant uncontrolled systemic disease or a history of such disease
             (e.g., infectious, hematologic, renal, hepatic, endocrinologic, gastrointestinal, or
             cardiovascular disease) within the previous 3 months

          -  Clinically significant laboratory abnormalities at Visit 1

          -  Platelet levels <=130 x 10 9/L at visit 1

          -  Women of childbearing potential who were not practicing a medically approved
             contraception method (e.g., oral, subcutaneous, mechanical, or surgical
             contraception), as well as women who were pregnant or nursing

          -  History of hypersensitivity to any ingredients, including excipients (sucrose,
             histidine, or polysorbate 20) of the study medication or drugs related to omalizumab
             (e.g., monoclonal anti-bodies or polyclonal gammaglobulin)

          -  Severe medical condition(s) that, in the view of the investigator, prohibited
             participation in the study

          -  Previous treatment with omalizumab within 1 year of screening

          -  Considered by the investigator to be potentially unreliable or who may not have
             reliably attended study visits

          -  History of drug or alcohol abuse

        Procedural

          -  Unable to perform acceptable, reproducible spirometry, or PEFR measurements

          -  Unable or unwilling to comply with the study procedures as determined during the
             screening phase, including adequate completion of the diary

        Medications

        Patient took the following medications before Visit 0. These medications were not permitted
        during the trial unless otherwise specified:

          -  Oral, intravenous, intramuscular, or intra-articular corticosteroids within 4 weeks

          -  Beta-adrenergic antagonists (including ocular preparations) within 1 week

          -  Antihistamines within 1 week; after skin testing was completed (Visit 0),
             antihistamines could be used as needed for the remainder of the study

          -  Intravenous gammaglobulin or immunosuppressants within 4 weeks

          -  Tricyclic antidepressants within 1 week

          -  Investigational drugs within 4 weeks