Clinical Trials

Inclusion Criteria:

• Signed Informed Consent Form.
• Age 18-65 years at time of signing Informed Consent Form.
• Body mass index (BMI) of 18-35 kg/m^2.
• Physician-diagnosed asthma for at least 12 months prior to screening.
• Documented history of positive skin test or in vitro reactivity to a perennial aeroallergen.
  • If no historical documentation is available, the skin test or in vitro reactivity to a perennial aeroallergen will need to be performed during screening.
• Eligibility per the study drug-dosing table (serum IgE level ≥ 30 to ≤ 700 IU/mL and body weight ≥ 30 to ≤ 150 kg) and ability to be dosed per the USPI dosing table.
• Able to comply with asthma control medication adherence, physical activity and sleep monitoring data collection, and eDiary requirements during screening period. Compliance will be assessed during the last 2 weeks prior to study enrollment and non-compliance is defined as:
  • Asthma control medication use < 70% of the time during the 2 week period before study enrollment;
  • Wearing the physical activity and sleep monitor less than approximately 80% of the time (approximately 90 hours during the day and approximately 44 hours at night) for each week during the 2 week period before study enrollment);
  • Using the eDiary < 5 out of 7 days for each week during the 2 week period before study enrollment.
• Able to safely complete incremental exercise tolerance at screening.
• Able to comply with the study protocol for the duration of the study, in the investigator's judgment, including but not limited to:
  • Able and willing to use a wrist-worn physical activity and sleep monitor every day and night for the duration of the study;
  • Able and willing to use eDiary device throughout the duration of the study.
• Pre-bronchodilator FEV1 of 40%-80% of predicted at screening..
• Documented history of variable airflow obstruction or hyper-responsiveness within 12 months of study entry via at least one of the following criteria:
  • FEV1 bronchodilator response ≥ 12% and ≥ 200 mL with up to 400 mg albuterol;
  • Concentration of methacholine needed to produce a 20% decrease in FEV1 from baseline (PC20 ≤ 8 mg/mL or PD20 ≤ 200 mg);
  • In patients with a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) < 70%, FEV1 variability should be ≥ 12% spontaneously (e.g., between clinic visits) or in response to oral corticosteroids.
  • If no documented history is available, an assessment will need to be performed during screening.
• On inhaled corticosteroid (ICS) therapy at a total daily dose ≥ 500 mg of fluticasone propionate or equivalent and at least one second controller (long-acting beta agonist [LABA], long-acting muscarinic antagonist [LAMA], leukotriene receptor antagonist [LTRA]) for ≥ 3 months prior to screening, with no changes within 4 weeks prior to screening or during the screening period and no anticipated changes in controller dosing regimens throughout the study.
• Uncontrolled asthma during the screening period, defined as an Asthma Control Questionnaire 5 (ACQ5) ≥ 0.75 score and both of the following symptoms that are not controlled according to EPR (2007) and GINA (2019).
  • Night time awakening due to asthma in the past 4 weeks;
  • Activity limitations due to asthma in the past 4 weeks.
• Sleep disturbance due to asthma (e.g., cough, wheezing, etc.) in the opinion of the investigator.
• Medical Research Council Dyspnoea scale ≥ 2 at screening.
• Impaired exercise capacity defined as VO2 max % of predicted ≤ 80% of healthy volunteers (Koch et al. 2009) during the incremental exercise test at screening.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or to use adequate contraception during the treatment period and for 60 days after the final dose of study drug.
• A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.
• The following are examples of adequate contraceptive methods: bilateral tubal ligation; male sterilization; hormonal contraceptives; hormone-releasing intrauterine devices; copper intrauterine devices; male or female condom with spermicide; and cap, diaphragm, or sponge with spermicide.
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.  If required per local guidelines or regulations, locally recognized acceptable methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.

Exclusion Criteria:

• Known history of anaphylaxis/hypersensitivity to omalizumab.
• Treatment with investigational drugs within 12 weeks or 5 half-lives (whichever is longer) prior to screening.
• Treatment with monoclonal antibodies (e.g., omalizumab, mepolizumab, dupilumab) for 6 months prior to screening.
• Treatment with non-steroid immunosuppressants (e.g., cyclosporine, methotrexate, azathioprine, mycophenolate, sirolimus, tacrolimus) within 2 months or 5 half-lives, whichever is longer, prior to screening.
• Asthma exacerbation, defined as new or increased asthma symptoms that require use of systemic corticosteroids for ≥ 3 days and/or hospitalization or emergency visit with systemic corticosteroid administration within 4 weeks prior to screening.
• Intubation for respiratory failure due to asthma within 12 months prior to screening.
• Maintenance oral corticosteroid therapy, defined as daily or alternate-day oral corticosteroid within 3 months prior to screening or during the screening period.
• Treatment with systemic (oral, IV, or IM) corticosteroids within 4 weeks prior to screening or during the screening period for any reason, including an acute exacerbation event.
• Inability to withhold short acting bronchodilators for a period up to 6 hours.
• Isolated diagnosis of exercise induced asthma without chronic symptoms.
• History of interstitial lung disease, COPD, or other clinically significant lung disease other than asthma.
• Current participation or participation in the last 6 months in pulmonary rehabilitation prior to screening.
• Current malignancy or history of malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix or non-melanoma skin carcinoma that has been treated or excised and is considered resolve.
• Any serious medical condition (including but not limited to significant arrhythmia, uncontrolled hypertension) or abnormality in clinical laboratory tests that precludes the patient’s safe participation in and completion of the study in the opinion of the investigator.
• Elevated IgE due to hyperimmunoglobulin E syndrome or allergic bronchopulmonary aspergillosis.
• Unable to complete cardiopulmonary exercise testing and/or perform physical activity due to underlying cardiac, neurologic or orthopedic conditions.
• Ongoing physician-treated sleep disorder that is unrelated to asthma within 6 months prior to screening.
• Use of any prescription or over-the-counter sedative sleep medication for the duration of the study (e.g., zolpidem)
• Physician determination of patient lifestyle that can interfere with study endpoints, (e.g., rotating shifts, any prescription or over the counter medical cannabis, use of recreational drugs, etc.).
• Planned major surgery during the course of the study.
• Current smoker or past smoker with > 10 pack years
• Known HIV infection at screening.
• Known acute or chronic infections with hepatitis C virus (HCV) and hepatitis B virus (HBV) at screening
• Infection that meets any of the following criteria:
  • Resulted in hospital admission within 4 weeks prior to screening;
  • Required treatment with intravenous or intramuscular antibiotics within 4 weeks prior to screening;
  • Any active infection that required treatment with oral antibiotics within 2 weeks prior to screening.
    • Note: Antibiotics are considered to include any antimicrobial therapy used to treat bacterial, fungal, parasitic, viral, or other infections.
• Active parasitic infection, including nematodes (e.g., Ascaris, Ancylostoma), platyhelminths (e.g., Schistosoma), or Listeria monocytogenes infection within 6 months prior to screening.
• Active tuberculosis requiring treatment within 12 months prior to screening:
  • Patients who have completed treatment for tuberculosis at least 12 months prior to screening and have no evidence of recurrent disease are permitted.
• Initiation of or change in allergen immunotherapy within 3 months prior to screening.
• Initiation of or change in aspirin desensitization within 4 months prior to screening.
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 60 days after the last dose of omalizumab:
• Women of childbearing potential must have a negative serum pregnancy test result during the screening period.
• History of alcohol, drug, or chemical abuse within 6 months of screening.