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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
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Benralizumab | Experimental | 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. |
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| Placebo | Placebo Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Benralizumab | Drug | Benralizumab SC administered every 4 weeks for 3 doses (Weeks 0, 4, and 8). |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | 4 weeks |
| 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. | 12 weeks |
| 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. | 4 weeks |
| 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. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 12 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pamela L Zeitlin, M.D. Ph.D. | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Birmingham | Alabama | 35209 | United States | ||
| Research Site |
Not provided
| Label | URL |
|---|---|
| CSP redacted | View source |
| Statistical Analysis Plan (SAP) | View source |
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The study duration was up to 23 weeks, consisting of an initial screening period lasting up to 3 weeks, a 12-week treatment period, and a follow-up visit 8 weeks after the last dose of study drug
This study was conducted at 30 study centers in the United States between 01 July 2016 and 24 January 2017
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| ID | Title | Description |
|---|---|---|
| FG000 | Benralizumab 30mg | Benralizumab 30mg/day subcutaneous |
| FG001 | Placebo | Placebo to benralizumab subcutaneous |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 14, 2015 | Dec 12, 2017 |
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| Benralizumab Placebo | Drug | Placebo administered every 4 weeks for 3 doses (Weeks 0, 4, and 8). |
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| Seasonal influenza virus vaccine | Drug | Patients will receive 1 dose of seasonal influenza virus vaccine Intramuscular (IM) at Week 8. |
|
| 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. | 4 weeks |
| 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. | 12 weeks |
| 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. | 4 weeks |
| 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 | 12 weeks |
| Mesa |
| Arizona |
| 85206 |
| United States |
| Research Site | Huntington Beach | California | 92647 | United States |
| Research Site | Newport Beach | California | 92663 | United States |
| Research Site | Aurora | Colorado | 80012-4016 | United States |
| Research Site | Colorado Springs | Colorado | 80907 | United States |
| Research Site | Denver | Colorado | 80230 | United States |
| Research Site | Aventura | Florida | 33180 | United States |
| Research Site | Miami | Florida | 33135 | United States |
| Research Site | Miami | Florida | 33173 | United States |
| Research Site | Minneapolis | Minnesota | 55402 | United States |
| Research Site | Bellevue | Nebraska | 68123 | United States |
| Research Site | Northfield | New Jersey | 08225 | United States |
| Research Site | Edmond | Oklahoma | 73034 | United States |
| Research Site | Oklahoma City | Oklahoma | 73103 | United States |
| Research Site | Medford | Oregon | 97504 | United States |
| Research Site | North Charleston | South Carolina | 29420 | United States |
| Research Site | Arlington | Texas | 76018 | United States |
| Research Site | El Paso | Texas | 79903 | United States |
| Research Site | New Braunfels | Texas | 78130 | United States |
| Research Site | San Antonio | Texas | 78221 | United States |
| Research Site | San Antonio | Texas | 78251 | United States |
| Research Site | Waco | Texas | 76712 | United States |
| Research Site | Clinton | Utah | 84015 | United States |
| ALIZE\_redacted\_protocol.pdf |
| View source |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Benralizumab 30mg | Benralizumab 30mg/day subcutaneous |
| BG001 | Placebo | Placebo to benralizumab subcutaneous |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Age, Customized | Number | Participants |
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| Sex/Gender, Customized | Number | Participants |
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| Race/Ethnicity, Customized | Number | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The vaccine immunogenicity analysis set included all randomized patients who received ≥1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or microneutralization antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response. | Posted | Geometric Least Squares Mean | Standard Error | Fold change | 4 weeks |
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| Primary | 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. | The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response. | Posted | Geometric Least Squares Mean | Standard Error | Antibody titer | 12 weeks |
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| Primary | 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. | The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response. | Posted | Number | 90% Confidence Interval | Proportion of Participants | 4 weeks |
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| Primary | 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. | The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response. | Posted | Number | 90% Confidence Interval | Proportion of Participants | 12 weeks |
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| Secondary | 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. | The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response. | Posted | Number | 90% Confidence Interval | Proportion of Participants | 12 weeks |
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| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response. | Posted | Geometric Mean | Geometric Coefficient of Variation | Fold change | 4 weeks |
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| Secondary | 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. | The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response. | Posted | Geometric Mean | Geometric Coefficient of Variation | Antibody titer | 12 weeks |
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| Secondary | 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. | The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response. | Posted | Number | 90% Confidence Interval | Proportion of Participants | 4 weeks |
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| Secondary | 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 | The full analysis set included all patients who were randomized and received any investigational product. | Posted | Mean | Full Range | Score on a scale | 12 weeks |
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All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Benralizumab 30mg | Benralizumab 30mg/day subcutaneous | 0 | 51 | 0 | 51 | 28 | 51 |
| EG001 | Placebo | Placebo to benralizumab subcutaneous | 0 | 52 | 2 | 52 | 23 | 52 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Suicidal ideation | Psychiatric disorders | MedDRA 19.1 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 19.1 | Systematic Assessment |
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| Gastroenteritis viral | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA 19.1 | Systematic Assessment |
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| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 19.1 | Systematic Assessment |
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| Costochondritis | Musculoskeletal and connective tissue disorders | MedDRA 19.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 19.1 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 19.1 | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA 19.1 | Systematic Assessment |
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At least 30 days prior to submission 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 Institution 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/presentation.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mitchell Goldman MD, PhD | AstraZeneca | +1 610 457 5585 | Mitchell.Goldman@astrazeneca.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 6, 2017 | Dec 12, 2017 | SAP_001.pdf |
| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C571386 | benralizumab |
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| ≥18 to ≤21 |
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| Male |
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| Black Or African American |
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| Other |
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| White |
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| Influenza B Yamagata lineage |
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| Influenza B Victoria lineage |
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Influenza A H3N2
| ANCOVA |
The linear model effects are treatment group as a fixed effect and age group (adolescents and young adults) as fixed categorical covariate. |
| Geometric least-square mean ratio |
| 1.19 |
| 2-Sided |
| 90 |
| 0.82 |
| 1.71 |
| Other |
| Influenza B Yamagata lineage | ANCOVA | The linear model effects are treatment group as a fixed effect and age group (adolescents and young adults) as fixed categorical covariate. | Geometric least-square mean ratio | 0.93 | 2-Sided | 90 | 0.67 | 1.29 | Other |
| Influenza B Victoria lineage | ANCOVA | The linear model effects are treatment group as a fixed effect and age group (adolescents and young adults) as fixed categorical covariate. | Geometric least-square mean ratio | 0.80 | 2-Sided | 90 | 0.54 | 1.19 | Other |
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