Phase 1/Phase 2a Study of AERO-007 Inhalation Solution, a Nebulized LABA/LAMA Combination for Maintenance Treatment of COPD

Prior treatment

• Lower respiratory tract infection within 6 weeks prior to the Screening Visit
• Major surgery (requiring general anaesthesia) within 6 weeks prior to the Screening Visit
• Current or previous use of tobacco, nicotine products or e-cigarettes within 6 months
• Positive urine drugs of abuse test and/or alcohol breath test
• Participation in another investigational drug study within 30 days, 5 half-lives or twice the duration of the biological effect
  • Cohort 2 (Subjects with COPD)
• Prior lung volume reduction surgery or history of chest/lung irradiation
• Daily oxygen therapy for \> 12 hours per day
• Current or recent history (previous 12 months) of excessive use or abuse of alcohol (males \>21 units per week and females \>14 units per week)
• Current evidence or history (within the past 2 years) of abusing legal drugs or use of illegal drugs or substances
• Major surgery (requiring general anaesthesia) within 6 weeks
• Participation in another investigational drug study within 30 days, 5 half-lives or twice the duration of the biological effect, whichever is longer

Other illness

• History of malignancy of any organ system, except for localized skin cancers, within 5 years prior to the Screening Visit
• Chronic viral infection or immunodeficiency condition
• History of any drug and/or alcohol abuse in the past 2 years
• Smoking history of \> 5 pack years
• Known hypersensitivity to any ingredients in the formulation for AERO-001, AERO-002, and AERO-007
• Current evidence or recent history of significant comorbidities; including cardiovascular disease (such as myocardial infarction, cardiac failure, uncontrolled hypertension, or life-threatening arrhythmias), uncontrolled diabetes, neurologic, psychiatric, hepatic, renal, immunological, or haematological conditions within the last 6 months
• Lower respiratory tract infection within 6 weeks
• Recent history of hospitalization due to an exacerbation of airway disease or acute worsening of COPD requiring antibiotic or corticosteroid treatment within 6 months
• Other respiratory disorders: Current diagnosis of predominant asthma, lung cancer, bronchiectasis, interstitial lung disease, tuberculosis, pulmonary hypertension, or other non-specific pulmonary diseases
• Current or recent history of medical conditions that are contraindicated for use of an inhaled LAMA (such as urinary retention or bladder neck obstruction type symptoms, prostatic hypertrophy, or narrow-angle glaucoma) within the last 6 months
• History of malignancy of any organ system, except for localized skin cancers, within 5 years
• Known hypersensitivity to any ingredients in the formulation for AERO-001, AERO-002, and AERO-007

Lab values

• Any condition or abnormality (including medical history, clinical laboratory, ECG, physical examination, or vital sign abnormalities), current or past, that, in the opinion of the Investigator
• Positive serum hepatitis B surface antigen (HbsAg), hepatitis C virus antibodies (HCV Ab) or human immunodeficiency virus (HIV) 1 and/or 2 antibodies
• Positive serum HbsAg, HCV Ab or HIV 1 and/or 2 antibodies

Other

• Regular alcohol consumption in males \>21 units per week and females \>14 units per week
• Donation of 450 mL of blood within 8 weeks
• Female subjects who are pregnant, breast-feeding or lactating
• Body mass index \>35 kg/m2
• Donation of 450 mL of blood within 8 weeks

• Male or female aged 18 to 55 years
• FEV1 \> 80% of predicted normal (using the Global Lung Function Initiative GLI 2012 reference values)
• Body mass index \> 18 and \< 32 kg/m2
• Female subjects of childbearing potential must not be pregnant, breast feeding or lactating and use, with their partner, a male condom plus an approved method of highly effective birth control method
• Female subjects of childbearing potential must have a negative serum or urine pregnancy test at the Screening Visit
• Male subjects who are sexually active with a partner of childbearing potential must use, with their partner, a male condom plus an approved method of highly effective contraception from the time of informed consent
• Participants must be in good health as determined by medical history, physical examination, vital signs, 12-lead ECG and clinical laboratory assessments at the time of screening, as judged by the Investigator
• Willing and able to provide written informed consent
• Male or female aged 40 to 75 years
• Clinical diagnosis of COPD according to the Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] Report, 2024 for at least 12 months
• Post-bronchodilator spirometry (within 30 minutes following 4 puffs of salbutamol) demonstrating the following:
• FEV1 \> 40 and \< 80% of predicted normal (using the Global Lung Function Initiative GLI 2012 reference values)
• FEV1/FVC ratio \< 0.70
• ≥ 150 mL increase from pre-bronchodilator FEV1
• Ability to change current COPD therapy and discontinue long-acting bronchodilators for the duration of the study and short-acting bronchodilators for 8 hours prior to dosing at each treatment visit
• Current or former-smokers with at least 10 pack-year smoking history (eg, at least 1 pack/day for 10 years, 10 packs/day for 1 year)
• Ability to perform reproducible spirometry according to the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines
• Female subjects of childbearing potential must not be pregnant, breast feeding or lactating and use, with their partner, a male condom plus an approved method of highly effective birth control method
• Willing and able to provide written informed consent

Criteria the registry did not label

• Cohort 1 (Healthy Subjects)