Efficacy and Safety Evaluation of Tezepelumab in Adults with Moderate to Very Severe Chronic Obstructive Pulmonary Disease: A Randomized, Double-Blind, Placebo-Controlled Study

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

The clinical trial involves a total of **700 participants** diagnosed with **Chronic Obstructive Pulmonary Disease (COPD)**. The study population comprises adults aged between **40 to 80 years**, including both male and female subjects. Participants were selected based on specific criteria, including a documented physician-diagnosed COPD for at least 12 months prior to the study, and a history of at least two moderate or one severe COPD exacerbations within the previous year. All participants are either current or former smokers with a history of at least 10 pack-years of tobacco smoking. The trial excludes vulnerable populations and focuses on individuals who have been on a regular dose of inhaled therapy for at least three consecutive months before the study. Lifestyle considerations such as smoking history are significant, as participants must have ceased smoking for at least six months prior to the trial. The study aims to compare the effect of tezepelumab with placebo on moderate or severe COPD exacerbations in individuals with moderate to very severe COPD.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled, parallel group, multicentre, Phase III study** 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 until April 2029, with recruitment starting in June 2025. Participants will be involved for a maximum treatment period of 72 weeks, with the primary endpoint being the annualized rate of moderate or severe COPD exacerbations up to 76 weeks.

The study will commence with an inclusion (screening) visit, where eligibility will be assessed based on criteria such as age (40 to 80 years), documented physician-diagnosed COPD, and a history of smoking. Participants must have a documented history of COPD exacerbations and be on regular inhaled therapy. Following the screening, eligible participants will be randomized to receive either tezepelumab or placebo via subcutaneous injection. Study visits will occur at regular intervals to monitor safety, efficacy, and any adverse events. Key follow-up visits will include assessments of lung function, quality of life scores, and exacerbation rates.

The end-of-study visit will conclude the participant's involvement, where final assessments will be conducted to evaluate the long-term effects of the treatment. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or withdraw consent. The study will also monitor secondary endpoints, including changes in lung function and quality of life scores over 52 weeks, and the incidence of anti-drug antibodies. The trial is not classified as low intervention, and the investigational product, Tezspire, is administered in a pre-filled syringe for subcutaneous injection.

The clinical trial involves the administration of **Tezepelumab**, marketed under the name Tezspire, which is a **solution for injection** 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, specifically designed for subcutaneous administration. Each pre-filled syringe contains 210 mg of tezepelumab. The administration schedule involves subcutaneous injections, with a maximum treatment period of 72 weeks. The product is manufactured by AstraZeneca AB and has been authorized for use in the European Union under the marketing authorization number EU/1/22/1677/001. The investigational medicinal product (IMP) has different manufacturing, packaging, and labeling sites than those specified in the marketing authorization.

The study also includes a **placebo** comparator, referred to as Tezepelumab-placebo. This placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators know which treatment is being administered. The placebo is designed to match the appearance and administration route of the active treatment, although it contains no active substance. The placebo is administered in the same manner as the active treatment, via subcutaneous injection, to ensure consistency in the study protocol.

The efficacy of **tezepelumab** in the treatment of moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) will be assessed in 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 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 up to 76 weeks. Additional secondary endpoints involve the time to first moderate to severe COPD exacerbation, time to first severe COPD exacerbation, and changes from baseline in the COPD Assessment Test (CAT) total score over 52 weeks.

Measurements will be collected at specified time points, including Week 52 and up to 76 weeks, using validated scales and laboratory tests. The SGRQ and CAT scores will be used to assess patient-reported outcomes, while FEV1 will be measured through spirometry. The trial will also evaluate pharmacokinetics by measuring serum trough concentrations and assess immunogenicity through the incidence of anti-drug antibodies and neutralizing antibodies. The data collected will be analyzed to determine the efficacy of tezepelumab compared to placebo in reducing COPD exacerbations and improving lung function and quality of life in the study population.