A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ASTEGOLIMAB IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

The primary objective of this study is to evaluate the **efficacy** of astegolimab compared with placebo in patients with **Chronic Obstructive Pulmonary Disease (COPD)**. This is assessed based on the annualized rate of moderate and severe COPD exacerbations over a 52-week treatment period. This objective is clinically relevant as it aims to determine the potential of astegolimab to reduce the frequency of exacerbations, which are critical events in the management of COPD, often leading to hospitalizations and increased healthcare utilization.

Secondary objectives include:

• Evaluating the efficacy of astegolimab compared with placebo based on the time to first moderate or severe COPD exacerbation during the 52-week treatment period.
• Assessing the efficacy based on absolute change from baseline in health-related quality of life (HRQoL) at Week 52, post-bronchodilator forced expiratory volume in 1 second (FEV1), and Evaluating Respiratory Symptoms in COPD (E-RS:COPD) total score at Week 52.
• Determining the proportion of participants with improvement in HRQoL, defined as a decrease from baseline of ≥ 4 points in SGRQ-C total score, at Week 52.
• Evaluating the efficacy based on the annualized rate of severe COPD exacerbations over the 52-week treatment period.
• Assessing the safety of astegolimab compared with placebo.
• Characterizing the pharmacokinetic (PK) profile of astegolimab.
• Evaluating the immune response to astegolimab.
• Assessing the efficacy based on the annualized rate of moderate and severe COPD exacerbations over the 52-week treatment period.

The clinical trial involves a total of **515 participants** diagnosed with **Chronic Obstructive Pulmonary Disease (COPD)**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific criteria, including a documented COPD diagnosis for at least 12 months and a history of frequent exacerbations. The trial includes individuals who are current or former tobacco smokers with a significant smoking history. All participants are on optimized COPD maintenance therapy. The study does not exclude vulnerable populations, ensuring a comprehensive evaluation of the treatment's efficacy across diverse demographic groups.

The clinical trial is a **Phase III**, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of **astegolimab** in patients with **Chronic Obstructive Pulmonary Disease (COPD)**. The primary objective is to assess the efficacy of astegolimab compared to placebo based on the annualized rate of moderate and severe COPD exacerbations over a 52-week treatment period. The trial will involve the administration of astegolimab as a **solution for injection** via the **subcutaneous** route, utilizing a pre-filled syringe with a needle-safety device. The study is expected to commence recruitment on June 30, 2023, and conclude by October 10, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a documented COPD diagnosis for at least 12 months, a history of frequent exacerbations, and specific lung function parameters. Following the screening, eligible participants will be randomized to receive either astegolimab or placebo. The trial will include regular follow-up visits to monitor the participants' health status, collect data on exacerbations, and assess any treatment-emergent adverse events. The end-of-study visit will occur at the conclusion of the 52-week treatment period, where final assessments will be conducted, including the evaluation of health-related quality of life and lung function changes.

The expected length of participant involvement is approximately 52 weeks, with conditions for early termination including the occurrence of serious adverse events, withdrawal of consent, or any other medical reasons deemed necessary by the investigator. The study will adhere to rigorous methodological standards to ensure the reliability and validity of the findings, contributing valuable insights into the management of COPD with astegolimab.

The clinical trial involves the administration of **Astegolimab**, a monoclonal antibody, as the experimental medication. Astegolimab is provided in the form of a **solution for injection**. The administration route is **subcutaneous**, utilizing a pre-filled syringe equipped with a needle-safety device, specifically the BD UltraSafe Passive. The dosing schedule is designed to evaluate the efficacy and safety of Astegolimab over a 52-week treatment period in patients with chronic obstructive pulmonary disease (COPD). The maximum treatment period is set at 50 weeks, with the dosage measured in milligrams, although specific dosing amounts are not detailed in the provided data. Compliance with the dosing regimen is monitored throughout the study to ensure adherence to the protocol.

The study also includes a **placebo** group, which receives an injection that mimics the administration of Astegolimab but contains no active substance. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. This control group is essential for accurately assessing the efficacy of Astegolimab by comparing the outcomes against those receiving the placebo. The placebo is administered using the same subcutaneous route and device as the active treatment to maintain consistency across the study arms.

The efficacy of **astegolimab** in patients with Chronic Obstructive Pulmonary Disease (COPD) will be assessed in a Phase III, randomized, double-blind, placebo-controlled, multicenter study. The primary endpoint for evaluating efficacy is the annualized rate of moderate and severe COPD exacerbations over a 52-week treatment period. Secondary endpoints include the time to first moderate or severe COPD exacerbation during the 52-week treatment period, absolute change from baseline in Health-Related Quality of Life (HRQoL) at Week 52 as assessed through the St. George's Respiratory Questionnaire for COPD patients (SGRQ-C) total score, and absolute change from baseline in post-bronchodilator Forced Expiratory Volume in one second (FEV1) at Week 52.

Additional secondary endpoints involve the absolute change from baseline in the Evaluating Respiratory Symptoms in COPD (E-RS:COPD) total score at Week 52, the proportion of participants with improvement in HRQoL defined as a decrease from baseline of ≥4 points in SGRQ-C total score at Week 52, and the annualized rate of severe COPD exacerbations over the 52-week treatment period. The incidence and severity of all treatment-emergent adverse events (TEAEs), including Serious Adverse Events (SAEs), adverse events of special interest (AESIs), and TEAEs leading to death or discontinuation, will also be monitored. Changes from baseline in selected vital signs, clinical laboratory test results, and electrocardiograms (ECGs) will be evaluated, along with serum concentration of astegolimab at specified timepoints and the prevalence and incidence of anti-drug antibodies (ADAs) during the study.