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

Asthma Clinical Trial

— 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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02814643
• Other study ID #: D3250C00033
• Status: Completed
• Phase: Phase 3
• Start date: July 1, 2016
• Est. completion date: January 24, 2017

Study information

• Verified date: October 2018
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: January 24, 2017
• Est. primary completion date: January 24, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 21 Years

Eligibility

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 ß2 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

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Benralizumab
Benralizumab SC administered every 4 weeks for 3 doses (Weeks 0, 4, and 8).
• Benralizumab Placebo
Placebo administered every 4 weeks for 3 doses (Weeks 0, 4, and 8).
• Seasonal influenza virus vaccine
Patients will receive 1 dose of seasonal influenza virus vaccine Intramuscular (IM) at Week 8.

Locations

Country	Name	City	State
United States	Research Site	Arlington	Texas
United States	Research Site	Aurora	Colorado
United States	Research Site	Aventura	Florida
United States	Research Site	Bellevue	Nebraska
United States	Research Site	Birmingham	Alabama
United States	Research Site	Clinton	Utah
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Denver	Colorado
United States	Research Site	Edmond	Oklahoma
United States	Research Site	El Paso	Texas
United States	Research Site	Huntington Beach	California
United States	Research Site	Medford	Oregon
United States	Research Site	Mesa	Arizona
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	New Braunfels	Texas
United States	Research Site	Newport Beach	California
United States	Research Site	North Charleston	South Carolina
United States	Research Site	Northfield	New Jersey
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	Waco	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	4 weeks
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.	12 weeks
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.	4 weeks
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.	12 weeks
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.	12 weeks
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.	4 weeks
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.	12 weeks
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.	4 weeks
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 ß2 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

External Links

•   ALIZE_redacted_protocol.pdf
•   CSP redacted
•   Statistical Analysis Plan (SAP)