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

Study identifier:D3250C00029

ClinicalTrials.gov identifier:NCT02417961

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

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)

Medical condition

asthma

Phase

Phase 3

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

162

Study type

Interventional

Age

18 Years - 75 Years

Date

Study Start Date: 27 Apr 2015

Primary Completion Date: 14 Mar 2016

Study Completion Date: 14 Mar 2016

Study design

Allocation: N/A
Endpoint Classification: Safety/Efficacy
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Apr 2018 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Exclusion 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
- 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

Location

Research Site

Pointe-Claire, QC, Canada

Location

Research Site

Vancouver, BC, Canada

Location

Research Site

Trois-Rivières, QC, Canada

Location

Research Site

Burlington, ON, Canada

Location

Research Site

Montreal, QC, Canada

Location

Research Site

Calgary, AB, Canada

Location

Research Site

Fountain Valley, CA, United States

Location

Research Site

Orlando, FL, United States

Arms	Assigned Interventions
Experimental: Benralizumab 30 mg Benralizumab administered subcutaneously every 4 weeks	Biological/Vaccine: Benralizumab Benralizumab administered subcutaneously every 4 weeks Other Name: Benralizumab

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
162 participants signed informed consent, 116 participants receive treatment with benralizumab 30 mg at every 4 weeks schedule.

Reporting Groups

	Description
Benra 30 mg	Benralizumab administered subcutaneously every 4 weeks

Participant Flow: Overall Study

	Benra 30 mg
STARTED	116
COMPLETED	112
NOT COMPLETED	4
Adverse Event	1
Lost to Follow-up	1
Withdrawal by Subject	2

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Benra 30 mg	Benralizumab administered subcutaneously every 4 weeks

Baseline Measures

	Benra 30 mg
Number of Participants [units: Participants]	116
Age Continuous [units: years] Mean ± Standard Deviation	47.6 ± 13.19
Gender, Male/Female [units: ]
Female	64
Male	52

Outcome Measures

1. Primary Outcome Measure: Number and percentage of patients/caregivers who successfully administered benralizumab 30 mg subcutaneously (SC) by injection with an APFS at home [ Time Frame: Week 12, Week 16, and Weeks 12 and 16 ]

Measure Type	Primary
Measure Name	Number and percentage of patients/caregivers who successfully administered benralizumab 30 mg subcutaneously (SC) by injection with an APFS at home
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set - all patients who were administered for at least one dose of Benralizumab.

Reporting Groups

	Description
Benra 30 mg	Benralizumab administered subcutaneously every 4 weeks

Measured Values

	Benra 30 mg
Number of Participants Analyzed [units:participants]	116
Number and percentage of patients/caregivers who successfully administered benralizumab 30 mg subcutaneously (SC) by injection with an APFS at home [units: ]
Week 12	112
Week 16	108
Weeks 12 and 16	106

Statistical Analysis 1 for Number and percentage of patients/caregivers who successfully administered benralizumab 30 mg subcutaneously (SC) by injection with an APFS at home

Groups^[1]	All groups
Method^[3]	Other [Clopper-pearson Exact CI]
Other^[5]	98.2
95% Confidence Interval	( 93.81 to 99.79 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	One sample Confidence Interval (Week 12)
[5]	Other relevant estimation information:
	Percentage of patients who successfully administered benralizumab with an APFS at home (Week 12)

Statistical Analysis 2 for Number and percentage of patients/caregivers who successfully administered benralizumab 30 mg subcutaneously (SC) by injection with an APFS at home

Groups^[1]	All groups
Method^[3]	Other [Clopper-pearson Exact CI]
Other^[5]	99.1
95% Confidence Interval	( 94.99 to 99.98 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	One sample Confidence Interval (Week 16)
[5]	Other relevant estimation information:
	Percentage of patients who successfully administered benralizumab with an APFS at home (Week 16)

Statistical Analysis 3 for Number and percentage of patients/caregivers who successfully administered benralizumab 30 mg subcutaneously (SC) by injection with an APFS at home

Groups^[1]	All groups
Method^[3]	Other [Clopper-pearson Exact CI]
Other^[5]	93.0
95% Confidence Interval	( 86.64 to 96.92 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	One sample Confidence Interval (Week 12 and 16)
[5]	Other relevant estimation information:
	Percentage of patients who successfully administered benralizumab with an APFS at home (Week 12 and 16)

2. Primary Outcome Measure: Number and percentage of returned APFS used to administer benralizumab at home that have been evaluated as functional [ Time Frame: Week 12, Week 16 ]

Measure Type	Primary
Measure Name	Number and percentage of returned APFS used to administer benralizumab at home that have been evaluated as functional
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set - all patients who were administered for at least one dose of Benralizumab.

Reporting Groups

	Description
Benra 30 mg	Benralizumab administered subcutaneously every 4 weeks

Measured Values

	Benra 30 mg
Number of Participants Analyzed [units:participants]	116
Number and percentage of returned APFS used to administer benralizumab at home that have been evaluated as functional [units: ]
Week 12	113
Week 16	108

Statistical Analysis 1 for Number and percentage of returned APFS used to administer benralizumab at home that have been evaluated as functional

Groups^[1]	All groups
Method^[3]	Other [Clopper-pearson Exact CI]
Other^[5]	99.1
95% Confidence Interval	( 95.21 to 99.98 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	One sample Confidence Interval (Week 12)
[5]	Other relevant estimation information:
	Percentage of patients returned functional APFS administered at home (Week 12)

Statistical Analysis 2 for Number and percentage of returned APFS used to administer benralizumab at home that have been evaluated as functional

Groups^[1]	All groups
Method^[3]	Other [Clopper Pearson Exact CI]
Other^[5]	99.1
95% Confidence Interval	( 94.99 to 99.98 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	One sample confidence interval (Week 16)
[5]	Other relevant estimation information:
	Percentage of patients returned functional APFS administered at home (Week 16)

3. Primary Outcome Measure: Number and percentage of APFS used to administer benralizumab at home or in the clinic and have been reported as malfunctioning (Product Complaints) [ Time Frame: Weeks 0, 4, 8, 12, 16, 0 to 8, 12 to 16, and 0 to 16 ]

Measure Type	Primary
Measure Name	Number and percentage of APFS used to administer benralizumab at home or in the clinic and have been reported as malfunctioning (Product Complaints)
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of Units analyzed per row represents number of accessorized pre-filled syringes used at each time point.

Reporting Groups

	Description
Benra 30 mg	Benralizumab administered subcutaneously every 4 weeks

Measured Values

	Benra 30 mg
Number of Participants Analyzed [units:participants]	116
Number of Accessorized Pre-filled Syringe Analyzed	573
Number and percentage of APFS used to administer benralizumab at home or in the clinic and have been reported as malfunctioning (Product Complaints) [units: ]
Week 0	0
Week 4	1
Week 8	0
Week 12	0
Week 16	0
Week 0 to 8	1
Week 12 to 16	0
Week 0 to 16	1

Statistical Analysis 1 for Number and percentage of APFS used to administer benralizumab at home or in the clinic and have been reported as malfunctioning (Product Complaints)

Groups^[1]	All groups
Method^[3]	Other [Clopper-pearson Exact CI]
Other^[5]	0.0
95% Confidence Interval	( 0.00 to 3.13 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	One sample Confidence Interval (Week 0)
[5]	Other relevant estimation information:
	Percentage of mulfunctioning APFS used to administer benralizumab at home or clinic (Week 0)

Statistical Analysis 2 for Number and percentage of APFS used to administer benralizumab at home or in the clinic and have been reported as malfunctioning (Product Complaints)

Groups^[1]	All groups
Method^[3]	Other [Clopper-pearson Exact CI]
Other^[5]	0.9
95% Confidence Interval	( 0.02 to 4.67 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	One sample Confidence Interval (Week 4)
[5]	Other relevant estimation information:
	Percentage of malfunctioning APFS used to administer benralizumab at home or clinic (Week 4)

Statistical Analysis 3 for Number and percentage of APFS used to administer benralizumab at home or in the clinic and have been reported as malfunctioning (Product Complaints)

Groups^[1]	All groups
Method^[3]	Other [Clopper-pearson Exact CI]
Other^[5]	0.0
95% Confidence Interval	( 0.00 to 3.16 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	One sample Confidence Interval (Week 8)
[5]	Other relevant estimation information:
	Percentage of malfunctioning APFS used to administer benralizumab at home or clinic (Week 8)

Statistical Analysis 4 for Number and percentage of APFS used to administer benralizumab at home or in the clinic and have been reported as malfunctioning (Product Complaints)

Groups^[1]	All groups
Method^[3]	Other [Clopper-pearson Exact CI]
Other^[5]	0.0
95% Confidence Interval	( 0.00 to 3.13 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	One sample Confidence Interval (Week 12)
[5]	Other relevant estimation information:
	Percentage of malfunctioning APFS used to administer benralizumab at home or clinic (Week 12)

Statistical Analysis 5 for Number and percentage of APFS used to administer benralizumab at home or in the clinic and have been reported as malfunctioning (Product Complaints)

Groups^[1]	All groups
Method^[3]	Other [Clopper-Pearson Exact CI]
Other^[5]	0
95% Confidence Interval	( 0 to 3.33 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	One sample Confidence Interval (Week 16)
[5]	Other relevant estimation information:
	Percentage of malfunctioning APFS used to administer benralizumab at home or clinic (Week 16)

Statistical Analysis 6 for Number and percentage of APFS used to administer benralizumab at home or in the clinic and have been reported as malfunctioning (Product Complaints)

Groups^[1]	All groups
Method^[3]	Other [Clopper-pearson Exact CI]
Other^[5]	0.3
95% Confidence Interval	( 0.01 to 1.59 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	One sample Confidence Interval (Week 0 to 8)
[5]	Other relevant estimation information:
	Percentage of malfunctioning APFS used to administer benralizumab at home or clinic (Week 0 to 8)

Statistical Analysis 7 for Number and percentage of APFS used to administer benralizumab at home or in the clinic and have been reported as malfunctioning (Product Complaints)

Groups^[1]	All groups
Method^[3]	Other [Clopper-pearson Exact CI]
Other^[5]	0.0
95% Confidence Interval	( 0.00 to 1.63 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	One sample Confidence Interval (Week 12 to 16)
[5]	Other relevant estimation information:
	Percentage of malfunctioning APFS used to administer benralizumab at home or clinic (Week 12 to 16)

Statistical Analysis 8 for Number and percentage of APFS used to administer benralizumab at home or in the clinic and have been reported as malfunctioning (Product Complaints)

Groups^[1]	All groups
Method^[3]	Other [Clopper-pearson Exact CI]
Other^[5]	0.2
95% Confidence Interval	( 0.00 to 0.97 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	One sample Confidence Interval (Week 0 to 16)
[5]	Other relevant estimation information:
	Percentage of malfunctioning APFS used to administer benralizumab at home or clinic (Week 0 to 16)

4. Secondary Outcome Measure: The effect of benralizumab on asthma control metrics in terms of change from baseline in mean Asthma Control Questionnaire-6 (ACQ-6) score [ Time Frame: Week 0 (baseline) and weeks 4, 8, 12, 16, 20 ]

Measure Type	Secondary
Measure Name	The effect of benralizumab on asthma control metrics in terms of change from baseline in mean Asthma Control Questionnaire-6 (ACQ-6) score
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set - all patients who were administered for at least one dose of Benralizumab.

Reporting Groups

	Description
Benra 30 mg	Benralizumab administered subcutaneously every 4 weeks

Measured Values

	Benra 30 mg
Number of Participants Analyzed [units:participants]	116
The effect of benralizumab on asthma control metrics in terms of change from baseline in mean Asthma Control Questionnaire-6 (ACQ-6) score [units: Scores on a scale] Mean (Standard Deviation)
Week 4	-0.53 (0.71)
Week 8	-0.54 (0.80)
Week 12	-0.72 (0.86)
Week 16	-0.82 (0.87)
Week 20	-0.73 (0.93)

No statistical analysis provided for The effect of benralizumab on asthma control metrics in terms of change from baseline in mean Asthma Control Questionnaire-6 (ACQ-6) score

5. Secondary Outcome Measure: The pharmacokinetics (PK) of benralizumab in the terms of PK parameters: serum concentration of benralizumab [ Time Frame: Baseline, Week 8, Week 20, and Week 28 ]

Measure Type	Secondary
Measure Name	The pharmacokinetics (PK) of benralizumab in the terms of PK parameters: serum concentration of benralizumab
Measure Description	Mean PK Concentration at each visit
Time Frame	Baseline, Week 8, Week 20, and Week 28
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK analysis set - include all patients who had at least one quantifiable serum PK observation post first dose of Benralizumab.

Reporting Groups

	Description
Benra 30 mg	Benralizumab administered subcutaneously every 4 weeks

Measured Values

	Benra 30 mg
Number of Participants Analyzed [units:participants]	116
The pharmacokinetics (PK) of benralizumab in the terms of PK parameters: serum concentration of benralizumab [units: ng/mL] Geometric Mean (Geometric Coefficient of Variation)
Baseline	NA (NA%)^[1]
Week 8	1031.644 (53.547%)
Week 20	802.197 (267.033%)
Week 28	56.330 (499.728%)

No statistical analysis provided for The pharmacokinetics (PK) of benralizumab in the terms of PK parameters: serum concentration of benralizumab

6. Secondary Outcome Measure: The pharmacodynamics of benralizumab in the terms of peripheral blood eosinophil levels [ Time Frame: Baseline, Week 20, and Week 28 ]

Measure Type	Secondary
Measure Name	The pharmacodynamics of benralizumab in the terms of peripheral blood eosinophil levels
Measure Description	Blood eosinophil counts by timepoint
Time Frame	Baseline, Week 20, and Week 28
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set - all patients who were administered for at least one dose of Benralizumab.

Reporting Groups

	Description
Benra 30 mg	Benralizumab administered subcutaneously every 4 weeks

Measured Values

	Benra 30 mg
Number of Participants Analyzed [units:participants]	116
The pharmacodynamics of benralizumab in the terms of peripheral blood eosinophil levels [units: cells/ uL] Mean (Standard Deviation)
Baseline	362.2 (322.01)
Week 20	13.0 (56.33)
Week 28	47.1 (141.50)

No statistical analysis provided for The pharmacodynamics of benralizumab in the terms of peripheral blood eosinophil levels

7. Secondary Outcome Measure: The immunogenicity of benralizumab in the terms of anti-drug antibodies (ADA) [ Time Frame: Baseline until Week 28 ]

Measure Type	Secondary
Measure Name	The immunogenicity of benralizumab in the terms of anti-drug antibodies (ADA)
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set - all patients who were administered for at least one dose of Benralizumab.

Reporting Groups

	Description
Benra 30 mg	Benralizumab administered subcutaneously every 4 weeks

Measured Values

	Benra 30 mg
Number of Participants Analyzed [units:participants]	116
The immunogenicity of benralizumab in the terms of anti-drug antibodies (ADA) [units: Participants]
Positive at any visit	17
Base- and Post-baseline Positive	2
Only post-baseline positive	13
Only baseline positive	2
Persistently Positive	14
Transiently Positive	1

No statistical analysis provided for The immunogenicity of benralizumab in the terms of anti-drug antibodies (ADA)

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
Benra 30 mg	Benralizumab administered subcutaneously every 4 weeks

Serious Adverse Events

Benra 30 mg

Total, serious adverse events

# participants affected / at risk

7/116 (6.03%)

Gastrointestinal disorders

Colitis¹,^†

# participants affected / at risk

1/116 (0.86%)

# events

Gastrointestinal disorders

Large intestine polyp¹,^†

# participants affected / at risk

1/116 (0.86%)

# events

General disorders and administration site conditions

Non-cardiac chest pain¹,^†

# participants affected / at risk

1/116 (0.86%)

# events

Infections and infestations

Diverticulitis¹,^†

# participants affected / at risk

1/116 (0.86%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain¹,^†

# participants affected / at risk

1/116 (0.86%)

# events

Musculoskeletal and connective tissue disorders

Spinal column stenosis¹,^†

# participants affected / at risk

1/116 (0.86%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Papillary thyroid cancer¹,^†

# participants affected / at risk

1/116 (0.86%)

# events

Nervous system disorders

Syncope¹,^†

# participants affected / at risk

1/116 (0.86%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 18.1

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	3%

Reporting Groups

	Description
Benra 30 mg	Benralizumab administered subcutaneously every 4 weeks

Other Adverse Events

Benra 30 mg

Total, other (not including serious) adverse events

# participants affected / at risk

43/116 (37.07%)

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

4/116 (3.45%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

16/116 (13.79%)

# events

Infections and infestations

Sinusitis¹,^†

# participants affected / at risk

6/116 (5.17%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

13/116 (11.21%)

# events

Infections and infestations

Viral upper respiratory tract infection¹,^†

# participants affected / at risk

5/116 (4.31%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

4/116 (3.45%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

6/116 (5.17%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 18.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: ≥ 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Mitchell Goldman, Global Clinical Lead Benralizumab
Organization:	AstraZeneca
Phone	+1 301 398 0323
E-mail:	[email protected]

Documents available

http://doi.org/10.2147/JAA.S157762
Download
Redacted CSP
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Contact Backup

AstraZeneca Clinical Study Information

+1 800-236-9933

information.center@astrazeneca.com

Investigators

Principal Investigator

Gary T. Ferguson

Pulmonary Research Institute of Southeast Michigan

Sponsors

Collaborators

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

http://doi.org/10.2147/JAA.S157762

Redacted CSP

Trial Results Summaries