A Study to review the Effectiveness and Safety of Benralizumab 100 mg in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) with a History of Frequent COPD Exacerbations and Elevated Peripheral Blood Eosinophils

Phase 3

• Conditions: Health Condition 1: J449- Chronic obstructive pulmonary disease, unspecified

• Registration Number: CTRI/2023/11/059825
• Lead Sponsor: AstraZeneca Pharma India Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Closed to Recruitment of Participants
• Sex: Not specified
• Target Recruitment: 0

Inclusion Criteria

Informed consent

1. Provision of signed and dated ICF prior to any mandatory study-specific procedures, sampling, and analyses.

Age and Sex

2. Patient must be 40 to 85 years of age inclusive, at the time of signing the ICF.

3. Male and/or female.

Type of patient and disease characteristics

4. Current smoker or ex-smoker with a tobacco history of =10 pack-years (1 pack-year equal to 20 cigarettes smoked per day for 1 year). (Note: electronic cigarette [e-cigarette] use does not contribute to the pack-year count for eligibility.)

5. History of moderate to very severe COPD with a post-bronchodilator FEV1/forced vital capacity (FVC) <0.70 and a post-bronchodilator FEV1 =65% of predicted normal value at screening central spirometry assessment.

6. Documented history of 2 or more moderate and/or severe COPD exacerbations12 that required treatment with systemic corticosteroids (at least 3 days or a single depot formulation injection) and/or hospitalization within 52 weeks prior to enrolment.

(a) Exacerbations treated with antibiotics alone are not considered as meeting the criterion unless it is accompanied by treatment with systemic corticosteroids and/or hospitalization.

(b) Hospitalization is defined as an inpatient admission =24 hours in the hospital, in an observation area, the emergency department, or other equivalent healthcare facility depending on the country and healthcare system.

(c) Previous exacerbations should be confirmed to have occurred while the patient was on stable double or triple (ICS/LABA/LAMA) background therapy for COPD and not as a result of a gap or step down in the treatment.

(d) At least one qualifying COPD exacerbation should occur while on stable

uninterrupted triple therapy prior to enrolment.

7. Documented use of triple (ICS/LABA/LAMA1) background therapy for COPD for =3 months immediately prior to enrollment.

(a) Treatment with at least double inhaled therapy containing ICS (e.g. ICS/LABA or ICS/LAMA) for the remaining of 52 weeks prior to enrolment. Use of LABA/LAMA is allowed if ICS cannot be tolerated.

(b) ICS in a dose approved for COPD or equivalent to =250 mcg of fluticasone propionate daily.2

(c) Patient could have switched therapies during the previous year and/or stepped down for short periods of time, although the total cumulative duration that the patient was not using inhaled double or triple background therapy must not exceed 2 months

(d) Patient must be on stable therapy/doses for the last 3 months prior to randomization. (Individual component changes or switches between devices are allowed as long as the patient remains on ICS/LABA/LAMA with an acceptable ICS dose)

8. Blood eosinophil count =300/µL at screening central laboratory testing, supported by at

least 1 documented historical blood eosinophil count of =150/µL within 52 weeks of

enrollment. In the absence of historical data, an additional blood eosinophil count must

be obtained by repeating the testing during the run-in period (at least 4 weeks apart).

9. CAT total score =15 at Visit 1 (also see inclusion criterion 15).

Reproduction

10. Negative pregnancy test (serum) for female patients of childbearing potential at Visit 1 (enrollment).

11. Women of childbearing potential (WOCBP) must agree to use a highl

Exclusion Criteria

Medical conditions

1. Clinically important pulmonary disease other than COPD (e.g. 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).

2. Current diagnosis of asthma, according to the Global Initiative for Asthma (GINA) or

other accepted guidelines, prior history of asthma, or asthma-COPD overlap according to GINA/GOLD2. Childhood history of asthma is allowed and defined as asthma diagnosed and resolved (i.e. not requiring the use of any maintenance or rescue medication) before the age of 18.

3. Radiological findings suggestive of a respiratory disease other than COPD that is

contributing to the patient s respiratory symptoms. Radiological findings of solitary

pulmonary nodules without appropriate follow up and demonstration of stability as per

standard of care or results suggestive of acute infection.

4. Another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts (e.g. allergic bronchopulmonary aspergillosis/mycosis, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome).

5. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological,

psychiatric, or major physical impairment that is not stable in the opinion of the investigator and/or could:

a.Affect the safety of the patient throughout the study

b.Influence the findings of the study or their interpretation

c.Impede the patient s ability to complete the entire duration of the study

6. Any clinically significant abnormal findings in physical examination, vital signs, ECG, hematology, clinical chemistry, or urinalysis during the run-in period, which in the opinion of the investigator may put the patient at risk because of his/her participation in the study, or may influence the results of the study, or the patient s ability to complete the entire duration of the study.

7. Signs and/or symptoms of cor pulmonale and/or right ventricular failure.

8. Patients receiving long-term treatment with oxygen >4.0 liters/minute (L/min). While breathing supplemental oxygen, patients should demonstrate an oxyhemoglobin saturation =89%. In order to be admitted to the study, patients on long-term oxygen therapy have to be ambulatory and be able to attend clinic visits.

9. Use, or need for chronic use, of any non-invasive positive pressure ventilation device (NIPPV). Note: Patients using continuous positive airway pressure (CPAP) for Sleep Apnea Syndrome are allowed in the study.

10. History of known immunodeficiency disorder including a positive test for human immunodeficiency virus, HIV-1 or HIV-2.

11. Active liver disease. Chronic stable hepatitis B and C (including positive testing for hepatitis B surface antigen or hepatitis C antibody), or other stable chronic liver disease are acceptable if patient otherwise meets eligibility criteria. Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent ja

Study & Design

• Study Type: Interventional
• Study Design: Not specified