A Multicenter, Randomized, Double-blind, Chronic-dosing, Parallel-group, Placebo-controlled Phase 3 Study to Evaluate the Efficacy 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 (RESOLUTE)
- Conditions
- Chronic Obstructive Pulmonary DiseaseCOPD10024967
- Registration Number
- NL-OMON52490
- Lead Sponsor
- Astra Zeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 15
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 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/LAMA3) 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) Total cumulative duration of not using inhaled double or being on triple
background therapy must not exceed 2 months.
(c) 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 randomization throughout the study and
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).
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 results 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 m(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 4months 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 treat
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary objective: To evaluate the effect of benralizumab 100 mg on COPD<br /><br>exacerbations in patients with moderate to very severe COPD.<br /><br>Primary endpoint: Annualized rate of moderate or severe COPD exacerbations,<br /><br>where a COPD exacerbation is defined by symptomatic worsening of COPD requiring:<br /><br>• Use of systemic corticosteroids for at least 3 days; a single depot<br /><br>injectable dose of corticosteroids will be considered equivalent to a 3-day<br /><br>course of systemic corticosteroids; and/or<br /><br>• Use of antibiotics; and/or<br /><br>• An inpatient hospitalization or death due to COPD</p><br>
- Secondary Outcome Measures
Name Time Method