Tezepelumab COPD Exacerbation Study

Study Overview
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Brief Summary
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A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 2a Study to Explore the Efficacy and Safety of Tezepelumab in Adults with Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD)

Detailed Description
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This is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety and efficacy of tezepelumab in adults with moderate to very severe chronic obstructive pulmonary disease (COPD) receiving triple inhaled maintenance therapy, and having had 2 or more documented COPD exacerbations in the 12 months prior to Visit 1. Approximately, 338 subjects will be randomized globally. Subjects will be stratified by region and prior number of exacerbations (2 vs. 3 or more). Subjects will receive tezepelumab, or placebo, administered via subcutaneous injection at the study site, over a 52 week treatment period. The study also includes a post-treatment follow-up period of 12 weeks.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Phase 2a Study to Explore the Efficacy and Safety of Tezepelumab in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) (COURSE)

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Biological: Tezepelumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of moderate to very severe physician-diagnosed COPD for at least 12 months prior to enrolment with a post-bronchodilator FEV1/FVC<0.70 and a post-bronchodilator FEV1 ≥20% and ≤80% of predicted normal value. History of at least 2 documented moderate to severe COPD exacerbations within 2 to 52 weeks prior to enrollment. CAT score of ≥15 at enrollment and on day of randomization. Documented treatment with triple therapy for COPD (medium or high dose ICS/LABA/LAMA) throughout the year prior to enrollment. The dose of ICS should be stable for 3 months prior to enrollment. Exclusion Criteria: Clinically important pulmonary disease other than COPD, as judged by the Investigator (including current or historic asthma diagnosis). Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious (including risk factors for pneumonia), endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable. Major surgery within 8 weeks before enrollment. History of clinically significant infection requiring antibiotics or antiviral medication within 14 days before enrollment. Pregnant or breastfeeding. The chest/lungs with pathology that precludes the patient's ability to complete the study The patient has active COVID 19 infection during screening period.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tezepelumab<br>Tezepelumab, SC, Q4W | Biological: Tezepelumab<br>* Tezepelumab subcutaneous injection<br>|
| Placebo Comparator: Matching Placebo<br>Matching placebo, SC, Q4W | Other: Placebo<br>* Placebo subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Moderate or severe COPD exacerbation rate ratio (tezepelumab vs placebo) | The exacerbation rate is based on exacerbations reported by the investigator over 52 weeks. | Over 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first moderate or severe COPD exacerbation | Time to first occurrence of moderate/severe exacerbation post randomization. Outcome measures: Hazard ratio | By Week 52 | 
| Proportion with at least one moderate/severe COPD exacerbation | Proportion of subjects with at least one moderate/severe exacerbation reported by the Investigator over 52 weeks Outcome measure: Odds Ratio | Over 52 Weeks | 
| Severe COPD exacerbation rate ratio (tezepelumab vs. placebo) | The severe exacerbation rate is based on severe exacerbations reported by the Investigator over 52 weeks. | Over 52 Weeks | 
| Change from baseline in pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) | Difference in change from baseline in pre-BD forced expiratory volume in 1 second (FEV1) in tezepelumab arm as compared to placebo at Week 52. FEV1 is defined as the volume of air exhaled from the lungs in the first second of forced expiration. | Baseline, Week 52 | 
| Change in respiratory health status/health-related quality of life | Proportion of subjects achieving a decrease of 4 units or more in the St. George's Respiratory Questionnaire (SGRQ) total score at Week 52, i.e. minimum clinically important difference (MCID). Outcome measure: odds ratio | Baseline, Week 52 | 
| Change from baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score | Difference (tezepelumab vs. placebo) in SGRQ from baseline at Week 52. SGRQ is a 50-item patient reported outcome questionnaire. The SGRQ total score is expressed as a percentage of overall impairment, in which 100% means the worst possible health status and 0% indicates the best possible health status. Likewise, the domain scores range from 0 to 100, with higher scores indicative of greater impairment. Decrease of 4 units is associated with a minimum clinically important difference (MCID). | Baseline, Week 52 | 
| Change from baseline in the COPD Assessment Test (CAT) Total Score | Difference (tezepelumab vs. placebo) in COPD assessment tool (CAT) from baseline at Week 52. CAT is an 8-item patient reported outcome questionnaire developed to measure the impact of COPD on health status. The instrument uses semantic differential six-point response scales. A CAT total score is the sum of item responses. The score ranges from 0 to 40, with higher scores indicating greater COPD impact on health status. | Baseline, Week 52 | 
| Evaluate pharmacokinetics of tezepelumab | Serum trough concentration of tezepelumab | Weeks 0, 4, 12, 24, 36, 52, 64 | 
| Evaluate immunogenicity of tezepelumab | Incidence of anti-drug antibodies (ADA) | Over 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Moderate COPD, Severe COPD, chronic obstructive pulmonary disease