Efficacy and Safety Study of Benralizumab Added to High-dose Inhaled Corticosteroid Plus LABA in Patients With Uncontrolled Asthma

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by AstraZeneca
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01928771
First received: August 16, 2013
Last updated: August 7, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to determine whether Benralizumab reduces the number of asthma exacerbations in patients who remain uncontrolled on high doses of ICS-LABA.


Condition Intervention Phase
Asthma
Biological: Benralizumab
Biological: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Multicentre, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase III Efficacy and Safety Study of Benralizumab (MEDI-563) Added to High-dose Inhaled Corticosteroid Plus Long-acting β2 Agonist in Patients With Uncontrolled Asthma

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • To evaluate the effect of 2 dosing regimens of benralizumab on asthma exacerbations in adult patients with uncontrolled asthma [ Time Frame: Immediately following the first administration of study drug through Study Week 48. ] [ Designated as safety issue: No ]
    Annual asthma exacerbation rate


Secondary Outcome Measures:
  • Assessment of the effect of 2 dosing regimens of benralizumab on pulmonary function [ Time Frame: Immediately following the first administration of study drug through Study Week 48. ] [ Designated as safety issue: No ]
    Pre-dose/pre-bronchodilator FEV1 and post-bronchodilator FEV1 at the study centre

  • Assessment of the effect of 2 dosing regimens of benralizumab on asthma symptoms and other asthma control metrics (per ePRO) [ Time Frame: Immediately following the first administration of study drug through Study Week 48. ] [ Designated as safety issue: No ]
    • Asthma symptom score (totals, day time, and night time) • Rescue medication use • Home lung function (morning and evening PEF) • Nights with awakening due to asthma • ACQ-6

  • Assessment of the effect of 2 dosing regimens of benralizumab on emergency room visits/urgent care and hospitalizations due to asthma [ Time Frame: Immediately following the first administration of study drug through Study Week 48. ] [ Designated as safety issue: No ]
    Annual rate of asthma exacerbations that are associated with an emergency room visit or a hospitalization

  • Assessment of the pharmacokinetics of benralizumab [ Time Frame: Immediately following the first administration of study drug through Study Week 48. ] [ Designated as safety issue: No ]
    PK parameters

  • Assessment of the safety and tolerability of 2 dosing regimens of benralizumab [ Time Frame: Immediately following the first administration of study drug through Study Week 48. ] [ Designated as safety issue: Yes ]
    - AE/SAE - Laboratory variables - ECG - Physical Examination

  • Assessment of the effect of 2 dosing regimens of benralizumab on other parameters associated with asthma exacerbations [ Time Frame: Immediately following the first administration of study drug through Study Week 48. ] [ Designated as safety issue: No ]
    Time to first asthma exacerbation and proportion of patients with ≥1 asthma exacerbation

  • Assessment of the immunogenicity of benralizumab [ Time Frame: Immediately following the first administration of study drug through Study Week 48. ] [ Designated as safety issue: No ]
    - Anti-drug antibodies (ADA)

  • Assessment of the effect of 2 dosing regimens of benralizumab on asthma related and general health-related quality of life [ Time Frame: Immediately following the first administration of study drug through Study Week 48. ] [ Designated as safety issue: No ]
    • AQLQ(S)+12
    • EQ-5D-5L

  • Assessment of the effect of 2 dosing regimens of benralizumab on health care resource utilization and productivity loss due to asthma [ Time Frame: Immediately following the first administration of study drug through Study Week 48 ] [ Designated as safety issue: No ]
    • WPAI+CIQ
    • Asthma specific resource utilization (eg, unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications)


Estimated Enrollment: 1890
Study Start Date: September 2013
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Benralizumab Arm A
Benralizumab administered subcutaneously.
Biological: Benralizumab
Benralizumab subcutaneously on study week 0 until study week 44 inclusive.
Experimental: Benralizumab Arm B
Benralizumab administered subcutaneously.
Biological: Benralizumab
Benralizumab subcutaneously on study week 0 until study week 44 inclusive.
Placebo Comparator: Placebo
Placebo administered subcutaneously
Biological: Placebo
Placebo subcutaneously on study week 0 until study week 44 inclusive.
Other Name: Placebo

  Eligibility

Ages Eligible for Study:   12 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent 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.
  2. 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.
  3. 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 12 months prior to Visit 1
  4. Documented treatment with ICS and LABA for at least 3 months prior to Visit 1 with or without oral corticosteroids and additional asthma controllers.

    • For subjects 18 years of age and older, the ICS dose must be >500 mcg/day fluticasone propionate dry powder formulation or equivalent daily.
    • For subjects ages 12-17, the ICS dose must be ≥500 mcg /day fluticasone propionate dry powder formulation or equivalent daily.

Exclusion criteria:

  1. Clinically important pulmonary disease other than asthma (e.g. 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 (e.g. 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, 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
  3. Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date informed consent is obtained or during the screening/run-in period
  4. Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01928771

Contacts
Contact: Clinical Trial Transparency ClinicalTrialTransparency@astrazeneca.com
Contact: AstraZeneca Clinical Study Information +1 800-236-9933 information.center@astrazeneca.com

  Show 244 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Eugene R. Bleecker, MD, Professor of Medicine Center for Genomics and Personalized Medicine Research, Medical Center Boulevard, Winston-Salem, North Carolina 27157
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01928771     History of Changes
Other Study ID Numbers: D3250C00017
Study First Received: August 16, 2013
Last Updated: August 7, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Brazil: Ministry of Health
Mexico: Ministry of Health
Peru: Ministry of Health
Australia: Department of Health and Ageing Therapeutic Goods Administration
South Korea: Korea Food and Drug Administration (KFDA)
Bulgaria: Bulgarian Drug Agency
Czech Republic: State Institute for Drug Control
Russia: Ministry of Health of the Russian Federation
South Africa: Medicines Control Council
Turkey: Ministry of Health
France: National Agency for the Safety of Medicine and Health Products
Italy: The Italian Medicines Agency
Spain: Spanish Agency of Medicines and Health Products
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Poland: Ministry of Health
Vietnam: Ministry of Health

Keywords provided by AstraZeneca:
Asthma,
Bronchial Diseases,
Respiratory Tract Diseases,
Lung Diseases,
Obstructive Lung Diseases

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on August 18, 2014