Efficacy and Safety Evaluation of Tezepelumab in Adults with Moderate to Very Severe Chronic Obstructive Pulmonary Disease: A Phase III Randomized Controlled Trial

The primary objective of this study is to compare the effect of **tezepelumab** with placebo on moderate or severe exacerbations in participants with moderate to very severe **chronic obstructive pulmonary disease (COPD)**. This is clinically relevant as exacerbations significantly impact the morbidity and mortality associated with COPD, and effective management can improve patient outcomes and reduce healthcare utilization.

Secondary objectives include:

• Comparing the effect of tezepelumab with placebo on pre-bronchodilator lung function in participants with moderate to very severe COPD.
• Assessing the impact on health-related quality of life (HRQL) using the St. George's Respiratory Questionnaire (SGRQ) total score and responder status.
• Evaluating the effect on moderate or severe COPD exacerbations in participants with screening eosinophil counts ≥300 cells/μL.
• Investigating the effect on severe COPD exacerbations.
• Assessing the impact on COPD health status using the COPD Assessment Test (CAT) total score and responder status.
• Comparing the time to first moderate to severe COPD exacerbation and time to first severe exacerbation.
• Exploring the effect on post-bronchodilator lung function.
• Evaluating the pharmacokinetics (PK) and immunogenicity of tezepelumab in this patient population.

The clinical trial involves a total of **805 participants** diagnosed with **chronic obstructive pulmonary disease (COPD)**. The study population comprises both male and female adults aged between 40 and 80 years. Participants were selected based on a documented physician diagnosis of COPD for at least 12 months prior to the study, with specific lung function criteria and a history of COPD exacerbations. All participants are either current or former smokers with a history of at least 10 pack-years of tobacco smoking. The trial includes individuals who are on a regular dose of inhaled therapy and have a **COPD Assessment Test (CAT)** score of 15 or higher. The study population is considered vulnerable, and lifestyle factors such as smoking history are significant considerations in the selection process.

The clinical trial is a **randomized**, **double-blind**, **placebo-controlled**, parallel-group, multicenter, Phase III study designed to evaluate the efficacy and safety of **tezepelumab** in adult participants with moderate to very severe **chronic obstructive pulmonary disease (COPD)**. The primary objective is to compare the effect of tezepelumab with placebo on moderate or severe COPD exacerbations. The trial is expected to last for approximately 76 weeks, with an estimated recruitment start date in June 2025 and an estimated end date in January 2028.

Participants will be randomly assigned to receive either tezepelumab or a placebo, administered via **subcutaneous injection**. The study will include several key visits: an inclusion (screening) visit, multiple follow-up visits, and an end-of-study visit. During the screening visit, eligibility will be assessed based on criteria such as age (40 to 80 years), documented physician-diagnosed COPD, and a history of COPD exacerbations. Follow-up visits will occur periodically to monitor the participants' health status, collect data on primary and secondary endpoints, and ensure adherence to the study protocol. The end-of-study visit will conclude the trial, with final assessments and data collection.

Participant involvement is expected to last for the entire duration of the trial, approximately 76 weeks. However, conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or any adverse events that may compromise participant safety. The primary endpoint is the annualized rate of moderate or severe COPD exacerbations up to 76 weeks. Secondary endpoints include changes from baseline in pre-bronchodilator FEV1, SGRQ total score, and CAT total score over 52 weeks, among others. The study will also assess pharmacokinetics and immunogenicity, including serum trough concentrations and the incidence of anti-drug antibodies.

The clinical trial involves the administration of **Tezepelumab**, marketed under the name Tezspire, which is a **solution for injection** provided in a pre-filled syringe. The active substance, tezepelumab, is a protein-based therapeutic agent classified under the ATC code R03DX11. The pharmaceutical form is a solution for injection, and the medication is administered via **subcutaneous injection**. Each syringe contains 210 mg of tezepelumab. The treatment is designed to be administered at a frequency determined by the study protocol, with a maximum treatment period of 76 weeks. The investigational medicinal product has different manufacturing, packaging, and labeling sites than those specified in the marketing authorization. Compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol.

The study also includes a **placebo** group, where participants receive a placebo treatment designed to mimic the administration of tezepelumab. The placebo is referred to as Tezepelumab-placebo and is used to maintain the double-blind nature of the trial. The placebo does not contain any active substance and is administered in the same manner as the active treatment, ensuring that neither the participants nor the investigators are aware of the treatment allocation. This allows for an unbiased comparison of the efficacy and safety of tezepelumab in reducing moderate or severe exacerbations in participants with moderate to very severe **Chronic Obstructive Pulmonary Disease (COPD)**.

The efficacy of Tezepelumab in the treatment of moderate to very severe **Chronic Obstructive Pulmonary Disease (COPD)** will be assessed through a randomized, double-blind, placebo-controlled, parallel-group, multicenter Phase III clinical trial. The primary endpoint for evaluating efficacy is the annualized rate of moderate or severe COPD exacerbations over a period of up to 76 weeks. Secondary endpoints include changes from baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) at Week 52, changes in the St. George's Respiratory Questionnaire (SGRQ) total score over 52 weeks, and the annualized rate of moderate or severe COPD exacerbations among participants with screening eosinophil counts of ≥300 cells/μL. Additional secondary endpoints involve the time to first moderate to severe COPD exacerbation, changes in the COPD Assessment Test (CAT) total score, and pharmacokinetic and immunogenicity assessments, including serum trough concentrations and the incidence of anti-drug antibodies.

Efficacy parameters will be measured and collected at specified time points, including baseline, Week 52, and up to 76 weeks. Validated scales such as the SGRQ and CAT will be utilized to assess patient-reported outcomes. The analysis will focus on determining the effect of Tezepelumab compared to placebo in reducing the frequency and severity of COPD exacerbations and improving lung function and quality of life in the study population. The trial is designed to provide comprehensive data on the efficacy of Tezepelumab in managing COPD symptoms and exacerbations.