Health Condition 1: J449- Chronic obstructive pulmonary disease, unspecified
Conditions
Interventions
Intervention1: Tezepelumab 420 mg: Formulation: Injection
Dose strength: 110 mg/mL
Route: Subcutaneous
Frequency: Every 4 weeks
Intervention2: Tezepelumab 210 mg: Formulation: Injection
Dose stre
Sponsors
AstraZeneca AB
AstraZeneca Pharma India Ltd
Eligibility
Inclusion criteria
Inclusion criteria: Age 1 Adult participants 40 to 80 years of age at the time of signing the informed consent. 2 Documented physician-diagnosed COPD for at least 12 months before Visit 1. 3 A post-BD FEV1/FVC less than 0.70 and a post-BD FEV1 greater than or equal to 20% and less than or equal to 70% of the predicted normal value during screening. 4 Documented regular dose of triple (ICS+LABA+LAMA) or dual (LABA+LAMA, ICS+LABA, ICS+LAMA) inhaled therapy for at least 3 consecutive months before Visit 1. 5 Documented history reater than or equal to 2 moderate1 or reater than or equal to 1 severe2 COPD exacerbations within 12 months before Visit 1. At least 1 of the 2 moderate exacerbations must have been treated with SCS. 6 EOS greater than or equal to 150 cells per microliter during the screening period. 7 CAT total score reater than or equal to 15 at Visit 1. 8 Current or former smokers (with smoking cessation reater than or equal to 6 months before Visit 1) have a history of at least 10 pack-years of tobacco smoking (1 pack year = 20 cigarettes smoked per day for 1 year). 9 Body weight reater than or equal to 40 kg at Visit 1. 10 Participants not of childbearing potential are defined as participants who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to the planned date of randomisation without an alternative medical cause. The following age-specific requirements apply - Women less than 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and FSH levels in the postmenopausal range. - Women reater than or equal to 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment PoCBP must use one highly effective form of birth control. A highly effective method of contraception is defined as one that can achieve a failure rate of company 1% per year when used consistently and correctly. PoCBP who are sexually active with a non- sterilised partner must agree to use one highly effective method of birth control as definedbelow, from screening throughout the study and until at least 16 weeks after the final dose of IP. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method are not acceptable methods of contraception. Female condom and male condom should not be used together. - Highly effective birth control methods include: Total sexual abstinence is an acceptable method provided it is the usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments) [(periodic abstinence eg, calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to study intervention, and withdrawal are not acceptable methods of contracepti
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1. Clinically important pulmonary disease other than COPD (eg, active lung infection, clinically significant bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency and primary ciliary dyskinesia) or another diagnosed pulmonary or systemic disease that is associated with elevated peripheral EOS (eg, allergic bronchopulmonary aspergillosis/mycosis, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome). 2. Radiological findings suggestive of a respiratory disease other than COPD that is significantly contributing to the participant s respiratory symptoms. Radiological findings of pulmonary nodules suspicious for lung cancer, as per applicable guidance, (eg, ACR Lung-RADS v2022, (Christensen et al 2024)) without appropriate follow up before Visit 2. 3. Radiological findings suggestive of acute infection. 4. Current physician diagnosed asthma according to the Global Initiative for Asthma (GINA 2024 and onwards versions) guidelines or other accepted guidelines, past physician diagnosed asthma including paediatric asthma, or asthma-COPD overlap syndrome. 5. Any unstable disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, immune, psychiatric, or major physical/or cognitive impairment that is not stable in the opinion of the investigator or the sponsor and/or could: a. Affect the safety of the participant throughout the study b. Influence the findings of the study or their interpretation c. Impede the participant s ability to complete the entire duration of the study and/or comply with the study visit schedule and procedures. 6. Unstable cardiovascular disorder (including but not limited to ischemic heart disease, arrhythmia, cardiomyopathy, severe right and/or left heart failure (NYHA class IV)), renal failure, uncontrolled hypertension, as defined by the Investigator, or any other relevant cardiovascular disorder or ECG abnormality that in the Investigator s judgment may put the participant at risk or negatively affect the outcome of the study. 7. Acute upper or lower respiratory infection requiring antibiotics or systemic antiviral medication within 2 weeks before Visit 1 (based on the last day of antibiotic/antiviral treatment, whichever occurred later). Lower respiratory infection requiring hospitalisation less than 4 weeks before Visit 1 (based on the date of discharge from hospital). 8. COPD exacerbation treated with SCS and/or antibiotics within 2 weeks before Visit 1 (based on the last dose of corticosteroids or antibiotics, whichever occurred later), or/and requiring hospitalisation for COPD within 4 weeks before Visit 1 (based on the date of discharge from hospital). 9. A helminth parasitic infection within 6 months before Visit 1 that has not been treated with, or has failed to respond to, the SoC therapy, or diagnosed during the screening period. 10. Immunodeficiency disorder including a positive HIV test before Visit 1 or during the screening period. 11. Tuberculosis requiring treatment within the 12 months before Visit 2. 12. Anaphylaxis or documented immune complex disease (T
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare the effect of tezepelumab with placebo on moderate or severe COPD exacerbations in participants with moderate to very severe COPDTimepoint: Annualised rate of moderate or severe COPD exacerbations up to 76 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| To compare the effect of tezepelumab with placebo on pre-BD lung function in participants with moderate to very severe COPDTimepoint: Change from baseline in pre-BD FEV1 at Week 52;To compare the effect of tezepelumab with placebo on HRQL in participants with moderate to very severe COPDTimepoint: Change from baseline in the SGRQ total score over 52 weeks;To compare the effect of tezepelumab with placebo on moderate or severe COPD exacerbations in participants with moderate to very severe COPD and screening EOS greater than or equal to 300 cells per microliteTimepoint: Annualised rate of moderate or severe COPD exacerbations up to 76 weeks among participants with screening EOS greater than or equal to 300 cells per microlite;To compare the effect of tezepelumab with placebo on severe COPD exacerbationTimepoint: Annualised rate of severe COPD exacerbations up to 76 weeks;To compare the effect of tezepelumab with placebo on HRQLin participants with moderate to very severe COPDTimepoint: Participants achieving a clinically meaningful improvement from baseline in SGRQ total score (4-point score decrease over) 52 weeks ;To compare the effect of tezepelumab with placebo on COPD health status in participants with moderate to very severe COPDTimepoint: Change from baseline in the CAT total score over 52 weeks Participants achieving a clinically meaningful improvement from baseline in CAT total score (2-point score decrease) over 52 weeks ;To compare the effect of tezepelumab with placebo on time to first moderate to severe COPD exacerbationTimepoint: Time to first moderate to severe COPD exacerbation up to 76 weeks;To compare the effect of tezepelumab with placebo on time to first severe COPD exacerbationTimepoint: Time to first severe COPD exacerbation up to 76 weeks;To explore the effect of tezepelumab on post-BD lung functionTimepoint: Change from baseline in post-BD FEV1 at Week 52;To assess the PK and immunogenicity of tezepelumab in participants with moderate to | — |
Countries
Brazil, Canada, Chile, China, Czech Republic, Denmark, Germany, India, Italy, Malaysia, Mexico, Philippines, Poland, Republic of Korea, Slovakia, Spain, United Kingdom, United States of America
Contacts
Public ContactTapankumar M Shah
AstraZeneca Pharma India Ltd.
Outcome results
None listed