A Phase IIb Randomized Study to Evaluate the Efficacy and Safety of AZD0292 in Patients with Bronchiectasis and Chronic Pseudomonas aeruginosa Colonization

The primary objective of this study is to evaluate the efficacy of intravenous AZD0292 compared to a placebo in reducing the rate of moderate-to-severe pulmonary exacerbations in participants with bronchiectasis and chronic Pseudomonas aeruginosa colonization. 5

Secondary objectives include:

• Evaluation of the effect of AZD0292 on severe exacerbations.
• Assessment of quality of life using the QoL-B Respiratory Symptom Scale Score (QoL-B-RSS) and the SGRQ respiratory domain.
• Determination of the time to the first pulmonary exacerbation.
• Evaluation of the pharmacokinetics of intravenous doses.
• Assessment of immunogenicity.
• Evaluation of safety.

This clinical trial involves 323 participants diagnosed with non-cystic fibrosis bronchiectasis and chronic Pseudomonas aeruginosa colonization. The study population includes both male and female patients, including vulnerable populations, within specified age categories. Eligible individuals must be at least 18 years of age and weigh 35 kg or more. Diagnosis of the condition requires physician confirmation and computed tomography evidence of abnormal bronchial dilation in at least one lobe. Participants must be receiving standard of care therapy and have a documented history of at least two moderate or one severe pulmonary exacerbation requiring antibiotics within the previous 12 months. Clinical stability is required, defined as being free from exacerbations for four weeks prior to randomization. Additional requirements include a forced expiratory volume in one second of at least 25% of the predicted value. Documentation of colonization via polymerase chain reaction or culture within the last 24 months is necessary, with positive sputum cultures required within five weeks of randomization.

This Phase IIb, randomized, double-blind, placebo-controlled, parallel, multidose study is designed to evaluate the efficacy, safety, and pharmacokinetics of AZD0292 in individuals aged 12 years and older with bronchiectasis and chronic Pseudomonas aeruginosa colonization. The primary objective is to assess the effect of intravenous AZD0292 compared to a placebo on the annualized rate of moderate-to-severe pulmonary exacerbations. The research methodology involves a comparison between the test substance and a placebo to determine changes in clinical outcomes and safety profiles. Secondary endpoints include the annualized rate of severe exacerbations, changes in quality of life scores, time to first exacerbation, and the incidence of immunogenicity. Study procedures begin with a screening visit to confirm eligibility through clinical assessment, computed tomography, and microbiological testing. Following randomization, participants will undergo follow-up assessments to monitor disease progression and safety. The study includes monitoring for adverse events from the first dose through 12 weeks after the last administration of the investigational medicinal product. The overall trial is expected to conclude by June 2028.

The experimental treatment consists of AZD0292, which is prepared as a solution for infusion. This medication is administered via intravenous route.

The control group receives a placebo formulated for AZD0292 administration.

The efficacy of AZD0292 in participants with bronchiectasis and chronic Pseudomonas aeruginosa colonization is evaluated using several endpoints. The primary endpoint is the annualized rate of exacerbations over a variable follow-up time. Secondary efficacy assessments include the annualized rate of severe exacerbations, the time to first moderate or severe exacerbation, and the time to first severe exacerbation.

Changes from baseline in health-related quality of life are measured using the QoL-B-RSS and the SGRQ score. Additionally, serum PK concentrations of AZD0292 and the incidence of ADA to AZD0292, including ADA titers, are assessed at all collected timepoints.