E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Asthma (an illness that causes breathing difficulty) that is not fully controlled, so that episodes of breathing difficulty are still occuring despite the use of other available treatments |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the safety and tolerability of two dosing regimens of benralizumab for adult and adolescent patients. |
|
E.2.2 | Secondary objectives of the trial |
1.To evaluate the effect of two dosing regimens of benralizumab on asthma exacerbations.
2.To evaluate the effect of two dosing regimens of benralizumab on health care utilization and work and productivity loss.
3.To assess the effect of two dosing regimens of benralizumab on asthma related and general health-related quality of life. 4.To assess the effect two dosing regimens of benralizumab on asthma control.
5.To evaluate the pharmacokinetics and immunogenicity of two dosing regimens of benralizumab.
6.To assess the effect of two dosing regimens of benralizumab on pulmonary function.
7.To assess the impact of two dosing regimens of benralizumab on blood eosinophil levels. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Informed consent (and/or assent as applicable locally) for study
participation must be obtained prior to any study related procedures being
performed (local regulations are to be followed in determining the
assent/consent requirements for children and parent(s)/guardian(s)) and
according to international guidelines and/or applicable European Union
guidelines. Patients that enter this study as an adolescent (at Visit 1) will be
re-consented using the appropriate ICF at the study visit following their 18th
birthday, prior to any study procedures being performed.
2. Female and male patients who completed the double-blind treatment
period in a predecessor study on benralizumab or matching placebo.
3. Women of childbearing potential (WOCBP) must agree to use an
effective form of birth control throughout the study duration and for 16
weeks after the last dose of Invesigational Product (IP).
4. For WOCBP only: Have a negative urine pregnancy test prior to
administration of IP at Visit 1.
5. All male patients who are sexually active must agree to use a double
barrier method of contraception from the first dose of IP until 16 weeks
after their last dose. |
|
E.4 | Principal exclusion criteria |
1.Any disorder including but not limited to cardiovascular, gastrointestinal,
hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic,
haematological, 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 studies or their
interpretations-Impede the patient’s ability to complete the entire duration of
study 2.A helminth parasitic infection diagnosed during a predecessor study
that has either not been treated, has been incompletely treated or has failed
to respond to standard of care therapy 3.Any clinically significant change in
physical examination, vital signs, electrocardiogram (ECG), haematology,
clinical chemistry, or urinalysis during a predecessor study 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
interfere with the patient’s ability to complete the entire duration of the study
4.Current malignancy or malignancy that developed during a predecessor
study (subjects that had basal cell carcinoma, localized squamous cell
carcinoma of the skin which was resected for cure, or in situ carcinoma of the
cervix that has been treated/cured will not be excluded). 5. Patients with
major protocol deviations in any of the predecessor studies at the discretion of
the Sponsor |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Number of Adverse Events/Serious Adverse Events (AEs/SAEs)• Laboratory
variables• Electrocardiogram (ECG)• Physical Examination |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
56 weeks in adult patients
108 weeks in adolescent patients
Data from adult patients choosing to enter the safety extension study,
D3250C00037, will be summarized separately from those remaining in
this study (Bora), unless otherwise noted in the SAP.
Those patients will stay in BORA for at least 16 weeks and no more than
40 weeks. |
|
E.5.2 | Secondary end point(s) |
• Annual asthma exacerbation rate, where an asthma exacerbation is defined
by a worsening of asthma requiring the use of systemic corticosteroids for at least 3 days, and/or an in patient hospitalization, and/or an emergency
department or urgent care visit• Work Productivity and Activity Impairment
Questionnaire plus Classroom Impairment Questions (WPAI+CIQ)•
Hospitalizations, Emergency Department (ED) visits, urgent care visits and all
other outpatient visits due to asthma• Standardised Asthma Quality of Life
Questionnaire for 12 Years and Older (AQLQ(S)+12)• European Quality of
Life-5 Dimensions (EQ-5D-5L) questionnaire• Asthma Control Questionnaire 6
(ACQ-6)• Pharmacokinetic (PK) parameters• Anti-drug antibodies (ADA)• Prebronchodilator
Forced expiratory volume in 1 second (FEV1) and postbronchodilator
FEV1 at the study centre• Blood eosinophils |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
56 weeks in adult patients
108 weeks in adolescent patients
Data from adult patients choosing to enter the safety extension study,
D3250C00037, will be summarized separately from those remaining in
this study (Bora), unless otherwise noted in the SAP.
Those patients will stay in BORA for at least 16 weeks and no more than
40 weeks. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Open study for EU adolescents |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 160 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Brazil |
Bulgaria |
Canada |
Chile |
Czech Republic |
France |
Germany |
Italy |
Japan |
Korea, Republic of |
Mexico |
Peru |
Philippines |
Poland |
Romania |
Russian Federation |
South Africa |
Spain |
Sweden |
Turkey |
Ukraine |
United Kingdom |
United States |
Vietnam |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |