Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, Moderate COPD, Severe COPD, Very Severe COPD, chronic obstructive pulmonary disease
Brief summary
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Adults with Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD)
Detailed description
This is a Phase 3, 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 inhaled maintenance therapy and having had at least 2 moderate, or 1 severe, COPD exacerbations in the 12 months prior to Visit 1. Subjects will receive monthly subcutaneous injection of one of two different doses of tezepelumab, or placebo, with a maximum treatment duration of 76 weeks and a minimum of 52 weeks. The study also includes a off-treatment safety follow-up period of 12 weeks.
Interventions
BIOLOGICALTezepelumab
Tezepelumab subcutaneous injection
OTHERPlacebo
Placebo subcutaneous injection
Sponsors
AstraZeneca
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blinded
Intervention model description
Participants will be randomised in a ratio of 1:1:1 to receive Dose 1 of tezepelumab, Dose 2 of tezepelumab or matching placebo.
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. ≥40 to ≤80 years old 2. COPD diagnosis ≥1 year, 3. Post-BD FEV1 ≥ 20% and ≤ 70% PN, FEV1/FVC \<0.70 at screening 4. Triple (ICS+LABA+LAMA) or dual inhaled COPD therapy, if triple therapy is considered not appropriate, ≥3 consecutive months prior to V1 5. ≥2 moderate or ≥1 severe COPD exacerbations in the prior year; At least 1 of 2 moderate exacerbations must require the use of systemic corticosteroids. At least one of the previous exacerbations should be confirmed to have occurred while the participant was on triple or dual inhaled maintenance therapy 6. EOS ≥ 150 cells/μL during screening 7. CAT ≥15 at screening 8. Former or current smokers ≥10 pack-years
Exclusion criteria
1. Clin. important pulmonary disease or radiological findings suggestive of a respiratory disease other than COPD 2. Asthma, incl. pediatric, or ACOS 3. Any unstable disorder that can impact participants safety or study outcomes 4. Tuberculosis requiring treatment within 12 months prior V2 5. Malignancies current or past Concomitant therapies: * Macrolides (less than 6 months) * Systemic immuno-suppressive, -modulating medications 6. LTOT \>4.0 L/min or O2 saturation \<89% despite LTOT
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualised rate of moderate or severe COPD exacerbations | Baseline up to 76 weeks | The annualised moderate or severe COPD exacerbation rate (based on exacerbations reported by the investigator) up to 76 weeks treatment period compared to placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in post-BD FEV1 | From baseline to Week 52 | Change from baseline in post-BD FEV1 at Week 52 compared to placebo. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration |
| Change from baseline in pre-dose/pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) | From baseline to Week 52 | Change from baseline in pre-BD FEV1 at Week 52 compared to placebo. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration |
| Change from baseline in the St. George's Respiratory Questionnaire (SGRQ) total score | From baseline over 52 weeks | Change from baseline in the SGRQ total score over 52 weeks compared to placebo. SGRQ is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with lower scores indicating better health status. |
| Annualised rate of moderate or severe COPD exacerbations among participants with EOS ≥ 300 cells/µL collected during screening visit. | Baseline up to 76 weeks | The annualised moderate or severe COPD exacerbation rate (based on exacerbations reported by the investigator) up to 76 weeks treatment period compared to placebo among participants with EOS ≥ 300 cells/µL collected during screening visit. |
| Annualised rate of severe COPD exacerbations | Baseline up to 76 weeks | The annualised severe COPD exacerbation rate (based on exacerbations reported by the investigator) up to 76 weeks treatment period compared to placebo |
| Annualised rate of COPD exacerbations requiring ER visit and/or hospitalisation | Baseline up to 76 Weeks | The annualised rate of COPD exacerbation requiring ER visit and/or hospitalisation up to 76 weeks treatment period compared to placebo. |
| Clinical meaningful improvement in St. George's Respiratory Questionnaire (SGRQ) total score | From baseline over 52 weeks | Participants achieving a clinically meaningful improvement from baseline in SGRQ total score (4-point score decrease) over 52 weeks. SGRQ is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with lower scores indicating better health status. |
| Change from baseline in the COPD assessment Test (CAT) total score | From baseline over 52 weeks | Change from baseline in the CAT total score over 52 weeks CAT is an 8-item PRO that measures the impact of COPD on the health status of patients with COPD. The CAT has a scoring range of 0-40 with higher scores indicative of greater COPD impact on health status. |
| Clinical meaningful improvement in COPD Assessment Test (CAT) total score | From baseline over 52 weeks | Participants achieving a clinically meaningful improvement from baseline in CAT total score (2-point score decrease) over 52 weeks. CAT is an 8-item PRO that measures the impact of COPD on the health status of patients with COPD. The CAT has a scoring range of 0-40 with higher scores indicative of greater COPD impact on health status. |
| Time to first moderate or severe COPD exacerbation | Baseline up to 76 weeks | Time to first occurrence of moderate or severe COPD exacerbation up to 76 weeks |
| Time to first severe COPD exacerbation | Baseline up to 76 weeks | Time to first occurrence of severe COPD exacerbation up to 76 weeks |
| Pharmacokinetics (PK): Serum trough concentrations | Baseline, Week 24, Week 36, Week 52 | Serum trough concentrations |
| Immunogenicity of anti-drug antibodies (ADA) | Baseline, Week 24, Week 36, Week 52 | Incidence of anti-drug antibodies |
Countries
Argentina, Australia, Belgium, Bulgaria, Colombia, Denmark, France, Greece, Hong Kong, Hungary, Israel, Japan, Netherlands, New Zealand, Peru, Romania, South Africa, Sweden, Thailand, Turkey (Türkiye), United States, Vietnam
Contacts
CONTACTAstraZeneca Clinical Study Information Center
PRINCIPAL_INVESTIGATORMeiLan Han, MD
University of Michigan Health, Pulmonary & Critical Care Medicine,
Outcome results
None listed