Back to resultsStudy to Evaluate the Potential Effect of Benralizumab on the Humoral Immune Response to the Seasonal Influenza Vaccination in Adolescent and Young Adult Patients With Severe Asthma (ALIZE)
Primary Purpose
Asthma
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Benralizumab
Benralizumab Placebo
Seasonal influenza virus vaccine
Sponsored by
About this trial
This is an interventional supportive care trial for Asthma focused on measuring Male and female adolescent patients, severe asthma
Eligibility Criteria
Inclusion Criteria:
- Female and male patients aged 12 to 21 years, inclusive, at the time of Visit 1
- Weight of ≥40 kg
- Documented history of current treatment with Inhaled corticosteroids (ICS) and long-acting β2 agonists (LABA)
- Morning pre-bronchodilator forced expiratory volume in 1 second (FEV1) of >50% predicted at Visit 1 or Visit 2.
- Airway reversibility (FEV1 >12% and 200 ml) demonstrated at Visit 1 or Visit 2 using the Maximum Post-bronchodilator Procedure OR
- Airway reversibility documented in the previous 12 months prior to Visit 1
- An exacerbation, 1 or more, that required oral corticosteroids in the previous year OR
- Any condition assessed by patient recall over the previous 2-4 weeks
Exclusion Criteria:
- Clinically important pulmonary disease other than asthma
- Known history of allergy or reaction to the Investigational Product formulation or influenza vaccine
- Receipt of an influenza vaccine within 90 days prior to randomization
- Poorly controlled asthma during the screening period that requires treatment with oral corticosteroids or a hospitalization/emergency room visit for the treatment of asthma
- Acute illness or evidence of significant active infection or known influenza infection during the current flu season
Sites / Locations
- Research Site
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Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Benralizumab
Placebo
Arm Description
1 mL fill volume administered every 4 weeks for 3 doses (Weeks 0, 4, and 8). Patients will receive 1 dose of seasonal influenza virus vaccine Intramuscular (IM) at Week 8.
1 mL fill volume administered every 4 weeks for 3 doses (Weeks 0, 4, and 8). Patients will receive 1 dose of seasonal influenza virus vaccine Intramuscular (IM) at Week 8.
Outcomes
Primary Outcome Measures
Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12
To compare the geometric mean fold rises in influenza strain-specific hemagglutination-inhibition responses from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. Geometric mean fold rise was defined as antilog(z) (mean [log(z) x]), where "x" is the postdose HAI antibody titer fold rise from Week 8 and "z" is the natural logarithm.
Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12
To compare the geometric mean titers of hemagglutination-inhibition antibody as a measure of influenza strain-specific response at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12
To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥4-fold rises in hemagglutination-inhibition antibody titer from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12
To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥40-fold rises in hemagglutination-inhibition antibody titer at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Secondary Outcome Measures
Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12
To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥320-fold rises in hemagglutination-inhibition antibody titer at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12
To compare the geometric mean fold rises in influenza strain-specific microneutralization antibody responses from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. Geometric mean fold rise was defined as antilog(z) (mean [log(z) x]), where "x" is the postdose microneutralization antibody titer fold rise from Week 8 and "z" is the natural logarithm.
Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12
To compare the geometric mean titers of microneutralization antibody as a measure of influenza strain-specific response at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12
To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥4-fold rises in microneutralization antibody titer from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Change From Baseline in Mean Asthma Control Questionnaire 6 (ACQ-6) Score at Week 12
To compare the change from baseline at Week 12 in mean ACQ-6 score between patients receiving benralizumab 30mg and patients receiving placebo. The ACQ-6 assesses asthma symptoms (nighttime waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and short-acting β2 agonist use). Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is the mean of the responses to each question. Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and ≤1.5 indicate partly controlled asthma, and a score >1.5 indicates not well controlled asthma
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02814643
Brief Title
Study to Evaluate the Potential Effect of Benralizumab on the Humoral Immune Response to the Seasonal Influenza Vaccination in Adolescent and Young Adult Patients With Severe Asthma
Acronym
ALIZE
Official Title
A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase 3b Study to Evaluate the Potential Effect of Benralizumab on the Humoral Immune Response to the Seasonal Influenza Vaccination in Adolescent and Young Adult Patients With Severe Asthma.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
July 1, 2016 (Actual)
Primary Completion Date
January 24, 2017 (Actual)
Study Completion Date
January 24, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a randomized, double-blind, parallel group, placebo-controlled study designed to investigate the potential effect of a fixed dose of benralizumab administered subcutaneously (SC) on antibody responses following seasonal influenza virus vaccination
Detailed Description
This study is designed to investigate the potential effect of benralizumab on the antibody response to the seasonal influenza virus vaccine in patients 12-21 years of age with asthma. Benralizumab will be given subcutaneously (SC) at Weeks 0, 4, and 8 weeks, at which time benralizumab levels will reach steady state. Patients will then receive 1 dose of intramuscular (IM) seasonal influenza virus vaccine at Week 8 and samples drawn at Week 8 and Week 12 to measure the antibody response to the influenza virus
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
Male and female adolescent patients, severe asthma
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
103 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Benralizumab
Arm Type
Experimental
Arm Description
1 mL fill volume administered every 4 weeks for 3 doses (Weeks 0, 4, and 8). Patients will receive 1 dose of seasonal influenza virus vaccine Intramuscular (IM) at Week 8.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
1 mL fill volume administered every 4 weeks for 3 doses (Weeks 0, 4, and 8). Patients will receive 1 dose of seasonal influenza virus vaccine Intramuscular (IM) at Week 8.
Intervention Type
Drug
Intervention Name(s)
Benralizumab
Intervention Description
Benralizumab SC administered every 4 weeks for 3 doses (Weeks 0, 4, and 8).
Intervention Type
Drug
Intervention Name(s)
Benralizumab Placebo
Intervention Description
Placebo administered every 4 weeks for 3 doses (Weeks 0, 4, and 8).
Intervention Type
Drug
Intervention Name(s)
Seasonal influenza virus vaccine
Intervention Description
Patients will receive 1 dose of seasonal influenza virus vaccine Intramuscular (IM) at Week 8.
Primary Outcome Measure Information:
Title
Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12
Description
To compare the geometric mean fold rises in influenza strain-specific hemagglutination-inhibition responses from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. Geometric mean fold rise was defined as antilog(z) (mean [log(z) x]), where "x" is the postdose HAI antibody titer fold rise from Week 8 and "z" is the natural logarithm.
Time Frame
4 weeks
Title
Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12
Description
To compare the geometric mean titers of hemagglutination-inhibition antibody as a measure of influenza strain-specific response at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Time Frame
12 weeks
Title
Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12
Description
To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥4-fold rises in hemagglutination-inhibition antibody titer from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Time Frame
4 weeks
Title
Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12
Description
To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥40-fold rises in hemagglutination-inhibition antibody titer at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12
Description
To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥320-fold rises in hemagglutination-inhibition antibody titer at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Time Frame
12 weeks
Title
Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12
Description
To compare the geometric mean fold rises in influenza strain-specific microneutralization antibody responses from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. Geometric mean fold rise was defined as antilog(z) (mean [log(z) x]), where "x" is the postdose microneutralization antibody titer fold rise from Week 8 and "z" is the natural logarithm.
Time Frame
4 weeks
Title
Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12
Description
To compare the geometric mean titers of microneutralization antibody as a measure of influenza strain-specific response at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Time Frame
12 weeks
Title
Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12
Description
To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥4-fold rises in microneutralization antibody titer from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Time Frame
4 weeks
Title
Change From Baseline in Mean Asthma Control Questionnaire 6 (ACQ-6) Score at Week 12
Description
To compare the change from baseline at Week 12 in mean ACQ-6 score between patients receiving benralizumab 30mg and patients receiving placebo. The ACQ-6 assesses asthma symptoms (nighttime waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and short-acting β2 agonist use). Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is the mean of the responses to each question. Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and ≤1.5 indicate partly controlled asthma, and a score >1.5 indicates not well controlled asthma
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Female and male patients aged 12 to 21 years, inclusive, at the time of Visit 1
Weight of ≥40 kg
Documented history of current treatment with Inhaled corticosteroids (ICS) and long-acting β2 agonists (LABA)
Morning pre-bronchodilator forced expiratory volume in 1 second (FEV1) of >50% predicted at Visit 1 or Visit 2.
Airway reversibility (FEV1 >12% and 200 ml) demonstrated at Visit 1 or Visit 2 using the Maximum Post-bronchodilator Procedure OR
Airway reversibility documented in the previous 12 months prior to Visit 1
An exacerbation, 1 or more, that required oral corticosteroids in the previous year OR
Any condition assessed by patient recall over the previous 2-4 weeks
Exclusion Criteria:
Clinically important pulmonary disease other than asthma
Known history of allergy or reaction to the Investigational Product formulation or influenza vaccine
Receipt of an influenza vaccine within 90 days prior to randomization
Poorly controlled asthma during the screening period that requires treatment with oral corticosteroids or a hospitalization/emergency room visit for the treatment of asthma
Acute illness or evidence of significant active infection or known influenza infection during the current flu season
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pamela L Zeitlin, M.D. Ph.D.
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
Facility Name
Research Site
City
Mesa
State/Province
Arizona
ZIP/Postal Code
85206
Country
United States
Facility Name
Research Site
City
Huntington Beach
State/Province
California
ZIP/Postal Code
92647
Country
United States
Facility Name
Research Site
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
Facility Name
Research Site
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80012-4016
Country
United States
Facility Name
Research Site
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Facility Name
Research Site
City
Denver
State/Province
Colorado
ZIP/Postal Code
80230
Country
United States
Facility Name
Research Site
City
Aventura
State/Province
Florida
ZIP/Postal Code
33180
Country
United States
Facility Name
Research Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33135
Country
United States
Facility Name
Research Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33173
Country
United States
Facility Name
Research Site
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55402
Country
United States
Facility Name
Research Site
City
Bellevue
State/Province
Nebraska
ZIP/Postal Code
68123
Country
United States
Facility Name
Research Site
City
Northfield
State/Province
New Jersey
ZIP/Postal Code
08225
Country
United States
Facility Name
Research Site
City
Edmond
State/Province
Oklahoma
ZIP/Postal Code
73034
Country
United States
Facility Name
Research Site
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73103
Country
United States
Facility Name
Research Site
City
Medford
State/Province
Oregon
ZIP/Postal Code
97504
Country
United States
Facility Name
Research Site
City
North Charleston
State/Province
South Carolina
ZIP/Postal Code
29420
Country
United States
Facility Name
Research Site
City
Arlington
State/Province
Texas
ZIP/Postal Code
76018
Country
United States
Facility Name
Research Site
City
El Paso
State/Province
Texas
ZIP/Postal Code
79903
Country
United States
Facility Name
Research Site
City
New Braunfels
State/Province
Texas
ZIP/Postal Code
78130
Country
United States
Facility Name
Research Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78221
Country
United States
Facility Name
Research Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78251
Country
United States
Facility Name
Research Site
City
Waco
State/Province
Texas
ZIP/Postal Code
76712
Country
United States
Facility Name
Research Site
City
Clinton
State/Province
Utah
ZIP/Postal Code
84015
Country
United States
12. IPD Sharing Statement
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3366&filename=d3250c00033-clinical-study-protocol_Redacted.pdf
Description
CSP redacted
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3366&filename=d3250C00033-sap-edition-2_redacted.pdf
Description
Statistical Analysis Plan (SAP)
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3366&filename=ALIZE_redacted_protocol.pdf
Description
ALIZE_redacted_protocol.pdf
Learn more about this trial
Study to Evaluate the Potential Effect of Benralizumab on the Humoral Immune Response to the Seasonal Influenza Vaccination in Adolescent and Young Adult Patients With Severe Asthma
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