A Study to Evaluate the Immunogenicity of Quadrivalent Live Attenuated Influenza Vaccine (LAIV) in Children

A Randomized, Double-Blind, Active Controlled Study to Evaluate the Immunogenicity of Quadrivalent LAIV in Children

The primary objective of this study is to demonstrate the immunologic noninferiority of Q/LAIV to FluMist in children 2 to 17 years of age.

The randomized, double-blind study was designed to demonstrate the immunologic noninferiority of Q/LAIV compared to FluMist in children 2-17 years by comparing the strain-specific post-dose geometric mean titers of hemagglutination inhibition antibodies. Children were randomized 3:1:1 to receive Q/LAIV or one of two FluMist vaccines. Subjects 9-17 years of age received a single dose, and those 2-8 years of age received two doses one month apart. Serum was obtained 1 month after dose 1 except in influenza vaccine-naive subjects 2-8 years old, when it was obtained after dose 2. Safety and tolerability were also assessed.

Inclusion Criteria:

• Male or female
• Age 2 through 17 years at the time of randomization
• Written informed consent and any locally required authorization (eg, HIPAA in the USA, EU Data Privacy Directive in the EU, and written informed assent if applicable) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
• Females of childbearing potential, unless surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), has sterile male partner, is premenarchal, or practices abstinence, must have used an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, cervical cap with spermicide, or use of a condom with spermicide by the sexual partner) for 30 days prior to the first dose of investigational product, and must agree to continue using such precautions for 60 days after the final dose of investigational product
• A subject who is considered by the investigator to be at risk of pregnancy must also have a negative urine pregnancy test at screening and, if screening and Day 0 do not occur on the same day, on the day of vaccination prior to randomization. Investigator judgment is required to assess each subject's need for pregnancy testing
• Healthy by medical history and physical examination OR presence of stable underlying chronic medical condition for which hospitalization has not been required in the previous year
• Able to complete follow-up period of 180 days post last dose of vaccine as required by the protocol
• Subject/legal representative is available by telephone
• Child's legal representative is able to understand and comply with the requirements of the protocol, as judged by the investigator

Exclusion Criteria:

• Acute illness or evidence of significant active infection at randomization;
• Fever ≥ 100.4°F (38.0°C) at randomization
• History of asthma, or in children < 5 years of age, history of recurrent wheezing
• Any drug therapy from 15 days prior to randomization or expected drug therapy through 28 days post last dose with the exception of the following classes/types of medications, which are allowed:
• Contraceptives (change in contraceptive type or method is acceptable as long as guidelines are followed for prevention of pregnancy during change);
• Topical corticosteroids, calcineurin inhibitors, or antifungals for uncomplicated dermatitis;
• Chronic medications (including those taken on an as-needed basis) that have been well tolerated and were not initiated and/or did not have a dosage change within 90 days prior to randomization.
• Current or expected receipt of immunosuppressive medications within a 28 day window around any dose, including an immunosuppressive dose of corticosteroids, which is defined as ≥ 20 mg/day of prednisone or its equivalent, given daily or on alternate days for ≥ 15 days) (intranasal, intra-articular, and topical corticosteroids are permitted); Note: topical corticosteroids for uncomplicated dermatitis may be used throughout the study according to the judgment of the investigator; topical calcineurin inhibitors may be used in accordance with their package insert at entry and during study participation
• Receipt of immunoglobulin or blood products within 90 days before randomization into the study or expected receipt during study participation
• Receipt of any investigational drug therapy within 28 days prior to Dose 1 or planned receipt of any investigational drug therapy through 90 days after final dosing of investigational product (use of licensed agents for indications not listed in the package insert is permitted)
• Receipt of any nonstudy vaccine within 28 days prior to randomization or planned receipt of nonstudy vaccine through 28 days after final dosing
• Receipt of any nonstudy seasonal influenza vaccine within 90 days of Dose 1 or planned receipt of nonstudy seasonal influenza vaccine prior to 35 days post last dose of investigational product
• Any known immunosuppressive condition or immune deficiency disease including known or suspected infection with human immunodeficiency virus (HIV)
• History of allergic disease or reactions likely to be exacerbated by any component of the investigational product including allergy to eggs, egg proteins, gentamicin, or gelatin or serious, life threatening, or severe reactions to previous influenza vaccinations
• Use of aspirin or salicylate-containing products within 28 days prior to randomization or expected receipt through 28 days after final vaccination;
• History of Guillain-Barré syndrome
• Use of antiviral agents with activity against influenza virus (including amantadine, rimantadine, oseltamivir, and zanamivir) within 28 days prior to first dose of investigational product or anticipated use of such agents within 28 days after last scheduled vaccination
• Known or suspected mitochondrial encephalomyopathy
• Pregnant or lactating female
• History of alcohol or drug abuse that, in the opinion of the investigator, would affect the subject's safety or compliance with study
• Any condition that, in the opinion of the investigator, might compromise the safety of the subject in the study or would interfere with evaluation of the safety or immunogenicity of the investigational products
• Subject, legal representative, or immediate family member of subject who is an employee of the clinical study site or who is otherwise involved with the conduct of the study
• A history of epilepsy, seizure, or an evolving neurological condition except that of a single febrile seizure that occurred 3 or more years prior to enrollment would not disqualify a subject

Note: an individual who initially is excluded from study participation based on one or more of the above time-limited criteria may be reconsidered for enrollment once the condition has resolved as long as the subject continues to meet all other entry criteria and the same SID number is used