Efficacy and Safety Evaluation of Verekitug (UPB-101) in Moderate-to-Severe Chronic Obstructive Pulmonary Disease: A Phase 2b Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to assess the effect of **verekitug** on exacerbations in participants with moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD). This is clinically relevant as COPD exacerbations significantly impact patient morbidity and healthcare utilization, and effective management can improve patient outcomes and reduce healthcare costs.

Secondary objectives include:

• To assess the effect of verekitug on lung function assessments.
• To evaluate the impact of verekitug on severe COPD exacerbations.
• To determine the effect of verekitug on health-related quality of life.
• To assess the safety of verekitug in participants with COPD.
• To evaluate the pharmacokinetics (PK) of verekitug.
• To assess the immunogenicity of verekitug.

The clinical trial involves a total of **379 participants** diagnosed with **Moderate-to-Severe Chronic Obstructive Pulmonary Disease (COPD)**. The study population includes both male and female subjects, aged between **40 and 85 years**. Participants were selected based on specific criteria, including a physician diagnosis of COPD for more than 12 months and a history of smoking with at least 10 pack-years. The trial excludes vulnerable populations. Participants are required to have a post-bronchodilator FEV1/FVC ratio of less than 0.70 and a predicted post-bronchodilator FEV1 between 30% and 80%. They must also have a documented history of more than two moderate or more than one severe exacerbation within the year prior to inclusion. All participants are on background triple therapy (ICS, LABA, LAMA) for at least three months before randomization, with a stable dose of medications for one or more months prior to the first visit. Compliance with background therapy must be greater than 80% for at least four consecutive weeks during the screening period. The trial does not focus on any specific lifestyle considerations such as diet or physical activity.

The clinical trial is a **Phase 2b randomized, double-blind, placebo-controlled, parallel-group study** designed to assess the efficacy and safety of **Verekitug (UPB-101)** in participants with moderate-to-severe **Chronic Obstructive Pulmonary Disease (COPD)**. The primary objective is to evaluate the effect of Verekitug on COPD exacerbations. The trial will involve a total treatment period of 108 weeks, with the estimated recruitment start date in August 2025 and an estimated end date in March 2027.

Participants will be randomly assigned to receive either the active treatment, Verekitug, or a placebo, administered via **subcutaneous injection**. The study will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess final outcomes. The inclusion criteria require participants to be aged between 40 and 85 years, have a physician diagnosis of COPD for more than 12 months, and meet specific pulmonary function and exacerbation history requirements. Participants must also be on stable background therapy for COPD prior to randomization.

The expected length of participant involvement is approximately 108 weeks, during which they will be monitored for changes in pre-bronchodilator FEV1, the annualized rate of COPD exacerbations, and quality of life measures such as the St. George’s Respiratory Questionnaire (SGRQ) score. Safety will be assessed through the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), as well as the monitoring of serum concentrations of Verekitug and the presence of anti-drug antibodies (ADAs).

Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with study procedures, or if the investigator deems it necessary for their safety. The study aims to provide valuable data on the potential benefits of Verekitug in managing COPD exacerbations and improving patient outcomes.

The clinical trial involves the administration of **Verekitug (UPB-101)**, an experimental medication designed to assess its efficacy and safety in participants with moderate-to-severe **Chronic Obstructive Pulmonary Disease (COPD)**. Verekitug (UPB-101) is a **human IgG1 kappa monoclonal antibody against CRLF2**, formulated as a solution for injection. The pharmaceutical form is a solution intended for subcutaneous injection. The maximum daily dose is 400 mg, with a total maximum dose of 1800 mg over a treatment period of up to 108 days. The administration schedule and dosing are carefully monitored to ensure participant compliance and safety throughout the trial.

In addition to the experimental treatment, a placebo is utilized as a comparator to evaluate the efficacy of Verekitug (UPB-101). The placebo is referred to as **Verekitug (UPB-101) Placebo** and is included in the study to maintain the double-blind nature of the trial. The placebo does not contain any active substance and is administered in a manner consistent with the experimental treatment to ensure blinding is maintained. The use of a placebo allows for a controlled assessment of the treatment's effects on COPD exacerbations.

The efficacy of Verekitug (UPB-101) in participants with moderate-to-severe **Chronic Obstructive Pulmonary Disease (COPD)** will be assessed through a Phase 2b randomized, double-blind, placebo-controlled, parallel-group study. The primary endpoint for evaluating efficacy is the annualized rate of moderate or severe COPD exacerbation events compared with placebo over a treatment period of 108 weeks. Secondary endpoints include the change in pre-bronchodilator FEV1 from baseline to Week 60, the annualized rate of severe COPD exacerbation events over 108 weeks, and the change in St. George’s Respiratory Questionnaire (SGRQ) total score from baseline to Week 60. Additionally, the proportion of participants with an SGRQ improvement of more than 4 points at Week 60 will be assessed.

Other secondary endpoints involve the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), serum concentrations of Verekitug, its pharmacokinetic (PK) profile, and the incidence of anti-drug antibodies (ADAs) during the study, including the post-treatment follow-up period. These efficacy parameters will be measured and collected at specified timepoints, such as baseline, Week 60, and throughout the 108-week treatment period, using validated scales and laboratory tests. The study aims to provide comprehensive data on the efficacy and safety of Verekitug in the target population.