Severe Eosinophilic Asthma MedDRA version: 21.1 Level: LLT Classification code 10068462 Term: Eosinophilic asthma System Organ Class: 100000004855
Conditions
Interventions
Product Name: Benralizumab
Product Code: MEDI-563
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Benralizumab
CAS Number: 1044511-01-4
Current Sponsor code: MEDI-563
Other descriptiv
Sponsors
AstraZenenca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Parent(s)/guardian are able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. If applicable, the participant must be able and willing to give assent to take part in the study according to the local requirement. 2.Patient must be 6 to 11 years of age inclusive (6 to 14 years of age inclusive in Japan), at the time of signing the ICF. 3.Diagnosis of severe asthma, defined by the regional guidelines (ie, National Institutes of Health [NIH], Global Initiative for Asthma [GINA], American Thoracic Society [ATS], European Respiratory Society [ERS], Japanese Society of Pediatric Allergy and Clinical Immunology [JSPACI], etc.), for at least 12 months prior to Visit 1. If the patient is naïve to the study site, the participant/guardian must self-report a physician diagnosis of asthma and the investigator must confirm by review of medical history with the participant/guardian. 4.A previously confirmed history of two or more exacerbations requiring treatment with systemic corticosteroids* and/or hospitalization in the 12 months prior to Visit 1, despite the use of ICS, or a persistent need for oral corticosteroid maintenance treatment to maintain asthma control, for at least 3 of the last 12 months prior to Visit 1, despite the use of ICS. *For patients receiving maintenance oral corticosteroids, the OCS treatment for the exacerbations must have been a two-fold increase or greater in the dose. 5.Eosinophilic airway inflammation that is related to asthma characterized as eosinophilic in nature as indicated by peripheral blood eosinophil count of =150 cells / µL at Visit 1. 6.A well-documented requirement for regular treatment with ICS: total daily dose equivalent to =250 µg fluticasone propionate, or =400 µg budesonide (=320 µg budesonide ex-actuator), or =200 µg fluticasone furoate, or =220 µg mometasone furoate, or =160 µg ciclesonide, or =1000 µg triamcinolone acetonide, or =500 µg beclomethasone dipropionate, or =200 µg beclomethasone dipropionate (HFA) in the 12 months prior to Visit 1, with or without maintenance oral corticosteroids. Medium dose ICS as per local guidelines will also satisfy the inclusion criterion after agreement with the Study Physician. 7.Current treatment with at least 1 additional controller medication, such as inhaled LABA, leukotriene receptor antagonist, long acting anti-muscarinic agent, or theophylline, since at least 3 months prior to Visit 1. 8.Forced expiratory volume in 1 second (FEV1): Flow/ volume curve indicating airflow obstruction at either Visit 1 or 2 (performed prior to first dose of study medication), associated with: a pre-bronchodilator FEV1 = 110% predicted normal, or, FEV1/Forced Vital Capacity ratio = 0.8. 9.Body weight =15 kg. 10.Male or female 11.Females of childbearing potential (FOCBP) who are sexually active, as judged by the investigator, must commit to consistent and correct use of an acceptable method of contraception for the duration of the study and for 4 months after the last dose of IP. Are the trial subjects under 18? yes Number of subjects for this age range: 33 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Any history of life-threatening asthma (eg, requiring intubation) 2.Clinically important pulmonary disease other than asthma such as active lung infection, bronchiectasis, pulmonary fibrosis, cystic fibrosis, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia 3.Previous diagnosis of pulmonary or systematic disease, other than asthma, that is associated with elevated peripheral eosinophil counts such as allergic bronchopulmonary aspergillosis/mycosis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), and hypereosinophilic syndrome 4.Ever been diagnosed with malignant disease 5.Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, immunological, psychiatric, or major physical impairment that is not stable in the opinion of the investigator and could:Affect the safety of the patient throughout the study, Influence the findings of the study or their interpretations, Impede the patient’s ability to complete the entire duration of the study 6.History of anaphylaxis to any biologic therapy 7.Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening 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 8.Any clinically significant cardiac disease or any electrocardiogram (ECG) abnormality obtained during the screening period, which in the opinion of the investigator may put the patient at risk or interfere with study assessments 9.Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a positive medical history for hepatitis B or C. Patients with a history of hepatitis B vaccination without history of hepatitis B are allowed to enrol 10.A helminth parasitic infection diagnosed within 24 weeks prior to the date of informed consent and assent is obtained that has not been treated with, or has failed to respond to, standard of care therapy 11.Alanine aminotransferase or aspartate aminotransferase level =1.5 times the upper limit of normal confirmed during the screening period 12.A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test 13.Use of immunosuppressive medication, including, but not limited to, methotrexate, troleandomycin, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid, or any experimental anti-inflammatory therapy, within 3 months prior to Visit 1. Chronic maintenance corticosteroid for the treatment of asthma is allowe. 14.Receipt of immunoglobulin or blood products within 30 days prior to Visit 1 15.Receipt of any marketed (eg, omalizumab, mepolizumab, or off-label benralizumab) or investigational biologic within 4 months or 5 half-lives, whichever is longer, prior to Visit . 16.Receipt of live attenuated vaccines 30 days prior to the date of first dose of IP 17.Initiation of new allergen immunotherapy is not allowed within 30 days prior to Visit 1.However, allergen immunotherapy initiated prior to this period can be continued provided there is a gap of 7 days between the immunotherapy and IP administration. 18.Current use of any oral or ophthalmic non-selective ß-adrenergic antagonist (eg, propranolol) 19.Planned surgical procedures during the conduct of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -To evaluate the pharmacokinetics (PK) of benralizumab administered subcutaneously (SC) in children from 6 to 11 years of age with severe eosinophilic asthma -To evaluate the pharmacodynamics (PD) of benralizumab administered SC in children from 6 to 11 years of age with severe eosinophilic asthma;Secondary Objective: Secondary objectives: -To characterize the PK of benralizumab -To evaluate the immunogenicity of benralizumab -To evaluate the effect of benralizumab on pulmonary function -To assess the effect of benralizumab on asthma symptoms and other asthma control metrics Safety objective: -To assess the safety and tolerability of benralizumab;Primary end point(s): 1.To evaluate pharmacokinetics of benralizumab administered subcutaneously in children from 6-11 year of age with severe eosinophilic asthma: •Clearance •Area under concentration time curve to Day 28 (AUC0-28) •Maximum serum concentration (Cmax) •Terminal phase elimination half-life (t1/2) •Time to reach Cmax (Tmax) 2.To evaluate pharmacodynamics of benralizumab administered subcutaneously in children from 6-11 year of age with severe eosinophilic asthma: •Change from baseline in peripheral blood eosinophil count;Timepoint(s) of evaluation of this end point: 1.To evaluate pharmacokinetics at visit 2(day 0), visit 3(day 1), visit 4(day 7), visit 5(day 14), visit 6(day 28), visit 7(day 56), visit 8(day 84), visit 9(day112), visit 10(day 168), visit 13(336). 2.To evaluate pharmacodynamics at visit 1(day -28 to -14), visit 6(day 28), visit 7(day 560), visit 8(day 84), visit 9(day 112), visit 10(day 168), visit 13(day 336) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Body weight-adjusted clearance -Presence of anti-benralizumab antibodies -Change from baseline in pre-dose (when applicable), pre-bronchodilator, forced expiratory volume in 1 second (FEV1) measured at Weeks 4, 8, 12, and 16 (Part A), and Weeks 24 and 48 (Part B) -Change from baseline in Interviewer-administered Asthma Control Questionnaire (ACQ-IA) score, measured at screening and Weeks 1, 2, 4, 8, 12, and 16 (Part A), and Weeks 24, 32, 40 and 48, and at follow-up (Part B) Interviewer-administered Patient Global Impression of Change (PGIC-IA), measured at Week 16 (Part A), Weeks 24, 32 and 48 (Part B), and at the DXD/WD visit Clinician Global Impression of Change (CGIC), measured at Week 16 (Part A), Weeks 24, 32 and 48 (Part B), and at the DXD/WD visit -AEs -Vital signs -Collection of clinical chemistry/haematology parameters and urinalysis;Timepoint(s) of evaluation of this end point: -Body weight-adjusted clearance at day 0,day 1,day 7,day 14,day 28,day 56,day 84,day 112,day 168,day 336 -Presence of anti-benralizumab antibodies at day 0,day 56, day 112,day 168,day 336 -Change from baseline in pre-dose, pre-bronchodilator, forced expiratory volume in 1 second at day -28 to -14,day 0,day 28,day 56,day 84,day112,day 168,day 336 -Change from baseline in Interviewer-administered Asthma Control Questionnaire score at day -28 to -14,day 0,day 7,day 14,day 28,day 56,day 84,day112,day 168,day224,day 280,day 336,day 362 - PGIC-IA and CGIC are measured at day 112,day 168,day 224,day 336 -AEs and Vital sings from day -28 to -14 to day 362 -Collection of clinical chemistry/haematology parameters and urinalysis at day -28 to -14,day 28, day 56,day 84,day112,day 168,day 336 | — |
Countries
Japan, United States
Contacts
Public ContactInformation Center
AstraZeneca AB
Outcome results
None listed