Clinical trial NCT04039113: Tezepelumab COPD Exacerbation Study
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Keywords: COPD
Moderate COPD
Severe COPD
chronic obstructive pulmonary disease
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2019-07-31
Enrollment: 337
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Rate of Moderate or Severe COPD Exacerbations in Participants With Moderate to Very Severe COPD.
timeFrame: From randomisation up to Week 52
Secondary outcomes:
measure: Time to First Moderate/Severe COPD Exacerbation
timeFrame: From randomisation up to Week 52
measure: Proportion of Participants COPD Exacerbation Free at Week 52
timeFrame: From randomisation up to Week 52
measure: Comparison of Annual Severe COPD Exacerbation Rates Over 52 Weeks
timeFrame: From randomisation up to Week 52
measure: Proportion of Participants With >=1 Severe COPD Exacerbations Over 52 Weeks
timeFrame: From randomisation up to Week 52
measure: Time to First Severe COPD Exacerbation
timeFrame: From randomisation up to Week 52
measure: Least Square (LS) Mean Difference in Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 (FEV1) at Week 52
timeFrame: Baseline and Week 52
measure: Lease Square (LS) Mean Difference in Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 52
timeFrame: Baseline and Week 52
measure: 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
timeFrame: Baseline and Week 52
measure: Least Square (LS) Mean Difference in Change From Baseline in COPD Assessment Tool (CAT) Total Score at Week 52
timeFrame: Baseline and Week 52
measure: Serum Concentration of Tezepelumab
timeFrame: Pre-dose at weeks 0, 4, 12, 24, 36 and also at weeks 52 and 64 where no dosing was scheduled
measure: Number of Participants With Anti-Drug Antibody (ADA) Response to Tezepelumab
timeFrame: Pre-dose at weeks 0, 4, 12, 24, 36 and also at weeks 52 and 64 where no dosing was scheduled
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Research Site
state: Alabama
city: Huntington Beach
country: United States
facility: Research Site
state: California
city: Newport Beach
country: United States
facility: Research Site
state: California
city: Upland
country: United States
facility: Research Site
state: California
city: Westminster
country: United States
facility: Research Site
state: California
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Brandon
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Panama City
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Winter Park
country: United States
facility: Research Site
state: Florida
city: Buckley
country: United States
facility: Research Site
state: Michigan
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Mooresville
country: United States
facility: Research Site
state: North Carolina
city: New Bern
country: United States
facility: Research Site
state: North Carolina
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Edmond
country: United States
facility: Research Site
state: Oklahoma
city: Medford
country: United States
facility: Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Mount Pleasant
country: United States
facility: Research Site
state: South Carolina
city: Rock Hill
country: United States
facility: Research Site
state: South Carolina
city: Rapid City
country: United States
facility: Research Site
state: South Dakota
city: McKinney
country: United States
facility: Research Site
state: Texas
city: Abingdon
country: United States
facility: Research Site
state: Virginia
city: Everett
country: United States
facility: Research Site
state: Washington
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Sherwood Park
country: Canada
facility: Research Site
state: Alberta
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Truro
country: Canada
facility: Research Site
state: Nova Scotia
city: Burlington
country: Canada
facility: Research Site
state: Ontario
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Montréal
country: Canada
facility: Research Site
state: Quebec
city: St Charles Borromee
country: Canada
facility: Research Site
state: Quebec
city: Trois-Rivières
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Quebec
country: Canada
facility: Research Site
city: Aarhus N
country: Denmark
facility: Research Site
city: Hvidovre
country: Denmark
facility: Research Site
city: København NV
country: Denmark
facility: Research Site
city: Odense C
country: Denmark
facility: Research Site
city: Roskilde
country: Denmark
facility: Research Site
city: Vejle
country: Denmark
facility: Research Site
city: Ålborg
country: Denmark
facility: Research Site
city: Amiens Cedex 1
country: France
facility: Research Site
city: Brest Cedex 2
country: France
facility: Research Site
city: Grenoble Cedex
country: France
facility: Research Site
city: Lyon Cedex 04
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Nantes Cedex 1
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Grosshansdorf
country: Germany
facility: Research Site
city: Lübeck
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: Ashkelon
country: Israel
facility: Research Site
city: Beer Sheva
country: Israel
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Kfar Saba
country: Israel
facility: Research Site
city: Rehovot
country: Israel
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Jeonju-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Uijeongbu-si
country: Korea, Republic of
facility: Research Site
city: Eindhoven
country: Netherlands
facility: Research Site
city: Heerlen
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Zutphen
country: Netherlands
facility: Research Site
city: Alzira
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Granada
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Mérida (Badajoz)
country: Spain
facility: Research Site
city: Bradford
country: United Kingdom
facility: Research Site
city: Chertsey
country: United Kingdom
facility: Research Site
city: Cottingham
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Newcastle-upon-Tyne
country: United Kingdom
facility: Research Site
city: Wakefield
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Division of Infection, Immunity & Resp Medicine, The University of Manchester, United Kingdom
name: Dave Singh, MD
role: PRINCIPAL_INVESTIGATOR
References: