The MAB Trial: A Study of Tozorakimab to Reduce Lung Inflammation and Promote Lung Healing in People with COPD.

Prior treatment

• Significant concomitant respiratory diseases, such as cystic fibrosis, and pulmonary fibrosis.
• Recent acute exacerbation event requiring oral corticosteroids or antibiotics (any dose for more than 3 days) or respiratory tract infection within 4 weeks prior to screening.
• Malignancy, current or within the past 5 years, except for adequately treated non-invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma-in-situ treated with apparent success more than one year prior to enrolment. Suspected malignancy or undefined neoplasms.

Other illness

• Any unstable disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric disorder, major physical and/or cognitive impairment that, in the opinion of the Investigator, could: a. Affect the safety of the participant throughout the study b. Influence the findings of the study or their interpretation c. Impede the participant’s ability to complete the entire duration of the study and/or comply with the study visit schedule and procedures.
• History of any known primary immunodeficiency disorder excluding asymptomatic selective immunoglobulin A or IgG subclass deficiency.
• Diagnosis of HIV as determined by medical history.
• Hepatitis: Medical history of or treatment for hepatitis B or hepatitis C, except for cured hepatitis C. a. Positive test for HBsAg b. Positive test for anti-HBc: Participants who test positive for anti-HBc antibody but negative for HBsAg may be enrolled if their HBV DNA test result is negative c. Positive test for anti-hepatitis C antibody: Participants who test positive for anti-hepatitis C antibody may be enrolled if their hepatitis C virus RNA test result is negative in the absence of cirrhosis
• Long-term oxygen therapy or NIPPV for type 2 respiratory failure. Participants using continuous positive airway pressure for sleep apnoea syndrome are permitted in the study.

Lab values

• Any significant abnormal laboratory results at screening, which, in the opinion of the investigator, may put the subject at risk if taking take part in the study.
• Neutropenia (neutrophils < 2,0*109/L)

Other

• Current diagnosis of Asthma.

• Willing and able to consent to participate in the trial.
• CAAT ≥10 and cough and sputum domain ≥2 at Visit 1.
• Women of childbearing potential (WOCBP) and males must be willing to use a highly effective method of contraception (hormonal or barrier method of birth control; abstinence).
• Age ≥ 40 <85 years old.
• Male or female.
• Able to understand written and spoken English (UK participants) or country’s official language (non-UK participants).
• Clinically diagnosed chronic obstructive airway disease at least 1-year prior screening.
• FEV1/FVC<0.7 and FEV1 ≥ 30% predicted value (and ≥ 1.0L) at Visit 1.
• Current or ex-smokers with ≥ 10 pack years past smoking history (25-40% of participants will be current smokers) a. Former smokers will be defined as participants who are currently not smoking and with smoking cessation ≥ 6 months before screening with an intention to quit permanently. b. Current smokers will be defined as participants who are currently smoking tobacco (at least one cigarette per day on average during the past 7 days) and are not presently participating in smoking cessation. c. Electronic cigarettes (e-cigarettes referring to devices that vaporise liquids [e.g., nicotine, THC]) and heated tobacco product use do not contribute to the pack-year count for eligibility. E-cigarette smoking/heated tobacco smoking status being irrelevant to categorisation/randomisation.
• On stable treatment for at least 3 months prior to screening with COPD inhaled maintenance dual or triple therapy (LABA/LAMA, ICS/LABA, ICS/LAMA, ICS/LABA/LAMA). During this period: a. Individual component changes or switches between devices are allowed if the participant remains on the same class therapies in equivalent doses b. Short-term changes in background treatment regimen during COPD exacerbation are acceptable. c. Short-acting muscarinic antagonists taken at regular scheduled intervals (at a minimum frequency of 3 times daily) will be considered equivalent to LAMA. d. If the participant is being treated with oral COPD maintenance therapy (macrolides, roflumilast), these treatments must also be stable for at least 3 months before enrolment.
• History of ≥1 moderate to severe exacerbation event treated with systemic corticosteroid and/or antibiotic in the 12 months prior to screening.