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)

• ClinicalTrials.gov Identifier: NCT02814643
• Recruitment Status: Completed
• First Posted: June 28, 2016
• Results First Posted: March 1, 2018
• Last Update Posted: October 24, 2018
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

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

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: Benralizumab; Drug: Benralizumab Placebo; Drug: Seasonal influenza virus vaccine	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 103 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• 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.
• Actual Study Start Date: July 1, 2016
• Actual Primary Completion Date: January 24, 2017
• Actual Study Completion Date: January 24, 2017

Arms and Interventions

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: Benralizumab Placebo; Placebo 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.

Outcome Measures

Primary Outcome Measures :

1. Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12 [ Time Frame: 4 weeks ]
   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.
2. Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12 [ Time Frame: 12 weeks ]
   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.
3. 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 [ Time Frame: 4 weeks ]
   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. Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12 [ Time Frame: 12 weeks ]
   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 :

1. Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12 [ Time Frame: 12 weeks ]
   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.
2. Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12 [ Time Frame: 4 weeks ]
   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.
3. Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12 [ Time Frame: 12 weeks ]
   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.
4. 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 [ Time Frame: 4 weeks ]
   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.
5. Change From Baseline in Mean Asthma Control Questionnaire 6 (ACQ-6) Score at Week 12 [ Time Frame: 12 weeks ]
   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

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Alabama

Research Site

Birmingham, Alabama, United States, 35209

United States, Arizona

Research Site

Mesa, Arizona, United States, 85206

United States, California

Research Site

Huntington Beach, California, United States, 92647

Research Site

Newport Beach, California, United States, 92663

United States, Colorado

Research Site

Aurora, Colorado, United States, 80012-4016

Research Site

Colorado Springs, Colorado, United States, 80907

Research Site

Denver, Colorado, United States, 80230

United States, Florida

Research Site

Aventura, Florida, United States, 33180

Research Site

Miami, Florida, United States, 33135

Research Site

Miami, Florida, United States, 33173

United States, Minnesota

Research Site

Minneapolis, Minnesota, United States, 55402

United States, Nebraska

Research Site

Bellevue, Nebraska, United States, 68123

United States, New Jersey

Research Site

Northfield, New Jersey, United States, 08225

United States, Oklahoma

Research Site

Edmond, Oklahoma, United States, 73034

Research Site

Oklahoma City, Oklahoma, United States, 73103

United States, Oregon

Research Site

Medford, Oregon, United States, 97504

United States, South Carolina

Research Site

North Charleston, South Carolina, United States, 29420

United States, Texas

Research Site

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, 78221

Research Site

San Antonio, Texas, United States, 78251

Research Site

Waco, Texas, United States, 76712

United States, Utah

Research Site

Clinton, Utah, United States, 84015

Sponsors and Collaborators

AstraZeneca

Investigators

• Principal Investigator: Pamela L Zeitlin, M.D. Ph.D.; Johns Hopkins University

  Study Documents (Full-Text)

Documents provided by AstraZeneca:

Study Protocol  [PDF] December 14, 2015

Statistical Analysis Plan  [PDF] March 6, 2017

More Information

Additional Information:

CSP redacted 

Statistical Analysis Plan (SAP) 

ALIZE_redacted_protocol.pdf 

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02814643
• Other Study ID Numbers: D3250C00033
• First Posted: June 28, 2016
• Results First Posted: March 1, 2018
• Last Update Posted: October 24, 2018
• Last Verified: October 2018

Keywords provided by AstraZeneca:

Male and female adolescent patients; severe asthma

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Benralizumab; Anti-Asthmatic Agents; Respiratory System Agents