Efficacy and Safety of Benralizumab in Moderate to Very Severe ChronicObstructive Pulmonary Disease (COPD) with a History of Frequent Exacerbations

Phase 1

• Conditions: Chronic Obstructive Pulmonary Disease; MedDRA version: 21.1Level: PTClassification code 10009033Term: Chronic obstructive pulmonary diseaseSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2019-001800-39-PL
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-07-26
• Last Update Posted: 26 February 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 642

Inclusion Criteria

1 Provision of informed consent
2 Age 40 to 85 years
3 Male and/or female.
4 Current or former smoker with a tobacco history of =10 packyears.
5 History of moderate to very severe COPD with a postbronchodilator
FEV1/FVC<0.70 and FEV1 =65% of predicted normal
value.
6 Documented history of 2 or more COPD exacerbations that
required treatment with systemic corticosteroids and/or hospitalization
within 52 weeks prior to enrollment.
(a) Exacerbations treated with antibiotics alone are excluded unless
accompanied by treatment with systemic corticosteroids and/or
hospitalization.
(b) Hospitalization is defined as an inpatient admission =24 hours
(c) Previous exacerbations should be confirmed to have occurred while
on stable triple therapy for COPD.
(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/LAMA) background therapy for
COPD for =3 months immediately prior to enrollment.
(a) Treatment with at least double inhaled therapy containing ICS 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
(c) Total cumulative duration of not being on double or triple
background therapy must not exceed 2 months.
(d) Stable therapy/doses for the last 3 months prior to randomization.
8 Blood eosinophil count =300/µL at screening and documented
historical eosinophil count of =150/µL within 52 weeks of enrollment (or
repeated testing during run-in).
9 CAT total score =15 at Visit 1.
10 Negative pregnancy test for females of childbearing potential
(WOCBP) at Visit 1.
11 Women of childbearing potential (WOCBP) must agree to use a
highly effective method of birth control from enrollment throughout the
study and within 12 weeks after last dose of IP.
Women not of childbearing potential are defined as women who are
either permanently sterilized or postmenopausal (confirmed by FSH test
for women <50 years).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 321
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 321

Exclusion Criteria

1 Clinically important pulmonary disease other than COPD
2 Current diagnosis of asthma, prior history of asthma or asthma-
COPD overlap according to GINA/GOLD. Childhood history of asthma is
allowed and defined as asthma diagnosed and resolved before theage of
18.
3 Radiological findings of a respiratory disease other than COPD
contributing to respiratory symptoms. Solitary pulmonary nodules
without appropriate follow up or findings of acute infection.
4 Another pulmonary or systemic disease associated with
elevated peripheral eosinophil counts.
5 Any unstable disorder that could affect patient safety, study
findings or the patient's ability to complete the study.
6 Any clinically significant abnormal findings in physical
examination, vital signs, ECG, laboratory tests could affect patient
safety, study findings or the patient's ability to complete the study.
7 Cor pulmonale and/or right ventricular failure.
8 Long-term treatment with oxygen >4.0 L/min and/or
oxyhemoglobin saturation <89% while breathing supplemental oxygen.
9 Use of any non-invasive positive pressure ventilation device
(NIPPV). Note: use of CPAP for Sleep Apnea Syndrome is allowed.
10 Known immunodeficiency disorder, including positive HIV-1/2
testing.
11 Active liver disease. Chronic stable hepatitis B and C (including
positive HBsAg or hepatitis C antibody testing), or other stable chronic
liver disease are acceptable.
12 ALT or AST =3 times the upper limit of normal, confirmed by
repeated testing during the run-in period.
13 Helminth parasitic infection within 24 weeks prior to
enrollment, not treated or failed to respond to standard of care therapy.
14 Alcohol or drug abuse within the past year, which may
compromise the study data.
15 Malignancy, current or within the past 5 years, except for
adequately treated non invasive basal cell and squamous cell carcinoma
of the skin and cervical carcinoma-in-situ treated with apparent success
more than 1 year prior to Visit 1. Suspected malignancy or undefined
neoplasms.
16 Evidence of active tuberculosis, as judged by investigator. Patients with a recent (within 2 years) first-time or newly positive PPD or Quantiferon test need to complete an appropriate course of treatment before enrollment. Evaluation will be according to the local standard of care.
17 Participation, or planned participation, in intensive COPD rehabilitation program (maintenance phase of a rehabilitation is allowed).
18 History of surgical or endoscopic lung volume reduction within the 6 months prior to enrollment. History of partial or total lung resection (single lobe or segmentectomy is acceptable).
19 Scheduled major surgical procedure during the study. Minor elective procedures are allowed.
20 History of anaphylaxis to any biologic therapy or vaccine.
21 Receipt of blood products or immunoglobulins within 30 days prior to randomization.
22 Receipt of marketed or investigational biologic product within 4 months or 5 half-lives prior to randomization, whichever is longer. Exception: Patients on stable therapy for 3 months before randomization who intend to stay on treatment throughout the study with marketed biologic products that are not likely to interfere with the safety assessment and/or efficacy of benralizumab, for example, for the treatment of osteoporosis, migraine, pain, diabetes, obesity, ocular, cardiovascular, or metabolic diseases, can participate in the study.
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Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified