Tezepelumab COPD Exacerbation Study (COURSE)

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)

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)

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Other: Placebo; Biological: Tezepelumab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 337
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Research Site
  • Quebec, Canada, G3K 2P8
    • Research Site
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Research Site
    • Sherwood Park, Alberta, Canada, T8L 0N2
      • Research Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Research Site
  • Nova Scotia
    • Truro, Nova Scotia, Canada, B2N 1L2
      • Research Site
  • Ontario
    • Burlington, Ontario, Canada, L7N 3V2
      • Research Site
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Research Site
  • Quebec
    • Montréal, Quebec, Canada, H1M 1B1
      • Research Site
    • St Charles Borromee, Quebec, Canada, J6E 2B4
      • Research Site
    • Trois-Rivières, Quebec, Canada, G8T 7A1
      • Research Site
• Denmark
  • Aarhus N, Denmark, 8200
    • Research Site
  • Hvidovre, Denmark, 2650
    • Research Site
  • København NV, Denmark, 2400
    • Research Site
  • Odense C, Denmark, 5000
    • Research Site
  • Roskilde, Denmark, 4000
    • Research Site
  • Vejle, Denmark, 7100
    • Research Site
  • Ålborg, Denmark, 9000
    • Research Site
• France
  • Amiens Cedex 1, France, 80054
    • Research Site
  • Brest Cedex 2, France, 29609
    • Research Site
  • Grenoble Cedex, France, 38043
    • Research Site
  • Lyon Cedex 04, France, 69317
    • Research Site
  • Marseille, France, 13015
    • Research Site
  • Montpellier, France, 34090
    • Research Site
  • Nantes Cedex 1, France, 44093
    • Research Site
• Germany
  • Berlin, Germany, 12203
    • Research Site
  • Frankfurt, Germany, 60596
    • Research Site
  • Grosshansdorf, Germany, 20927
    • Research Site
  • Lübeck, Germany, 23552
    • Research Site
  • Mainz, Germany, 55131
    • Research Site
• Israel
  • Ashkelon, Israel, 7830604
    • Research Site
  • Beer Sheva, Israel, 84101
    • Research Site
  • Haifa, Israel, 34362
    • Research Site
  • Jerusalem, Israel, 91031
    • Research Site
  • Jerusalem, Israel, 91120
    • Research Site
  • Kfar Saba, Israel, 49281
    • Research Site
  • Rehovot, Israel, 7661041
    • Research Site
• Korea, Republic of
  • Daegu, Korea, Republic of, 42415
    • Research Site
  • Incheon, Korea, Republic of, 21431
    • Research Site
  • Jeonju-si, Korea, Republic of, 54907
    • Research Site
  • Seoul, Korea, Republic of, 03722
    • Research Site
  • Seoul, Korea, Republic of, 05505
    • Research Site
  • Seoul, Korea, Republic of, 06591
    • Research Site
  • Seoul, Korea, Republic of, 03312
    • Research Site
  • Seoul, Korea, Republic of, 05030
    • Research Site
  • Seoul, Korea, Republic of, 06973
    • Research Site
  • Uijeongbu-si, Korea, Republic of, 11765
    • Research Site
• Netherlands
  • Eindhoven, Netherlands, 5623 EJ
    • Research Site
  • Heerlen, Netherlands, 6419 PC
    • Research Site
  • Rotterdam, Netherlands, 3045 PM
    • Research Site
  • Rotterdam, Netherlands, 3083 AN
    • Research Site
  • Zutphen, Netherlands, 7207 AE
    • Research Site
• Spain
  • Alzira, Spain, 46410
    • Research Site
  • Barcelona, Spain, 08025
    • Research Site
  • Granada, Spain, 18014
    • Research Site
  • Málaga, Spain, 29010
    • Research Site
  • Mérida (Badajoz), Spain, 06800
    • Research Site
• United Kingdom
  • Bradford, United Kingdom, BND9 6RJ
    • Research Site
  • Chertsey, United Kingdom, KT16 0PZ
    • Research Site
  • Cottingham, United Kingdom, HU16 5JQ
    • Research Site
  • Glasgow, United Kingdom, G12 0YN
    • Research Site
  • London, United Kingdom, SW10 9NH
    • Research Site
  • Newcastle-upon-Tyne, United Kingdom, NE1 4LP
    • Research Site
  • Wakefield, United Kingdom, WF1 4DG
    • Research Site
• United States
  • Alabama
    • Dothan, Alabama, United States, 36305
      • Research Site
  • California
    • Huntington Beach, California, United States, 92647
      • Research Site
    • Newport Beach, California, United States, 92663
      • Research Site
    • Upland, California, United States, 91786
      • Research Site
    • Westminster, California, United States, 92683
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Research Site
  • Florida
    • Brandon, Florida, United States, 33511
      • Research Site
    • Orlando, Florida, United States, 32819
      • Research Site
    • Panama City, Florida, United States, 32405
      • Research Site
    • Tampa, Florida, United States, 33607
      • Research Site
    • Winter Park, Florida, United States, 32789-4681
      • Research Site
  • Michigan
    • Buckley, Michigan, United States, 49620
      • Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • Research Site
    • Mooresville, North Carolina, United States, 28117
      • Research Site
    • New Bern, North Carolina, United States, 28562
      • Research Site
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Research Site
  • Oklahoma
    • Edmond, Oklahoma, United States, 73034
      • Research Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Research Site
    • Pittsburgh, Pennsylvania, United States, 15213
      • Research Site
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Research Site
    • Rock Hill, South Carolina, United States, 29732
      • Research Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Research Site
  • Texas
    • McKinney, Texas, United States, 75069
      • Research Site
  • Virginia
    • Abingdon, Virginia, United States, 24210
      • Research Site
  • Washington
    • Everett, Washington, United States, 98208
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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.
2. History of at least 2 documented moderate to severe COPD exacerbations within 2 to 52 weeks prior to enrollment.
3. CAT score of ≥15 at enrollment and on day of randomization.
4. 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:

1. Clinically important pulmonary disease other than COPD, as judged by the Investigator (including current or historic asthma diagnosis).
2. 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.
3. Major surgery within 8 weeks before enrollment.
4. History of clinically significant infection requiring antibiotics or antiviral medication within 14 days before enrollment.
5. Pregnant or breastfeeding.
6. The chest/lungs with pathology that precludes the patient's ability to complete the study
7. The patient has active COVID 19 infection during screening period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tezepelumab; Tezepelumab, SC, Q4W	Biological: Tezepelumab; Tezepelumab subcutaneous injection
Placebo Comparator: Matching Placebo; Matching placebo, SC, Q4W	Other: Placebo; Placebo subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Moderate or Severe COPD Exacerbations in Participants With Moderate to Very Severe COPD.	A COPD exacerbation was defined as a change in the participant's usual COPD symptoms that is beyond normal day-to-day variation, is acute in onset, lasts 2 or more days, and may warrant a change in regular medication and leads to any of the following: Use of systemic corticosteroids for at least 3 days, use of antibiotics for at least 3 days, an inpatient hospitalisation due to COPD, or results in death. Analysis was done using a negative binomial model with the response variable as the number of COPD exacerbations experienced during the follow-up for exacerbations. The model included covariates of treatment group, region, and number of exacerbations reported at randomisation as recorded in IWRS (2, >=3). The logarithm of the time at risk (in years) for exacerbation in the study is used as an offset variable.	From randomisation up to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Moderate/Severe COPD Exacerbation	Time to first moderate/severe COPD exacerbation post-randomisation, presented as number of subjects with at least one moderate/severe COPD exacerbation.	From randomisation up to Week 52
Proportion of Participants COPD Exacerbation Free at Week 52	An exacerbation event was defined as described in primary analysis. A participant was exacerbation free if they did not experience any moderate or severe exacerbations from randomisation to Week 52 (EOT).	From randomisation up to Week 52
Comparison of Annual Severe COPD Exacerbation Rates Over 52 Weeks	An exacerbation was considered severe if it results in at least 1 of the following: Hospitalisation due to the COPD exacerbation (defined as a participant being admitted for ≥ 24 hours to an observation area, the emergency department, or other equivalent healthcare facility), or death related to COPD or COPD exacerbation.	From randomisation up to Week 52
Proportion of Participants With >=1 Severe COPD Exacerbations Over 52 Weeks	An exacerbation was considered severe if it results in at least 1 of the following: Hospitalisation due to the COPD exacerbation (defined as a participant being admitted for ≥ 24 hours to an observation area, the emergency department, or other equivalent healthcare facility), or death related to COPD or COPD exacerbation.	From randomisation up to Week 52
Time to First Severe COPD Exacerbation	Time to first severe COPD exacerbation post-randomisation, presented as number of subjects with at least one severe COPD exacerbation.	From randomisation up to Week 52
Least Square (LS) Mean Difference in Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 (FEV1) at Week 52	Pre-Bronchodilator FEV1 (L) was determined by spirometry at the clinic visit. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration. Change from baseline was obtained as an absolute difference between Week 52 measure and the baseline value. Baseline was defined as the last assessment recorded prior to the first dose of study treatment.	Baseline and Week 52
Lease Square (LS) Mean Difference in Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 52	The SGRQ is a 50-item PRO instrument to measure the health status of participants with airway obstruction diseases. The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status. Baseline is the measurement recorded at Week 0 (Visit 3).	Baseline and Week 52
Proportion of Participants Achieving a Minimum Clinically Important Difference of 4 Units or More in St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 52	The SGRQ is a 50-item PRO instrument to measure the health status of participants with airway obstruction diseases. The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status. A responder was defined as an individual who had "improvement" at Week 52 (>=4 point decrease in SGRQ total score).	Baseline and Week 52
Least Square (LS) Mean Difference in Change From Baseline in COPD Assessment Tool (CAT) Total Score at Week 52	The CAT is an 8-item PRO developed to measure the impact of COPD on health status. A CAT total score is the sum of item responses. Scores range from 0-40 with higher scores indicative of greater COPD impact on health status. Baseline was defined as the value at the randomisation visit (Visit 3). If the Visit 3 measurement was missing, the screening value was used as baseline instead.	Baseline and Week 52
Serum Concentration of Tezepelumab	Blood samples were collected to determine the serum concentration of Tezepelumab. With the exception of Week 0 and Week 64, only pre-dose data from samples collected between 21 and 35 days after previous dose of investigational product were included.	Pre-dose at weeks 0, 4, 12, 24, 36 and also at weeks 52 and 64 where no dosing was scheduled
Number of Participants With Anti-Drug Antibody (ADA) Response to Tezepelumab	Blood samples were measured for the presence of ADAs for tezepelumab using validated assays. Treatment-induced ADA positive was defined as ADA negative at baseline and post-baseline ADA positive. Treatment-boosted ADA positive was defined as baseline positive ADA titre that was boosted to a 4 fold or higher level following IP administration. TE-ADA positive was defined as the sum of treatment-induced ADA positive and treatment-boosted ADA positive. ADA incidence is the proportion of TE-ADA positive subjects in a population. ADA persistently positive was defined as ADA positive at >= 2 post-baseline assessments or ADA positive at last post-baseline assessment. ADA transiently positive was defined as having at least one post-baseline ADA positive assessment and not fulfilling the conditions of ADA persistently positive. Treatment-induced nAb positive was defined as nAb negative or ADA negative at baseline and nAb positive at any post-baseline visit.	Pre-dose at weeks 0, 4, 12, 24, 36 and also at weeks 52 and 64 where no dosing was scheduled

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Amgen
• Investigators: Principal Investigator: Dave Singh, MD, Division of Infection, Immunity & Resp Medicine, The University of Manchester, United Kingdom

Publications and helpful links

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2019
• Primary Completion (Actual): November 10, 2023
• Study Completion (Actual): January 31, 2024

Study Registration Dates

• First Submitted: July 29, 2019
• First Submitted That Met QC Criteria: July 29, 2019
• First Posted (Actual): July 31, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 17, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: COPD; chronic obstructive pulmonary disease; Moderate COPD; Severe COPD
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: D5241C00001; 2019-001363-67 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes