Asthma
Conditions
Keywords
Asthma,, Bronchial Diseases,, Respiratory Tract Diseases,, Lung Diseases,, Obstructive Lung Diseases,, Benralizumab
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.
Interventions
BIOLOGICALBenralizumab
Benralizumab administered subcutaneously every 4 weeks
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage of Patients/Caregivers Who Successfully Administered Benralizumab 30 mg Subcutaneously (SC) by Injection With an APFS at Home | Week 12, Week 16, and Weeks 12 and 16 | Number (%) of patients/caregivers who successfully administered benralizumab with an APFS at home among those who have been deemed by the Principal Investigator to be suitable for at-home administration and are still in the study. A successful administration is defined as an injection completed, an answer of Yes to all 5 questions in the Functioning Device Return Questionnaire for the GREGALE Clinical Study (Appendix to the Clinical Study Protocol), and adequately passed the visual inspection and function tests. The percentage is calculated among all patients/caregivers who had been deemed by the Principal Investigator to be suitable for at home administration and were still in the study at the time point. |
| Number and Percentage of Returned APFS Used to Administer Benralizumab at Home That Have Been Evaluated as Functional | Week 12, Week 16 | Number (%) of returned APFS used to administer benralizumab at home that have been evaluated as functional among all returned APFS used to administer benralizumab at home. A functional APFS is defined as an answer of Yes to all the questions in the visual inspection and function tests. The percentage is calculated among all returned APFS at the specified time point. |
| Number and Percentage of APFS Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints) | Weeks 0, 4, 8, 12, 16, 0 to 8, 12 to 16, and 0 to 16 | Number (%) of APFS used to administer benralizumab at home or in the clinic and have been reported as malfunctioning (Product Complaints). The percentage is calculated based on APFS dispensed and used for the specified time point. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Effect of Benralizumab on Asthma Control Metrics in Terms of Change From Baseline in Mean Asthma Control Questionnaire-6 (ACQ-6) Score | Week 0 (baseline) and weeks 4, 8, 12, 16, 20 | The effect of benralizumab on asthma control metrics in terms of change from baseline in mean Asthma Control Questionnaire-6 (ACQ-6) score. ACQ-6 score is defined as the average of the first 6 items of the ACQ questionnaire on symptoms, activity limitations, and rescue medication. Baseline is defined as the last non-missing observation prior to the first dose of study treatment. ACQ-6 contains one bronchodilator question and 5 symptom questions. Questions are rated from 0 (totally controlled) to 6 (severely uncontrolled). Mean ACQ-6 score is the average of the responses. Smaller score indicates better controlled asthma. |
| The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) | Baseline until Week 28 | Anti-drug antibodies (ADA) responses at baseline and post baseline. Persistently positive is defined as positive at \>=2 post-baseline assessments (with \>=16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive is defined as having at least one post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive |
| The Pharmacokinetics (PK) of Benralizumab in the Terms of PK Parameters: Serum Concentration of Benralizumab | Baseline, Week 8, Week 20, and Week 28 | Mean PK Concentration at each visit |
| The Pharmacodynamics of Benralizumab in the Terms of Peripheral Blood Eosinophil Levels | Baseline, Week 20, and Week 28 | Blood eosinophil counts by timepoint |
Countries
Canada, United States
Participant flow
Pre-assignment details
162 participants signed informed consent, 116 participants receive treatment with benralizumab 30 mg at every 4 weeks schedule.
Participants by arm
| Arm | Count |
|---|---|
| Benra 30 mg Benralizumab administered subcutaneously every 4 weeks | 116 |
| Total | 116 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Benra 30 mg |
|---|---|
| Age, Continuous | 47.6 years STANDARD_DEVIATION 13.19 |
| Sex: Female, Male Female | 64 Participants |
| Sex: Female, Male Male | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 116 |
| other Total, other adverse events | 43 / 116 |
| serious Total, serious adverse events | 7 / 116 |
Outcome results
Primary
Number and Percentage of APFS Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints)
Number (%) of APFS used to administer benralizumab at home or in the clinic and have been reported as malfunctioning (Product Complaints). The percentage is calculated based on APFS dispensed and used for the specified time point.
Time frame: Weeks 0, 4, 8, 12, 16, 0 to 8, 12 to 16, and 0 to 16
Population: Number of Units analyzed per row represents number of accessorized pre-filled syringes used at each time point.
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Benra 30 mg | Number and Percentage of APFS Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints) | Week 0 | 0 Accessorized Pre-filled Syringe |
| Benra 30 mg | Number and Percentage of APFS Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints) | Week 4 | 1 Accessorized Pre-filled Syringe |
| Benra 30 mg | Number and Percentage of APFS Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints) | Week 8 | 0 Accessorized Pre-filled Syringe |
| Benra 30 mg | Number and Percentage of APFS Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints) | Week 12 | 0 Accessorized Pre-filled Syringe |
| Benra 30 mg | Number and Percentage of APFS Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints) | Week 16 | 0 Accessorized Pre-filled Syringe |
| Benra 30 mg | Number and Percentage of APFS Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints) | Week 0 to 8 | 1 Accessorized Pre-filled Syringe |
| Benra 30 mg | Number and Percentage of APFS Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints) | Week 12 to 16 | 0 Accessorized Pre-filled Syringe |
| Benra 30 mg | Number and Percentage of APFS Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints) | Week 0 to 16 | 1 Accessorized Pre-filled Syringe |
95% CI: [0, 3.13]Clopper-pearson Exact CI
95% CI: [0.02, 4.67]Clopper-pearson Exact CI
95% CI: [0, 3.16]Clopper-pearson Exact CI
95% CI: [0, 3.13]Clopper-pearson Exact CI
95% CI: [0, 3.33]Clopper-Pearson Exact CI
95% CI: [0.01, 1.59]Clopper-pearson Exact CI
95% CI: [0, 1.63]Clopper-pearson Exact CI
95% CI: [0, 0.97]Clopper-pearson Exact CI
Primary
Number and Percentage of Patients/Caregivers Who Successfully Administered Benralizumab 30 mg Subcutaneously (SC) by Injection With an APFS at Home
Number (%) of patients/caregivers who successfully administered benralizumab with an APFS at home among those who have been deemed by the Principal Investigator to be suitable for at-home administration and are still in the study. A successful administration is defined as an injection completed, an answer of Yes to all 5 questions in the Functioning Device Return Questionnaire for the GREGALE Clinical Study (Appendix to the Clinical Study Protocol), and adequately passed the visual inspection and function tests. The percentage is calculated among all patients/caregivers who had been deemed by the Principal Investigator to be suitable for at home administration and were still in the study at the time point.
Time frame: Week 12, Week 16, and Weeks 12 and 16
Population: Full analysis set - all patients who were administered for at least one dose of Benralizumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Benra 30 mg | Number and Percentage of Patients/Caregivers Who Successfully Administered Benralizumab 30 mg Subcutaneously (SC) by Injection With an APFS at Home | Week 12 | 112 Participants |
| Benra 30 mg | Number and Percentage of Patients/Caregivers Who Successfully Administered Benralizumab 30 mg Subcutaneously (SC) by Injection With an APFS at Home | Week 16 | 108 Participants |
| Benra 30 mg | Number and Percentage of Patients/Caregivers Who Successfully Administered Benralizumab 30 mg Subcutaneously (SC) by Injection With an APFS at Home | Weeks 12 and 16 | 106 Participants |
95% CI: [93.81, 99.79]Clopper-pearson Exact CI
95% CI: [94.99, 99.98]Clopper-pearson Exact CI
95% CI: [86.64, 96.92]Clopper-pearson Exact CI
Primary
Number and Percentage of Returned APFS Used to Administer Benralizumab at Home That Have Been Evaluated as Functional
Number (%) of returned APFS used to administer benralizumab at home that have been evaluated as functional among all returned APFS used to administer benralizumab at home. A functional APFS is defined as an answer of Yes to all the questions in the visual inspection and function tests. The percentage is calculated among all returned APFS at the specified time point.
Time frame: Week 12, Week 16
Population: Full analysis set - all patients who were administered for at least one dose of Benralizumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Benra 30 mg | Number and Percentage of Returned APFS Used to Administer Benralizumab at Home That Have Been Evaluated as Functional | Week 12 | 113 Participants |
| Benra 30 mg | Number and Percentage of Returned APFS Used to Administer Benralizumab at Home That Have Been Evaluated as Functional | Week 16 | 108 Participants |
95% CI: [95.21, 99.98]Clopper-pearson Exact CI
95% CI: [94.99, 99.98]Clopper Pearson Exact CI
Secondary
The Effect of Benralizumab on Asthma Control Metrics in Terms of Change From Baseline in Mean Asthma Control Questionnaire-6 (ACQ-6) Score
The effect of benralizumab on asthma control metrics in terms of change from baseline in mean Asthma Control Questionnaire-6 (ACQ-6) score. ACQ-6 score is defined as the average of the first 6 items of the ACQ questionnaire on symptoms, activity limitations, and rescue medication. Baseline is defined as the last non-missing observation prior to the first dose of study treatment. ACQ-6 contains one bronchodilator question and 5 symptom questions. Questions are rated from 0 (totally controlled) to 6 (severely uncontrolled). Mean ACQ-6 score is the average of the responses. Smaller score indicates better controlled asthma.
Time frame: Week 0 (baseline) and weeks 4, 8, 12, 16, 20
Population: Full analysis set - all patients who were administered for at least one dose of Benralizumab.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benra 30 mg | The Effect of Benralizumab on Asthma Control Metrics in Terms of Change From Baseline in Mean Asthma Control Questionnaire-6 (ACQ-6) Score | Week 16 | -0.82 Scores on a scale | Standard Deviation 0.87 |
| Benra 30 mg | The Effect of Benralizumab on Asthma Control Metrics in Terms of Change From Baseline in Mean Asthma Control Questionnaire-6 (ACQ-6) Score | Week 20 | -0.73 Scores on a scale | Standard Deviation 0.93 |
| Benra 30 mg | The Effect of Benralizumab on Asthma Control Metrics in Terms of Change From Baseline in Mean Asthma Control Questionnaire-6 (ACQ-6) Score | Week 4 | -0.53 Scores on a scale | Standard Deviation 0.71 |
| Benra 30 mg | The Effect of Benralizumab on Asthma Control Metrics in Terms of Change From Baseline in Mean Asthma Control Questionnaire-6 (ACQ-6) Score | Week 8 | -0.54 Scores on a scale | Standard Deviation 0.8 |
| Benra 30 mg | The Effect of Benralizumab on Asthma Control Metrics in Terms of Change From Baseline in Mean Asthma Control Questionnaire-6 (ACQ-6) Score | Week 12 | -0.72 Scores on a scale | Standard Deviation 0.86 |
Secondary
The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA)
Anti-drug antibodies (ADA) responses at baseline and post baseline. Persistently positive is defined as positive at \>=2 post-baseline assessments (with \>=16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive is defined as having at least one post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive
Time frame: Baseline until Week 28
Population: Full analysis set - all patients who were administered for at least one dose of Benralizumab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Benra 30 mg | The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) | Positive at any visit | 17 Participants |
| Benra 30 mg | The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) | Base- and Post-baseline Positive | 2 Participants |
| Benra 30 mg | The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) | Only post-baseline positive | 13 Participants |
| Benra 30 mg | The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) | Only baseline positive | 2 Participants |
| Benra 30 mg | The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) | Persistently Positive | 14 Participants |
| Benra 30 mg | The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) | Transiently Positive | 1 Participants |
Secondary
The Pharmacodynamics of Benralizumab in the Terms of Peripheral Blood Eosinophil Levels
Blood eosinophil counts by timepoint
Time frame: Baseline, Week 20, and Week 28
Population: Full analysis set - all patients who were administered for at least one dose of Benralizumab.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benra 30 mg | The Pharmacodynamics of Benralizumab in the Terms of Peripheral Blood Eosinophil Levels | Baseline | 362.2 cells/ uL | Standard Deviation 322.01 |
| Benra 30 mg | The Pharmacodynamics of Benralizumab in the Terms of Peripheral Blood Eosinophil Levels | Week 20 | 13.0 cells/ uL | Standard Deviation 56.33 |
| Benra 30 mg | The Pharmacodynamics of Benralizumab in the Terms of Peripheral Blood Eosinophil Levels | Week 28 | 47.1 cells/ uL | Standard Deviation 141.5 |
Secondary
The Pharmacokinetics (PK) of Benralizumab in the Terms of PK Parameters: Serum Concentration of Benralizumab
Mean PK Concentration at each visit
Time frame: Baseline, Week 8, Week 20, and Week 28
Population: PK analysis set - include all patients who had at least one quantifiable serum PK observation post first dose of Benralizumab.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Benra 30 mg | The Pharmacokinetics (PK) of Benralizumab in the Terms of PK Parameters: Serum Concentration of Benralizumab | Week 8 | 1031.644 ng/mL | Geometric Coefficient of Variation 53.547 |
| Benra 30 mg | The Pharmacokinetics (PK) of Benralizumab in the Terms of PK Parameters: Serum Concentration of Benralizumab | Week 20 | 802.197 ng/mL | Geometric Coefficient of Variation 267.033 |
| Benra 30 mg | The Pharmacokinetics (PK) of Benralizumab in the Terms of PK Parameters: Serum Concentration of Benralizumab | Week 28 | 56.330 ng/mL | Geometric Coefficient of Variation 499.728 |
| Benra 30 mg | The Pharmacokinetics (PK) of Benralizumab in the Terms of PK Parameters: Serum Concentration of Benralizumab | Baseline | NA ng/mL | — |