Trial Outcomes & Findings for Study to Assess Functionality, Reliability, and Performance of a Pre-filled Syringe With Benralizumab Administered at Home (NCT NCT02417961)

NCT ID: NCT02417961

Last Updated: 2018-05-23

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 162 participants
• Primary outcome timeframe: Week 12, Week 16, and Weeks 12 and 16
• Results posted on: 2018-05-23

Participant Flow

162 participants signed informed consent, 116 participants receive treatment with benralizumab 30 mg at every 4 weeks schedule.

Participant milestones

Measure	Benra 30 mg Benralizumab administered subcutaneously every 4 weeks
Overall Study STARTED	116
Overall Study COMPLETED	112
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure	Benra 30 mg Benralizumab administered subcutaneously every 4 weeks
Overall Study Adverse Event	1
Overall Study Lost to Follow-up	1
Overall Study Withdrawal by Subject	2

Baseline Characteristics

Study to Assess Functionality, Reliability, and Performance of a Pre-filled Syringe With Benralizumab Administered at Home

Baseline characteristics by cohort

Measure	Benra 30 mg n=116 Participants Benralizumab administered subcutaneously every 4 weeks
Age, Continuous	47.6 years STANDARD_DEVIATION 13.19 • n=5 Participants
Sex: Female, Male Female	64 Participants n=5 Participants
Sex: Female, Male Male	52 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Benra 30 mg n=116 Participants Benralizumab administered subcutaneously every 4 weeks
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
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
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

PRIMARY outcome

Timeframe: Week 12, Week 16

Population: Full analysis set - all patients who were administered for at least one dose of Benralizumab.

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.

Outcome measures

Measure	Benra 30 mg n=116 Participants Benralizumab administered subcutaneously every 4 weeks
Number and Percentage of Returned APFS Used to Administer Benralizumab at Home That Have Been Evaluated as Functional Week 16	108 Participants
Number and Percentage of Returned APFS Used to Administer Benralizumab at Home That Have Been Evaluated as Functional Week 12	113 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Benra 30 mg n=573 Accessorized Pre-filled Syringe Benralizumab administered subcutaneously every 4 weeks
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
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
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
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
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
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
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
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

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Benra 30 mg n=116 Participants Benralizumab administered subcutaneously every 4 weeks
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
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 0.80
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
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
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

SECONDARY outcome

Timeframe: 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.

Mean PK Concentration at each visit

Outcome measures

Measure	Benra 30 mg n=116 Participants Benralizumab administered subcutaneously every 4 weeks
The Pharmacokinetics (PK) of Benralizumab in the Terms of PK Parameters: Serum Concentration of Benralizumab Baseline	NA ng/mL Geometric Coefficient of Variation NA Value is less than lower limit of quantification
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
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
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

SECONDARY outcome

Timeframe: Baseline, Week 20, and Week 28

Population: Full analysis set - all patients who were administered for at least one dose of Benralizumab.

Blood eosinophil counts by timepoint

Outcome measures

Measure	Benra 30 mg n=116 Participants Benralizumab administered subcutaneously every 4 weeks
The Pharmacodynamics of Benralizumab in the Terms of Peripheral Blood Eosinophil Levels Week 28	47.1 cells/ uL Standard Deviation 141.50
The Pharmacodynamics of Benralizumab in the Terms of Peripheral Blood Eosinophil Levels Baseline	362.2 cells/ uL Standard Deviation 322.01
The Pharmacodynamics of Benralizumab in the Terms of Peripheral Blood Eosinophil Levels Week 20	13.0 cells/ uL Standard Deviation 56.33

SECONDARY outcome

Timeframe: Baseline until Week 28

Population: Full analysis set - all patients who were administered for at least one dose of Benralizumab.

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

Outcome measures

Measure	Benra 30 mg n=116 Participants Benralizumab administered subcutaneously every 4 weeks
The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) Positive at any visit	17 Participants
The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) Base- and Post-baseline Positive	2 Participants
The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) Only post-baseline positive	13 Participants
The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) Only baseline positive	2 Participants
The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) Persistently Positive	14 Participants
The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) Transiently Positive	1 Participants

Adverse Events

Benra 30 mg

Serious events: 7 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Measure	Benra 30 mg n=116 participants at risk Benralizumab administered subcutaneously every 4 weeks
Gastrointestinal disorders Colitis	0.86% 1/116 • Number of events 1
Gastrointestinal disorders Large intestine polyp	0.86% 1/116 • Number of events 1
General disorders Non-cardiac chest pain	0.86% 1/116 • Number of events 1
Infections and infestations Diverticulitis	0.86% 1/116 • Number of events 1
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.86% 1/116 • Number of events 1
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.86% 1/116 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.86% 1/116 • Number of events 1
Nervous system disorders Syncope	0.86% 1/116 • Number of events 1

Other adverse events

Measure	Benra 30 mg n=116 participants at risk Benralizumab administered subcutaneously every 4 weeks
Infections and infestations Bronchitis	3.4% 4/116 • Number of events 4
Infections and infestations Nasopharyngitis	13.8% 16/116 • Number of events 19
Infections and infestations Sinusitis	5.2% 6/116 • Number of events 7
Infections and infestations Upper respiratory tract infection	11.2% 13/116 • Number of events 14
Infections and infestations Viral upper respiratory tract infection	4.3% 5/116 • Number of events 5
Musculoskeletal and connective tissue disorders Back pain	3.4% 4/116 • Number of events 4
Nervous system disorders Headache	5.2% 6/116 • Number of events 10

Additional Information

Mitchell Goldman, Global Clinical Lead Benralizumab

AstraZeneca

Phone: +1 301 398 0323

Email: Mitchell.Goldman@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee ≥ 60 days prior to submission of material for publication/presentation, Institution and PI shall jointly provide AZ with material for review. No publication/presentation may include any of AZ's Confidential Information without AZ's written approval. AZ can request Inst. and PI to withhold material from submission for publication/presentation for an additional 90 days to allow AZ to establish and preserve its proprietary rights in the material being submitted for publication or presentation.
• Publication restrictions are in place

Restriction type: OTHER