Clinical Trial of Omalizumab for Allergen Sensitized and Exposed Individuals With COPD

Inclusion Criteria:

• Able and willing to provide informed consent.

• Age >40 years at screening.

• Combustible tobacco cigarette exposure >10 pack-years.

• Self-report of physician diagnosis of COPD and currently on dual or triplelong-acting inhaled therapy (ICS/LABA/LAMA, ICS/LABA, LABA/LAMA).

• COPD Assessment Test (CAT) score of >15 OR history of at least one documentedmoderate (requiring treatment with oral corticosteroids) or severe (requiring EDvisit or hospitalization) COPD exacerbation in the past year.

• Participants of childbearing potential must have negative pregnancy test upon studyentry.

• Female (and male) participants with reproductive potential must agree to use FDAapproved methods of contraception for duration of study.

• Post-bronchodilator FEV1/FVC ratio < 0.7 and FEV1% predicted < 80%.

• Sensitization to one or more of five common indoor allergens including cat, dog,mouse, cockroach, dust mite defined with positive skin prick test (SPT) (SPT whealsize at least 3 mm greater than negative control). Positive specific IgE testingwithin 12 months of randomization to cat, dog, mouse, cockroach, or dust mite willbe accepted in lieu of skin prick test if SPT is not interpretable or SPT cannot besafely performed.

• Exposure to the same allergen to which individual is sensitized based on measurementin home settled dust (1 U/g cockroach, 1 μg/g mouse, 2 μg/g dust mite, (Der f 1), 8 μg/g for cat and dog).

Exclusion Criteria:

• Inability or unwillingness of a participant to give written informed consent orcomply with study protocol.

• Live in a location other than home (i.e., care facility)

• Actively breastfeeding.

• Current asthma diagnosis.

• Other lung disease (cystic fibrosis, pneumoconiosis, bronchiectasis or otherwise)that is considered the primary respiratory diagnosis and would interfere withparticipation in the study

• Reduced life expectancy due to other disease that in the opinion of the investigatormay interfere with participation in the study.

• Participants with severe medical condition(s) that in the view of the investigatorprohibits participation in the study.

• Received or listed for a lung transplant.

• Surgical or bronchoscopic lung volume reduction surgery in the 12 months prior toscreening.

• History of infection or active infection due to Mycobacterium tuberculosis

• Active parasitic infection diagnosed and/or treated within 6 months of randomization

• Currently receiving allergen immunotherapy.

• History of anaphylaxis from medications, foods or otherwise.

• Current active prescription for epinephrine autoinjector for treatment of severechronic urticaria.

• Known sensitivity to study drug(s) or another biologic medication.

• Use of any other investigational agent for COPD in the last 90 days. If the otherinvestigational agent being used is a biologic agent, this must be washed out for 6months prior to randomization.

• Active use of biologic medication (monoclonal antibody) for treatment of respiratorydisease in the past 6 months (benralizumab, omalizumab, mepolizumab, resilizumab,dupliumab, tezepelumab, or other similar medication or use of biologic medicationfor treatment of any non-respiratory disease in the past 3 months.

• Use of chronic systemic corticosteroids at doses above 10mg daily prednisone or theequivalent.

• Use of systemic corticosteroid course for acute exacerbation of COPD within 4 weeksof randomization.

• Weight < 66 or >330 lbs; and total IgE < 30 IU/mL or >700 IU/mL; or no availabledosing recommendation based on weight and total IgE level.

• No ICS in background regimen for individuals with blood eosinophil count of >300 andsystemic steroid requiring exacerbation in the past year, except in case ofcontraindication to ICS such as thrush, osteoporosis, or pneumonia in the past year.