Efficacy and Safety Study of Benralizumab in patients With Uncontrolled Asthma on Medium to High Dose Inhaled Corticosteroid Plus LABA

• Register: EUCTR
• Last refreshed on: 17 July 2017
• Main ID: EUCTR2017-000702-38-Outside-EU/EEA
• Date of registration: 06/07/2017
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: Efficacy and Safety Study of Benralizumab in patients With Uncontrolled Asthma on Medium to High Dose Inhaled Corticosteroid Plus LABA
• Scientific title: A Multicentre, Randomised, Double-blind, Parallel Group, Placebocontrolled, Phase 3 Efficacy and Safety Study of Benralizumab (MEDI-563) Added to Medium to High-dose Inhaled Corticosteroid Plus Long-acting ß2 Agonist in Patients with Uncontrolled Asthma - MIRACLE
• Target sample size: 834
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000702-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

China, Korea, Republic of, Philippines, Taiwan

Contacts

• Name: Information Center
• Affiliation: AstraZeneca AB

• Name: Information Center
• Affiliation: AstraZeneca AB

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion Criteria:

• Written informed consent, and assent when applicable 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.

• Female and male aged 12 to 75 years, inclusively, at the time of Visit 1. For those patients, who are 17 on the day of Visit 1 but will turn 18 after this day, will be considered an adolescent for the purposes of this trial.

• History of physician-diagnosed asthma requiring treatment with medium-to-high dose ICS (>250µg fluticasone dry powder formulation equivalents total daily dose) and a LABA, for at least 6 months prior to Visit 1.

• Additional maintenance asthma controller medications that are locally approved in a country for the treatment of asthma (eg, LTRAs, tiotropium, cromone, theophylline, oral corticosteroid), and have been used for at least 30 days prior to Visit 1 are allowed.

• At least 2 documented asthma exacerbations in the 12 months prior to the date informed consent, and assent, at least 1 of the 2 exacerbations should occur during the treatment of medium-to-high dose ICS-LABA, when applicable is obtained that required use of a systemic corticosteroid or a temporary increase from the patient’s usual maintenance dose of oral corticosteroid. For patients who are re-screened within 30 days of their screen failure date, the calculation of the 12 month period should be done from the original informed consent, and assent when applicable date.

• Documented post-bronchodilator (post-BD) reversibility in FEV1 of =12% and = 200 mL in FEV1 within 12 months prior to Visit 1. If historical documentation is not available, reversibility must be demonstrated and documented at Visit 2.

• Fulfilment of at least 1 of the following conditions over the 7 days prior to randomization:
- >2 days with a daytime or night time symptoms score >1
- Rescue SABA use on >2 days
- =1 nocturnal awakening due to asthma
Are the trial subjects under 18? yes
Number of subjects for this age range: 36
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 756
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 42

Exclusion criteria:
Exclusion Criteria:

• Clinically important pulmonary disease other than asthma (eg, active lung infection, COPD, 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).

• 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.

• Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date informed consent, and assent when applicable, is obtained or during the screening period.

• 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 entire duration of the study.

• Current smokers or former smokers with a smoking history of > 10 pack-years.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Asthma
MedDRA version: 20.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Product Name: Benralizumab
Product Code: MEDI-563
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Benralizumab
CAS Number: 1044511-01-4
Current Sponsor code: MEDI-563
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: To evaluate the effect of benralizumab on asthma exacerbations in patients on medium to high-dose ICS-LABA with uncontrolled asthma.

Secondary Objective: • To assess the effect of benralizumab on pulmonary function

• To assess the effect of benralizumab on asthma symptoms and other asthma control metrics

• To assess the effect of benralizumab on other parameters associated with asthma exacerbations

• To assess the effect of benralizumab on health-related quality of life

• To assess the effect of benralizumab on emergency room/urgent care visits and hospitalizations due to asthma

• To evaluate the effect of benralizumab on health care resource utilization

• To evaluate the pharmacokinetics and immunogenicity of benralizumab

•To assess the impact of benralizumab on blood eosinophil levels

Timepoint(s) of evaluation of this end point: 48 weeks

Primary end point(s): Annual asthma exacerbation rate, which will be analysed in patients with baseline blood eosinophil counts = 300/µL

Secondary Outcome(s)

Secondary end point(s): All the below secondary efficacy endpoints will be analysed in patients with baseline blood eosinophil counts = 300/µL:

• Pre-bronchodilator FEV1

• Asthma symptom score (total, daytime,and night time), rescue medication use, home lung function (morning and evening PEF), nights with awakening due to asthma, Asthma Control Questionnaire 6 (ACQ-6)

• Time to first asthma exacerbation and proportion of patients with=1 asthma exacerbation

• St. George’s Respiratory Questionnaire (SGRQ)

• Annual rate of asthma exacerbations that are associated with an emergency room/urgent care visit or a hospitalization

• Asthma specific resource utilization (eg, unscheduled physician visits, use of other asthma medications)

• PK parameters and Anti-drug antibodies

• Blood eosinophils

Timepoint(s) of evaluation of this end point: 48 weeks

Secondary ID(s)

D3250C00036

NCT03186209

Source(s) of Monetary Support

AstraZeneca AB