A phase 2 trial of Gremubamab compared to placebo in participants with bronchiectasis and chronic Pseudomonas aeruginosa infection

The primary objective of this phase 2 trial is to evaluate the efficacy of **Gremubamab** on the **Pseudomonas aeruginosa** bacterial burden in sputum at week 12 in participants with **bronchiectasis** and chronic **Pseudomonas aeruginosa** infection. This is clinically relevant as reducing the bacterial burden could potentially improve patient outcomes and reduce disease progression.

Secondary objectives include:

• Evaluating the efficacy of Gremubamab on **Pseudomonas aeruginosa** bacterial burden in sputum.
• Determining the persistent effects of Gremubamab on **Pseudomonas aeruginosa** bacterial burden following discontinuation of treatment at week 24.
• Assessing if Gremubamab can achieve eradication of **Pseudomonas aeruginosa** in some individuals.
• Determining the effect of Gremubamab on health-related quality of life.
• Evaluating the effect of Gremubamab on time to first exacerbation.
• Assessing the effect of Gremubamab on pulmonary function.
• Evaluating the safety of Gremubamab in patients with bronchiectasis.
• Evaluating the pharmacokinetics (PK) of Gremubamab.

The clinical trial involves a total of **60 participants** diagnosed with **bronchiectasis and chronic Pseudomonas aeruginosa infection**. The study population includes both male and female subjects, aged between 18 and 85 years. Participants were selected based on specific criteria, including a clinical diagnosis of bronchiectasis confirmed by a previous CT scan showing bronchiectasis in one or more lobes, and a history of P. aeruginosa presence in sputum or other airway samples within the past 24 months. All participants provided informed consent and were required to have a sputum sample that tested positive for P. aeruginosa at the screening visit and within 35 days of randomization. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity were highlighted in the selection process.

The clinical trial is designed to evaluate the efficacy of **gremubamab** in participants with bronchiectasis and chronic **Pseudomonas aeruginosa** infection. This is a phase II, randomized, double-blind, placebo-controlled trial. The trial aims to assess the impact of gremubamab on the bacterial burden of **Pseudomonas aeruginosa** in sputum at week 12. The trial is expected to run from November 21, 2023, to August 30, 2024, with recruitment starting on July 3, 2023, and ending on January 24, 2024.

Participants will be involved in the study for a maximum of 12 months. The study includes several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit. The screening visit will confirm eligibility based on criteria such as age (18 to 85 years), a clinical diagnosis of bronchiectasis, and a positive culture or PCR for **Pseudomonas aeruginosa**. Follow-up visits will occur at days 7, 14, 28, 56, 84, and 168 to monitor the primary and secondary endpoints, including bacterial load and other clinical outcomes. The end-of-study visit will conclude the participant's involvement in the trial.

Participants may be withdrawn from the study early if they experience adverse events, fail to comply with the study protocol, or withdraw consent. The investigational product, gremubamab, will be administered as a solution for infusion, with a maximum daily dose of 1500 mg and a total dose not exceeding 4500 mg over the treatment period. The trial will ensure that all procedures adhere to ethical standards and regulatory requirements, maintaining the integrity and scientific validity of the study.

The clinical trial involves the administration of **Gremubamab**, an experimental medication, which is provided in the form of a **solution for infusion**. The active substance, Gremubamab, is a protein of other origin. The pharmaceutical form is consistent across all sites, with the solution being administered via **intravenous infusion**. The dosing regimen includes a maximum daily dose of 1500 mg, with a total maximum dose of 4500 mg over a treatment period of up to 12 weeks. The administration schedule is designed to ensure optimal therapeutic levels while monitoring for any adverse effects. Compliance with the dosing schedule is monitored through regular assessments and documentation by the clinical trial team.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in this study. The placebo, identified as MEDI3902 PBO 4mL 10R, is administered either intramuscularly or intravenously, depending on the specific protocol requirements. The placebo is designed to match the experimental treatment in appearance and administration method to maintain the integrity of the double-blind study design. The use of a placebo allows for the assessment of the true efficacy and safety profile of Gremubamab by providing a baseline for comparison.

The efficacy of the investigational product **Gremubamab** will be assessed in a phase 2 clinical trial involving participants with bronchiectasis and chronic *Pseudomonas aeruginosa* infection. The primary endpoint for evaluating efficacy is the reduction in *Pseudomonas aeruginosa* bacterial burden in sputum at week 12. Secondary endpoints include various timepoints from baseline to days 7, 14, 28, 56, 84, and 168, as well as the first event from visit 1 to day 84. These endpoints will be measured using appropriate laboratory tests to quantify bacterial load in sputum samples.

The trial will involve the administration of **Gremubamab** via intravenous infusion, with a maximum daily dose of 1500 mg and a total maximum dose of 4500 mg over a 12-week treatment period. Efficacy assessments will be conducted at specified intervals throughout the trial duration, with the primary endpoint being evaluated at day 84. The data collected will be analyzed to determine the impact of **Gremubamab** on the bacterial burden compared to placebo, providing insights into its potential therapeutic benefits for patients with bronchiectasis and chronic *Pseudomonas aeruginosa* infection.