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 (ALIZE)

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.

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

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Benralizumab; Drug: Seasonal influenza virus vaccine; Drug: Benralizumab Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Research Site
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Research Site
  • California
    • Huntington Beach, California, United States, 92647
      • Research Site
    • Newport Beach, California, United States, 92663
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80012-4016
      • Research Site
    • Colorado Springs, Colorado, United States, 80907
      • Research Site
    • Denver, Colorado, United States, 80230
      • Research Site
  • Florida
    • Aventura, Florida, United States, 33180
      • Research Site
    • Miami, Florida, United States, 33173
      • Research Site
    • Miami, Florida, United States, 33135
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Research Site
  • Nebraska
    • Bellevue, Nebraska, United States, 68123
      • Research Site
  • New Jersey
    • Northfield, New Jersey, United States, 08225
      • Research Site
  • Oklahoma
    • Edmond, Oklahoma, United States, 73034
      • Research Site
    • Oklahoma City, Oklahoma, United States, 73103
      • Research Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • Research Site
  • South Carolina
    • North Charleston, South Carolina, United States, 29420
      • Research Site
  • Texas
    • Arlington, Texas, United States, 76018
      • Research Site
    • El Paso, Texas, United States, 79903
      • Research Site
    • New Braunfels, Texas, United States, 78130
      • Research Site
    • San Antonio, Texas, United States, 78251
      • Research Site
    • San Antonio, Texas, United States, 78221
      • Research Site
    • Waco, Texas, United States, 76712
      • Research Site
  • Utah
    • Clinton, Utah, United States, 84015
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Benralizumab; 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.	Drug: Benralizumab; Benralizumab SC administered every 4 weeks for 3 doses (Weeks 0, 4, and 8).; Drug: Seasonal influenza virus vaccine; Patients will receive 1 dose of seasonal influenza virus vaccine Intramuscular (IM) at Week 8.
Placebo Comparator: Placebo; 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.	Drug: Seasonal influenza virus vaccine; Patients will receive 1 dose of seasonal influenza virus vaccine Intramuscular (IM) at Week 8.; Drug: Benralizumab Placebo; Placebo administered every 4 weeks for 3 doses (Weeks 0, 4, and 8).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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
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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Pamela L Zeitlin, M.D. Ph.D., Johns Hopkins University

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): January 24, 2017
• Study Completion (Actual): January 24, 2017

Study Registration Dates

• First Submitted: June 15, 2016
• First Submitted That Met QC Criteria: June 23, 2016
• First Posted (Estimate): June 28, 2016

Study Record Updates

• Last Update Posted (Actual): October 24, 2018
• Last Update Submitted That Met QC Criteria: October 23, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: severe asthma; Male and female adolescent patients
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Asthmatic Agents; Respiratory System Agents; Benralizumab
• Other Study ID Numbers: D3250C00033