| Eligibility |
Inclusion Criteria:
Current smoker or ex-smoker with a tobacco history of =10 pack-years (1 pack year = 20
cigarettes smoked per day for 1 year). (Note: electronic cigarette [e-cigarette] use does
not contribute to the pack-year count for eligibility).
History of moderate to very severe Chronic Obstructive Pulmonary Disease (COPD) with a
post-bronchodilator forced expiratory volume in the first second (FEV1)/forced vital
capacity (FVC) <0.70 and a post-bronchodilator FEV1 = 65% of predicted normal value at
screening central spirometry assessment.
Documented history of 2 or more moderate and/or severe COPD exacerbations in the past year
that required treatment with systemic corticosteroids (at least 3 days or a single depot
formulation injection) and/or hospitalization within 52 weeks prior to enrollment.
1. Exacerbations treated with antibiotics alone are not considered as meeting the
criterion unless it is accompanied by treatment with systemic corticosteroids and/or
hospitalization.
2. 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.
3. Previous exacerbations should be confirmed to have occurred while patient was on
stable triple Inhaled Corticosteroid (ICS)/ Long-Acting Beta2-Agonist (LABA)/
Long-Acting Muscarinic Antagonist (LAMA) background therapy for COPD and not as a
result of a step down in therapy, i.e. change from triple to dual therapy.
Documented use of triple (ICS/LABA/LAMA) background therapy for COPD throughout the year
(52 weeks) prior to enrollment.
1. ICS in a dose approved for COPD or equivalent or greater than 250 mcg of fluticasone
propionate daily.
2. 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 triple (ICS/LABA/LAMA) background therapy must not exceed 2 months.
3. 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).
For the 30 patients that will be randomized to treatment, blood eosinophil counts must be =
220 cells/µL at screening (Temple Hospital lab), supported by at least 1 documented
historical blood eosinophil count of =150 cells/microliter 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) with a result of
>=220 cells/microliter. For the 15 patients in the comparison group, blood eosinophil count
<150 cells/microliter at screening central laboratory testing. 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) with a result of <150 cells/microliter.
COPD assessment test (CAT) total score = 15 at Visit 1. Ability to read and write English.
Reproduction Negative pregnancy test (serum) for female patients of childbearing potential
at Visit 1 (enrollment).
Women of childbearing potential (WOCBP) must agree to use a highly effective method of
birth control (confirmed by the investigator) from enrollment throughout the study duration
and within 12 weeks after last dose of IP. Highly effective forms of birth control include:
- Combined (estrogen and progestogen containing) hormonal contraception associated with
inhibition of ovulation- oral, intravaginal, or transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation- oral,
injectable, or implantable
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Sexual abstinence, i.e. refraining from heterosexual intercourse (The reliability of
sexual abstinence needs to be evaluated in relation to the duration of the clinical
study and the preferred and usual lifestyle of the patient.)
- Vasectomized sexual partner (provided that partner is the sole sexual partner of the
WOCBP study patient and that the vasectomized partner has received medical assessment
of the surgical success) In addition to agreeing to use a highly effective form of
birth control, WOCBP will be counseled at each visit regarding the importance of
practicing birth control during the course of the study and not becoming pregnant.
Urine pregnancy testing will be performed and a negative pregnancy test documented at
each clinic visit.
Women not of childbearing potential are defined as women who are either permanently
sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are
postmenopausal. Women will be considered postmenopausal if the woman has been amenorrheic
for =12 months prior to the planned date of randomization without an alternative medical
cause. The following age-specific requirements apply:
- Women <50 years old will be considered postmenopausal if the woman has have been
amenorrheic for 12 months or more following cessation of exogenous hormonal treatment
and follicle stimulating hormone (FSH) levels in the postmenopausal range.
- Women =50 years old will be considered postmenopausal if the woman has been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatment.
Exclusion Criteria:
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/Global Initiative for Obstructive Lung Disease (GOLD). Childhood history of
asthma is allowed and defined as asthma diagnosed and resolved (i.e. not requiring 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 a
solitary pulmonary nodule without appropriate follow up and demonstration of stability
as per standard of care or findings suggestive of acute infection.
4. Another diagnosed pulmonary or systemic disease that is 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:
- Affect the safety of the patient throughout the study
- Influence the findings of the study or their interpretation
- Impede the patient's ability to complete the entire duration of the study
6. Signs and/or symptoms of cor pulmonale and/or right ventricular failure.
7. Patients receiving long-term oxygen treatment >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.
8. 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.
9. History of known immunodeficiency disorder including a positive test for human
immunodeficiency virus, HIV-1 or HIV-2.
10. 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 is defined by the absence of ascites, encephalopathy, coagulopathy,
hypoalbuminemia, esophageal or gastric varices, or persistent jaundice, or cirrhosis.
11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level = 3 times the
upper limit of normal (ULN), confirmed by repeated testing during the run-in period.
Transient increase of AST/ALT level that resolves by the time of randomization is
acceptable if, in the investigator's opinion, the patient does not have an active
liver disease and meets other eligibility criteria.
12. A helminth parasitic infection diagnosed within 24 weeks prior to the date informed
consent is obtained that has not been treated with, or has failed to respond to
standard of care therapy.
13. History of alcohol or drug abuse within the past year, which may compromise the study
data interpretation as judged by investigator.
14. Malignancy, current or within the past 5 years, except for adequately treated
non-invasive basal cell and squamous cell carcinoma of the skin or cervical
carcinoma-in-situ treated with apparent success more than 1 year prior to Visit 1.
Suspected malignancy or undefined neoplasms.
15. Patients who, in the opinion of the investigator or qualified designee, have evidence
of active Tuberculosis (TB). Patients with a recent (within 2 years) first-time or
newly positive purified protein derivative (PPD) test or Quantiferon test need to
complete an appropriate course of treatment before being considered for enrollment.
Evaluation will be according to the local standard of care and may consist of history
and physical examinations, chest X-ray, and/or TB test as determined by local
guidelines.
16. Patients participating in, or scheduled for, an intensive (active) COPD rehabilitation
program (patients who are in the maintenance phase of a rehabilitation program are
eligible to take part).
17. Patients with a history of surgical or endoscopic (e.g. valves) lung volume reduction
within the 6 months prior to enrollment. Patients with a history of partial or total
lung resection (single lobe or segmentectomy is acceptable).
18. Scheduled major surgical procedure during the course of the study. Minor elective
procedures are allowed.
19. History of anaphylaxis to benralizumab or any other biologic therapy.
Prior/concomitant therapy
20. Receipt of blood products or immunoglobulins within 30 days prior to randomization.
21. Receipt of any marketed or investigational biologic product for any reason within 4
months or 5 half-lives prior to randomization, whichever is longer.
22. Receipt of live attenuated vaccines 30 days prior to randomization.
23. Chronic use of immunosuppressive medication (including but not limited to:
methotrexate, troleandomycin, cyclosporine, azathioprine, rectal corticosteroids, and
systemic corticosteroids) or expected need for chronic use during the study.
24. Chronic use of antibiotics if duration of treatment is <9 months prior to
randomization (Visit 3). Chronic macrolide or other antibiotic therapy is allowed
provided the patient has been on a stable dose/regimen for = 9 months prior to
randomization and has had = 2 COPD exacerbations in the past year while on stable
therapy. If the patient was previously on chronic antibiotic but is no longer taking
it, the patient cannot be randomized until 6 weeks after the last dose.
Prior/concurrent clinical study experience
25. Receipt of any investigational non-biologic product within 30 days or 5 half-lives
prior to enrollment, whichever is longer.
26. Receipt of benralizumab within 12 months prior to enrollment.
27. Known history of allergy or reaction to any component of the intraperitoneal (IP)
formulation.
Other exclusions
28. Donation of blood, plasma, or platelets within the past 90 days prior to enrollment.
29. Pregnant, breastfeeding, or lactating women.
30. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site).
31. Judgment by the investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions, and
requirements.
Lifestyle restrictions Women of childbearing potential must use highly effective
contraceptive methods from enrollment throughout the study and for at least 12 weeks (= 5
half-lives) after last administration of the IP, as stated in inclusion criterion 11.
Patients must abstain from donating blood, plasma, or platelets from the time of informed
consent and for 12 weeks (= 5 half-lives) after last dose of IP.
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