Clinical trial NCT02322775: Study to Evaluate the Efficacy and Safety of Benralizumab in Adult Patients With Mild to Moderate Persistent Asthma
Official title: A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Benralizumab in Adult Patients With Mild to Moderate Persistent Asthma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive Lung Diseases,
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2014-12-23
Enrollment: 211
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to confirm the safety and clinical benefit of benralizumab administration in asthma patients with mild to moderate persistent asthma in order to gain an understanding of the benefit/risk of benralizumab across the spectrum of asthma disease.


Eligibility criteria: Inclusion Criteria:

Written informed consent for study participation must be obtained prior to any study related procedures being performed and according to international guidelines and/or applicable European Union (EU) guidelines.

* Female and male aged 18 to 75 years, inclusively, at the time of Visit 1.
* Weight of ≥40 kg.
* Evidence of asthma as documented by post-bronchodilator (post-BD) reversibility in FEV1 of ≥ 12% demonstrated at Visit 2.
* Documented use of 1 of the following types of asthma therapy at time of informed consent: Low- to medium-dose ICS (ie, 100 to 500 μg fluticasone dry powder formulation equivalents total daily dose) with or without other controller medications, eg, an LTRA and/or theophylline or Low-dose ICS/LABA fixed combination therapy (eg, the lowest regular maintenance dose approved in the local country will meet this criterion)
* Morning pre-bronchodilator (pre-BD) FEV1 of \> 50% to ≤ 90% predicted at Visit 2.

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, 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
* nfluence the findings of the studies or their interpretations,- Impede the patient's ability to complete the entire duration of study.
* Known history of allergy or reaction to the investigational product formulation.
* History of anaphylaxis to any biologic therapy.- History of Guillain-Barré syndrome.
* A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to standard of care therapy.- 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.
* Any clinically significant abnormal findings in physical examination, vital signs, 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.
* 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.
* A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
* History of cancer:
* Patients who have had basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible provided that the patient is in remission and curative therapy was completed at least 12 months prior to the date informed consent was obtained.
* Patients who have had other malignancies are eligible provided that the patient is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained

Primary outcomes:
measure: Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (L) at Week 12
timeFrame: Baseline, Week 4, Week 8 and Week 12
Secondary outcomes:
measure: Change From Baseline in Morning Peak Expiratory Flow (PEF) (L/Min) at Home at Week 12
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
measure: Change From Baseline in Evening Peak Expiratory Flow (PEF) (L/Min) at Home at Week 12
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
measure: Change From Baseline in Total Asthma Symptom Score at Week 12
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
measure: Change From Baseline in Total Asthma Rescue Medication Use (Puffs) at Week 12
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
measure: Change From Baseline in Proportion of Nights With Nocturnal Awakenings at Week 12
timeFrame: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
measure: Change From Baseline in Mean ACQ-6 Score at Week 12
timeFrame: Baseline, Week 4, Week 8 and Week 12
measure: Asthma Exacerbations
timeFrame: Up to Week 12
measure: Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
timeFrame: Baseline and Week 12
measure: Serum Concentrations (ng/mL)
timeFrame: Baseline, Week 12 and Week 20
measure: Peripheral Blood Eosinophil Levels
timeFrame: Baseline, Week 12 and Week 20
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Rolling Hills Estates
country: United States
facility: Research Site
state: California
city: Clearwater
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Blue Island
country: United States
facility: Research Site
state: Illinois
city: Skillman
country: United States
facility: Research Site
state: New Jersey
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Monroe
country: United States
facility: Research Site
state: North Carolina
city: Raleigh
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Grove City
country: United States
facility: Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Medford
country: United States
facility: Research Site
state: Oregon
city: Spartanburg
country: United States
facility: Research Site
state: South Carolina
city: El Paso
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Ajax
country: Canada
facility: Research Site
state: Ontario
city: Burlington
country: Canada
facility: Research Site
state: Ontario
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: St Charles Borromee
country: Canada
facility: Research Site
state: Quebec
city: Trois Rivieres
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Quebec
country: Canada
facility: Research Site
city: Bamberg
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Frankfurt/Main
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Neu-Isenburg
country: Germany
facility: Research Site
city: Balassagyarmat
country: Hungary
facility: Research Site
city: Komárom
country: Hungary
facility: Research Site
city: Miskolc
country: Hungary
facility: Research Site
city: Pécs
country: Hungary
facility: Research Site
city: Pécs
country: Hungary
facility: Research Site
city: Százhalombatta
country: Hungary
facility: Research Site
city: Katowice
country: Poland
facility: Research Site
city: Mrągowo
country: Poland
facility: Research Site
city: Ostrów Wielkopolski
country: Poland
facility: Research Site
city: Pabianice
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Tarnów
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Humenne
country: Slovakia
facility: Research Site
city: Kosice
country: Slovakia
facility: Research Site
city: Levice
country: Slovakia
facility: Research Site
city: Poprad
country: Slovakia
facility: Research Site
city: Presov
country: Slovakia
facility: Research Site
city: Vrable
country: Slovakia
facility: Research Site
city: Zilina
country: Slovakia
facility: Research Site
Study officials:
affiliation: Pulmonary Research Institute of Southeast Michigan
name: Gary T. Ferguson, M.D.,P.C.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ferguson GT, FitzGerald JM, Bleecker ER, Laviolette M, Bernstein D, LaForce C, Mansfield L, Barker P, Wu Y, Jison M, Goldman M; BISE Study Investigators. Benralizumab for patients with mild to moderate, persistent asthma (BISE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2017 Jul;5(7):568-576. doi: 10.1016/S2213-2600(17)30190-X. Epub 2017 May 22.