This research is being done to test if a drug called omalizumab can help people with Chronic Obstructive Pulmonary Disease (COPD) and allergies.

Each participant will be in the study for about 16 months, including 1-3 months of screening, 12 months of receiving the study drug at a clinic, and a follow-up call one month after your final clinic visit.

This study is for people 40 years and older with COPD who also have allergens in their home that they are allergic to, like pet dander, cockroaches or dust mites.

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 triple long-acting inhaled therapy (ICS/LABA/LAMA, ICS/LABA, LABA/LAMA).
• COPD Assessment Test (CAT) score of >15 OR history of at least one documented moderate (requiring treatment with oral corticosteroids) or severe (requiring ED visit or hospitalization) COPD exacerbation in the past year.
• Participants of childbearing potential must have negative pregnancy test upon study entry.
• Female (and male) participants with reproductive potential must agree to use FDA approved 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 wheal size at least 3 mm greater than negative control). Positive specific IgE testing within 12 months of randomization to cat, dog, mouse, cockroach, or dust mite will be accepted in lieu of skin prick test if SPT is not interpretable or SPT cannot be safely performed.
• Exposure to the same allergen to which individual is sensitized based on measurement in 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 or comply 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 with participation in the study
• Reduced life expectancy due to other disease that in the opinion of the investigator may interfere with participation in the study.
• Participants with severe medical condition(s) that in the view of the investigator prohibits participation in the study.
• Received or listed for a lung transplant.
• Surgical or bronchoscopic lung volume reduction surgery in the 12 months prior to screening.
• 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 severe chronic 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 other investigational agent being used is a biologic agent, this must be washed out for 6 months prior to randomization.
• Active use of biologic medication (monoclonal antibody) for treatment of respiratory disease in the past 6 months (benralizumab, omalizumab, mepolizumab, resilizumab, dupliumab, tezepelumab, or other similar medication or use of biologic medication for treatment of any non-respiratory disease in the past 3 months.
• Use of chronic systemic corticosteroids at doses above 10mg daily prednisone or the equivalent.
• Use of systemic corticosteroid course for acute exacerbation of COPD within 4 weeks of randomization.
• Weight < 66 or >330 lbs; and total IgE < 30 IU/mL or >700 IU/mL; or no available dosing recommendation based on weight and total IgE level.
• No ICS in background regimen for individuals with blood eosinophil count of >300 and systemic steroid requiring exacerbation in the past year, except in case of contraindication to ICS such as thrush, osteoporosis, or pneumonia in the past year.

The participant and the study team (e.g., PI, study physician, coordinator), with the exception of an unblinded individual, will remain masked during the study.