Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With a History of Frequent Exacerbations

Korábbi kezelés

• 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 the age of 18.
• Long-term treatment with oxygen >4.0 L/min and/or oxyhemoglobin saturation <89% while breathing supplemental oxygen.
• Helminth parasitic infection within 24 weeks prior to enrollment, not treated or failed to respond to standard of care therapy.
• Alcohol or drug abuse within the past year, which may compromise the study data.
• 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.
• 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).
• Scheduled major surgical procedure during the study. Minor elective procedures are allowed.
• Receipt of blood products or immunoglobulins within 30 days prior to randomization.
• 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.
• Receipt of live attenuated vaccines 30 days prior to randomization.
• Chronic use of immunosuppressive medication or expected need for chronic use during the study.
• Chronic use of antibiotics if duration of treatment is <9 months prior to randomization. Chronic macrolide or other antibiotic therapy is allowed provided the patient has been on stable dose/regimen for ≥9 months prior to randomization and has had ≥2 COPD exacerbations while on stable therapy.
• Receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to enrollment.
• Receipt of benralizumab within 12 months prior to enrollment.

Más betegség

• Clinically important pulmonary disease other than COPD
• 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.
• Any unstable disorder that could affect patient safety, study findings or the patient's ability to complete the study.
• Cor pulmonale and/or right ventricular failure.
• Use of any non-invasive positive pressure ventilation device (NIPPV). Note: use of CPAP for Sleep Apnea Syndrome is allowed.
• Known immunodeficiency disorder, including positive HIV-1/2 testing.
• 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.
• 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.
• History of anaphylaxis to any biologic therapy or vaccine.
• Known history of allergy or reaction to any component of the IP formulation.

Laborértékek

• Another pulmonary or systemic disease associated with elevated peripheral eosinophil counts.
• 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.
• ALT or AST ≥3 times the upper limit of normal, confirmed by repeated testing during the run-in period.

Egyéb

• Participation, or planned participation, in intensive COPD rehabilitation program (maintenance phase of a rehabilitation is allowed).

• Provision of informed consent
• Age 40 to 85 years
• Male and/or female.
• Current or former smoker with a tobacco history of ≥10 pack-years.
• History of moderate to very severe COPD with a post-bronchodilator FEV1/FVC<0.70 and FEV1 ≤65% of predicted normal value.
• Documented history of 2 or more COPD exacerbations that required treatment with systemic corticosteroids and/or hospitalization within 52 weeks prior to enrollment.
  • Exacerbations treated with antibiotics alone are excluded unless accompanied by treatment with systemic corticosteroids and/or hospitalization.
  • Hospitalization is defined as an inpatient admission ≥24 hours
  • Previous exacerbations should be confirmed to have occurred while on stable triple therapy for COPD.
  • At least one qualifying COPD exacerbation should occur while on stable uninterrupted triple therapy prior to enrolment.
• Documented use of triple (ICS/LABA/LAMA) background therapy for COPD for ≥3 months immediately prior to enrollment.
  • 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.
  • ICS in a dose approved for COPD or equivalent to ≥250 mcg of fluticasone propionate daily.
  • Total cumulative duration of not being on double or triple background therapy must not exceed 2 months.
  • Stable therapy/doses for the last 3 months prior to randomization.
• 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).
• CAT total score ≥15 at Visit 1.
• Negative pregnancy test for females of childbearing potential (WOCBP) at Visit 1.
• 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).