Clinical trial NCT02417961: Study to Assess Functionality, Reliability, and Performance of a Pre-filled Syringe With Benralizumab Administered at Home
Official title: A Multicenter, Open-Label, Functionality, Reliability, and Performance Study of an Accessorized Pre-filled Syringe With Home-administered Subcutaneous Benralizumab in Adult Patients With Severe Asthma (GREGALE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma,
Bronchial Diseases,
Respiratory Tract Diseases,
Lung Diseases,
Obstructive Lung Diseases,
Benralizumab
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2015-04-16
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to assess functionality, performance, and reliability of an accessorized pre-filled syringe (APFS) with benralizumab administered subcutaneously (SC) in an at-home setting reported by the patient or caregiver, and to confirm the safety and clinical benefit of benralizumab administration in asthma patients with severe asthma.


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
* Male and female patients aged 18 to 75 years of age at the time of Visit 1
* Patient or caregiver must be willing and able to self-administer the IP (Investigational product). Caregiver must be age of consent or older at the time of Visit 1, if applicable
* Weight of ≥40 kg
* Evidence of asthma as documented by either: Airway reversibility (FEV1 ≥12% and 200 ml) demonstrated at Visit 1 or 2 OR documented in the previous 12 months OR; Airflow variability in FEV1 ≥20% between pulmonary function testing documented in the 12 months prior to V2 OR; Airflow variability shown by \>20% diurnal variability in peak flow observed in the patient's asthma action plan
* Documented history of current treatment with ICS (Inhaled corticosteroids) and LABA (Long-acting β2 agonists). 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. For ICS/LABA combination preparations, both the mid- and high-strength maintenance doses approved in the local country will meet this ICS criterion. Additional asthma controller medications (e.g., LTRAs (Leukotriene receptor antagonists), tiotropium, theophylline, oral corticosteroids) are allowed
* Morning pre-bronchodilator (pre-BD) FEV1 of \>50% predicted at Visit 1 or Visit 2
* Not well controlled asthma as documented by either: An ACQ6 (Asthma Control Questionnaire 6) ≥1.5 OR; A peak flow of 60-80% predicted OR; An exacerbation, one or more, that required oral or systemic corticosteroids in the previous year OR; Any one of the following assessed by patient recall over the previous 2-4 weeks: Asthma symptoms \>2 days/week; OR / Nighttime awakenings 1 or more/week; OR / Short acting beta2-agonist use for symptom control (not for prevention of exercise induced asthma) \>2 days/week

Exclusion criteria:

* Clinically important pulmonary disease other than asthma (eg, active lung infection, COPD (Chronic obstructive pulmonary disease), 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; Influence 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 IP 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 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

Primary outcomes:
measure: Number and Percentage of Patients/Caregivers Who Successfully Administered Benralizumab 30 mg Subcutaneously (SC) by Injection With an APFS at Home
timeFrame: Week 12, Week 16, and Weeks 12 and 16
measure: Number and Percentage of Returned APFS Used to Administer Benralizumab at Home That Have Been Evaluated as Functional
timeFrame: Week 12, Week 16
measure: Number and Percentage of APFS Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints)
timeFrame: Weeks 0, 4, 8, 12, 16, 0 to 8, 12 to 16, and 0 to 16
Secondary outcomes:
measure: The Effect of Benralizumab on Asthma Control Metrics in Terms of Change From Baseline in Mean Asthma Control Questionnaire-6 (ACQ-6) Score
timeFrame: Week 0 (baseline) and weeks 4, 8, 12, 16, 20
measure: The Pharmacokinetics (PK) of Benralizumab in the Terms of PK Parameters: Serum Concentration of Benralizumab
timeFrame: Baseline, Week 8, Week 20, and Week 28
measure: The Pharmacodynamics of Benralizumab in the Terms of Peripheral Blood Eosinophil Levels
timeFrame: Baseline, Week 20, and Week 28
measure: The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA)
timeFrame: Baseline until Week 28
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: Research Site
state: California
city: Walnut Creek
country: United States
facility: Research Site
state: California
city: Celebration
country: United States
facility: Research Site
state: Florida
city: Ocala
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Winter Park
country: United States
facility: Research Site
state: Florida
city: Albany
country: United States
facility: Research Site
state: Georgia
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Bellevue
country: United States
facility: Research Site
state: Nebraska
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Calgary
country: Canada
facility: Research Site
state: Alberta
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: Mississauga
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Pointe-Claire
country: Canada
facility: Research Site
state: Quebec
city: Quebec City
country: Canada
facility: Research Site
state: Quebec
city: St Charles Borromee
country: Canada
facility: Research Site
state: Quebec
city: Trois-Rivières
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
Study officials:
affiliation: Pulmonary Research Institute of Southeast Michigan
name: Gary T. Ferguson, MD, PC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ferguson GT, Mansur AH, Jacobs JS, Hebert J, Clawson C, Tao W, Wu Y, Goldman M. Assessment of an accessorized pre-filled syringe for home-administered benralizumab in severe asthma. J Asthma Allergy. 2018 Apr 5;11:63-72. doi: 10.2147/JAA.S157762. eCollection 2018.