Trial Outcomes & Findings for Study to Assess Functionality, Reliability, and Performance of a Single-Use Auto-Injector With Benralizumab Administered at Home (NCT NCT02918071)

NCT ID: NCT02918071

Last Updated: 2018-11-02

Results Overview

Patients who are still in the study is defined as patients who had been treated for the specified timepoint. A successful administration is defined as an injection completed, an answer of "Yes" to all 5 questions in the Questionnaire, and adequately passed the visual inspection and function tests.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 121 participants
• Primary outcome timeframe: Week 12, Week 16, Week 12 and 16
• Results posted on: 2018-11-02

Participant Flow

121 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	121
Overall Study COMPLETED	118
Overall Study NOT COMPLETED	3

Reasons for withdrawal

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

Baseline Characteristics

Full analysis set

Baseline characteristics by cohort

Measure	Benra 30 mg n=121 Participants Benralizumab administered subcutaneously every 4 weeks
Age, Continuous	48.5 Years STANDARD_DEVIATION 14.95 • n=5 Participants • Full analysis set
Sex: Female, Male Female	77 Participants n=5 Participants • Full analysis set
Sex: Female, Male Male	44 Participants n=5 Participants • Full analysis set
Race/Ethnicity, Customized White	97 Participants n=5 Participants • Full analysis set
Race/Ethnicity, Customized Black or African American	14 Participants n=5 Participants • Full analysis set
Race/Ethnicity, Customized Asian	9 Participants n=5 Participants • Full analysis set
Race/Ethnicity, Customized Other	1 Participants n=5 Participants • Full analysis set

PRIMARY outcome

Timeframe: Week 12, Week 16, Week 12 and 16

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

Patients who are still in the study is defined as patients who had been treated for the specified timepoint. A successful administration is defined as an injection completed, an answer of "Yes" to all 5 questions in the Questionnaire, and adequately passed the visual inspection and function tests.

Outcome measures

Measure	Benra 30mg n=121 Participants Benralizumab administered subcutaneously every 4 weeks
Number of Patients/Caregivers Who Successfully Administered Benralizumab 30 mg Subcutaneously (SC) by Injection With an AI Device at Home Week 12	113 Participants
Number of Patients/Caregivers Who Successfully Administered Benralizumab 30 mg Subcutaneously (SC) by Injection With an AI Device at Home Week 16	112 Participants
Number of Patients/Caregivers Who Successfully Administered Benralizumab 30 mg Subcutaneously (SC) by Injection With an AI Device at Home Week 12 and 16	108 Participants

PRIMARY outcome

Timeframe: Week 12, Week 16

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

AI evaluated as functional is defined as the device having adequately passed the visual inspection and function tests.

Outcome measures

Measure	Benra 30mg n=234 Auto-injector Benralizumab administered subcutaneously every 4 weeks
Number of Returned AI Devices Used to Administer Benralizumab at Home That Have Been Evaluated as Functional Week 12	114 Auto-injector
Number of Returned AI Devices Used to Administer Benralizumab at Home That Have Been Evaluated as Functional Week 16	113 Auto-injector

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 auto-injector used at each time point.

Number (%) of AI used to administer benralizumab at home or in the clinic and have been reported as malfunctioning (Product Complaints). The percentage is calculated based on AI dispensed for patients who were treated for the specific time point. This excludes AIs dispensed but never used for the treatment or the device not returned for evaluation.

Outcome measures

Measure	Benra 30mg n=595 Auto-injector Benralizumab administered subcutaneously every 4 weeks
Number of AI Devices Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints) Week 0	0 Auto-injector
Number of AI Devices Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints) Week 4	1 Auto-injector
Number of AI Devices Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints) Week 8	1 Auto-injector
Number of AI Devices Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints) Week 12	3 Auto-injector
Number of AI Devices Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints) Week 16	4 Auto-injector
Number of AI Devices Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints) Week 0 to Week 8	2 Auto-injector
Number of AI Devices Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints) Week 12 to Week 16	7 Auto-injector
Number of AI Devices Used to Administer Benralizumab at Home or in the Clinic and Have Been Reported as Malfunctioning (Product Complaints) Week 0 to Week 16	9 Auto-injector

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 30mg n=121 Participants Benralizumab administered subcutaneously every 4 weeks
Change From Baseline in Mean Asthma Control Questionnaire-6 (ACQ-6) Score Week 4	-0.63 Scores on a scale Standard Deviation 0.99
Change From Baseline in Mean Asthma Control Questionnaire-6 (ACQ-6) Score Week 8	-0.91 Scores on a scale Standard Deviation 1.05
Change From Baseline in Mean Asthma Control Questionnaire-6 (ACQ-6) Score Week 12	-1.07 Scores on a scale Standard Deviation 1.02
Change From Baseline in Mean Asthma Control Questionnaire-6 (ACQ-6) Score Week 16	-1.13 Scores on a scale Standard Deviation 1.06
Change From Baseline in Mean Asthma Control Questionnaire-6 (ACQ-6) Score Week 20	-1.04 Scores on a scale Standard Deviation 1.08

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 30mg n=121 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	698.18 ng/mL Geometric Coefficient of Variation 186.455
The Pharmacokinetics (PK) of Benralizumab in the Terms of PK Parameters: Serum Concentration of Benralizumab Week 20	787.51 ng/mL Geometric Coefficient of Variation 280.788
The Pharmacokinetics (PK) of Benralizumab in the Terms of PK Parameters: Serum Concentration of Benralizumab Week 28	62.86 ng/mL Geometric Coefficient of Variation 469.359

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 30mg n=121 Participants Benralizumab administered subcutaneously every 4 weeks
The Pharmacodynamics of Benralizumab in the Terms of Peripheral Blood Eosinophil Levels Baseline	230 cells/ uL Interval 150.0 to 360.0
The Pharmacodynamics of Benralizumab in the Terms of Peripheral Blood Eosinophil Levels Week 20	20 cells/ uL Interval 10.0 to 30.0
The Pharmacodynamics of Benralizumab in the Terms of Peripheral Blood Eosinophil Levels Week 28	20 cells/ uL Interval 10.0 to 50.0

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 30mg n=121 Participants Benralizumab administered subcutaneously every 4 weeks
The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) Positive at any visit	9 Participants
The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) Base- and Post-baseline Positive	0 Participants
The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) Only post-baseline positive	9 Participants
The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) Only baseline positive	0 Participants
The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) Persistently Positive	8 Participants
The Immunogenicity of Benralizumab in the Terms of Anti-drug Antibodies (ADA) Transiently Positive	1 Participants

Adverse Events

Benra 30 mg

Serious events: 1 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Measure	Benra 30 mg n=121 participants at risk Benralizumab administered subcutaneously every 4 weeks
Respiratory, thoracic and mediastinal disorders Asthma	0.83% 1/121 • Number of events 1 • 28 weeks. Adverse events were collected from the time the patient signed the informed consent, throughout the treatment period and including the follow-up period (through Week 28). Serious adverse events were recorded from the time of informed consent.

Other adverse events

Measure	Benra 30 mg n=121 participants at risk Benralizumab administered subcutaneously every 4 weeks
Immune system disorders Seasonal allergy	3.3% 4/121 • Number of events 4 • 28 weeks. Adverse events were collected from the time the patient signed the informed consent, throughout the treatment period and including the follow-up period (through Week 28). Serious adverse events were recorded from the time of informed consent.
Infections and infestations Bronchitis	3.3% 4/121 • Number of events 4 • 28 weeks. Adverse events were collected from the time the patient signed the informed consent, throughout the treatment period and including the follow-up period (through Week 28). Serious adverse events were recorded from the time of informed consent.
Infections and infestations Respiratory tract infection viral	3.3% 4/121 • Number of events 5 • 28 weeks. Adverse events were collected from the time the patient signed the informed consent, throughout the treatment period and including the follow-up period (through Week 28). Serious adverse events were recorded from the time of informed consent.
Infections and infestations Upper respiratory tract infection	8.3% 10/121 • Number of events 11 • 28 weeks. Adverse events were collected from the time the patient signed the informed consent, throughout the treatment period and including the follow-up period (through Week 28). Serious adverse events were recorded from the time of informed consent.
Infections and infestations Viral upper respiratory tract infection	14.9% 18/121 • Number of events 22 • 28 weeks. Adverse events were collected from the time the patient signed the informed consent, throughout the treatment period and including the follow-up period (through Week 28). Serious adverse events were recorded from the time of informed consent.
Nervous system disorders Headache	6.6% 8/121 • Number of events 8 • 28 weeks. Adverse events were collected from the time the patient signed the informed consent, throughout the treatment period and including the follow-up period (through Week 28). Serious adverse events were recorded from the time of informed consent.
Respiratory, thoracic and mediastinal disorders Asthma	8.3% 10/121 • Number of events 14 • 28 weeks. Adverse events were collected from the time the patient signed the informed consent, throughout the treatment period and including the follow-up period (through Week 28). Serious adverse events were recorded from the time of informed consent.

Additional Information

Ubaldo Martin, Global Clinical Lead Benralizumab

AstraZeneca

Phone: +1 301 398 0163

Email: Ubaldo.Martin@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