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 | 19.1 |
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 evaluate the potential effect of benralizumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult patients with severe asthma |
|
E.2.2 | Secondary objectives of the trial |
1. To further evaluate the potential effect of benralizumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult patients with severe asthma
2. To assess the potential effect of benralizumab on asthma control
3. To assess the safety and tolerability of benralizumab |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent/assent as appropriate with local guidance for study
2. Female and male patients aged 12 to 21 years, inclusively
3. Documented history of current treatment with ICS and LABA. The ICS and LABA can be parts of a combination product or given by separate inhalers. The ICS dose must be greater than or equal to 500 μg/day fluticasone propionate dry powder formulation or equivalent daily
4. Women of childbearing potential (WOCBP) must use an effective form of birth
control (confirmed by the Investigator)
5. All male patients who are sexually active must agree to use a double barrier method of
contraception (condom with spermicide) from the first dose of IP until 16 weeks after
their last dose
6. Weight of ≥40 kg
7. Evidence of asthma as documented by either:
– Airway reversibility (FEV1 ≥12% and 200 ml) demonstrated at Visit 1 or Visit 2
using the Maximum Post-bronchodilator Procedure OR
– Airway reversibility documented in the previous 12 months prior to Visit 1
8. Morning pre-bronchodilator forced expiratory volume in 1 second (FEV1) of >50%
predicted at Visit 1 or Visit 2 |
|
E.4 | Principal exclusion criteria |
1. Clinically important pulmonary disease other than asthma (eg, active lung infection,
bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts (eg, allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome)
2. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, 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
3. Any clinically significant abnormal findings in physical examination, vital signs, baseline ECG, hematology, 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 entire duration of the study
4. 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 enroll
5. Current smokers
6. History of cancer
7. Use of immunosuppressive medication (including but not limited to: oral corticosteroid [for reasons other than asthma], methotrexate, troleandomycin, cyclosporine, azathioprine, tacrolimus, mycofenolate mofetil, intramuscular longacting depot corticosteroid [for reasons other than asthma], or any experimental anti-inflammatory therapy) within 3 months prior to the date informed consent/assent
8. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent/assent is obtained
9. Receipt of any marketed (eg, omalizumab) or investigational biologic within 4 months or 5 half-lives prior to the date informed consent/assent is obtained, whichever is longer
10. Receipt of an influenza vaccine within 90 days prior to randomization
11. Previously received benralizumab (MEDI-563)
12. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.5 times the upper limit of normal (ULN) confirmed during screening period
13. Life threatening asthma defined as episodes requiring intubation associated with
hypercapnia, respiratory arrest, hypoxic seizures, or asthma related syncopal episodes |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Post-dose strain-specific hemagglutination-inhibition (HAI) antibody geometric mean fold rises
(GMFRs) from Week 8
2. Post-dose strain-specific serum HAI antibody geometric meant titers (GMTs) obtained at Week 12
3. Proportion of patients who experience a strain-specific post-dose antibody response at Week 12 with antibody response defined as a ≥4-fold rise in HAI antibody titer from Week 8
4. Proportion of patients who achieve a strain-specific post-dose HAI antibody titer ≥40 at Week 12 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. at week 8
2. at week 12
3. at week 8
4. at week 12 |
|
E.5.2 | Secondary end point(s) |
1. Proportion of patients who achieve a strainspecific post-dose HAI antibody titer ≥320 at Week 12
2. Post-dose strain-specific microneutralization (MN) antibody GMFRs from Week 8
3. Post-dose strain-specific serum MN antibody GMTs obtained at Week 12
4. Proportion of patients who experience a strainspecific post-dose antibody response at Week 12
with antibody response defined as a ≥4-fold rise in MN antibody titer from Week 8
5. Change from baseline in mean Asthma Control Questionnaire-6 (ACQ-6) score at Week 12
6. Adverse events (AEs) and serious adverse events (SAEs)
7. Laboratory variables
8. Physical Examination |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. at week 12
2. at week 8
3. at week 12
4. at week 8
5. at week 12
6. at week 0 to week 20
7. at week 0 to week 20
8. at week 0 to week 20 |
|
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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
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.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 14 |