AZD0292 for bronchiectasis with long-term Pseudomonas aeruginosa lung infection

Who can take part

• Participant must be ≥ 18 years of age at the time of signing the informed consent
• Weight ≥ 35 kg
• Bronchiectasis diagnosed by a physician and confirmed by CT demonstrating abnormal bronchial dilation in ≥ 1 lobe. Note: A historical CT scan within the past 5 years is acceptable. If not available, a CT scan should be conducted at screening to confirm eligibility
• Participants who are receiving appropriate standard of care therapy per local guidelines and have a documented history of ≥ 2 moderate exacerbations or ≥ 1 severe exacerbation in the preceding 12 months requiring antibiotics
• Participants who are clinically stable and free from an exacerbation of bronchiectasis for 4 weeks prior to randomization
• Participants with pre- or post-bronchodilator FEV1 ≥ 25% predicted value at screening
• Presence of positive (PCR or culture) PsA in an airway sample at least once in the last 24 months prior to screening
• Presence of culture positive PsA in sputum at least within 5 weeks of randomization a) Participants who have previously received PsA eradication therapy, as determined appropriate by their treating provider, but remain colonized with PsA are eligible for the study
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol

Who cannot take part

• Receipt of investigational products indicated for the treatment or prevention of bronchiectasis exacerbations or expected receipt during the study
• Participants with CF on CFTR modulator therapies which are newly initiated within the previous 3 months prior to screening
• Female participants who are pregnant, lactating, or of childbearing potential and not using a highly effective method of contraception or abstinence from at least 4 weeks prior to study intervention administration and until at least 6 months after study intervention administration
• Evidence of active tuberculosis or active nontuberculous mycobacteria being treated or requiring treatment. Active tuberculosis may be suspected if a participant has a cough for more than 2 weeks with concurrent fever, night sweats, weight loss, or hemoptysis. Investigation for active or latent TB, with interferon gamma release assay (IGRA) and/or chest X-ray, should be considered if deemed clinically indicated by the Investigator. Participants currently receiving treatment for active TB or nontuberculous mycobacteria may be considered after completion of an appropriate course of therapy
• Malignancy, current or within the previous 5 years, except for stable prostate cancer, 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
• Treatment with long term anti-PsA antibiotics, macrolides, or DPP-1 inhibitors, which are newly initiated within the 3 months prior to screening
• Chronic immunosuppressive therapy (including prednisolone > 5 mg or equivalent) newly initiated within the last 3 months
• Evidence of an active allergic bronchopulmonary aspergillosis being treated or requiring treatment
• History of severe adverse reaction associated with a mAb, and/or history of severe allergic reaction (eg, anaphylaxis that required the use of epinephrine/adrenaline or hospitalization), and/or history of immune complex disease (Type III hypersensitivity reactions) to monoclonal antibody administration
• AIDS or Advanced human immunodeficiency virus disease (CD4 count of < 200 cells/mm3)
• Primary lung diagnosis other than bronchiectasis
• Need for long term supplemental oxygen. Oxygen use for ambulation and relief of breathlessness after exercise is allowed