A Study to Evaluate the Immunogenicity of Quadrivalent LAIV (MEDI8662) in Adults 18 to 49 Years of Age

Study Overview
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Brief Summary
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The purpose of this study was to show that quadrivalent live attenuated influenza vaccine (Q/LAIV-BFS; MEDI8662) was at least as immunogenic as two different forms of the commercial vaccine, FluMist, by comparing the strain-specific antibody levels in the blood.

Detailed Description
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The primary objective of this study was to determine the immunologic noninferiority of MEDI8662, a quadrivalent live attenuated influenza vaccine (Q/LAIV) (delivered intranasally using the blow-fill-seal [BFS] delivery system) (Q/LAIV-BFS) to two trivalent formulations of licensed FluMist (delivered intranasally using the Becton Dickinson [BD] Accuspray™ device) by comparing the strain-specific geometric mean titers (GMTs) post dosing.

Official Title
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A Randomized, Partially Blind Active Controlled Study to Evaluate the Immunogenicity of MEDI8662 in Adults 18 to 49 Years of Age

Conditions
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Healthy or Stable Underlying Chronic Medical Condition

Intervention / Treatment
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* Biological: Q/LAIV-BFS (MEDI8662)
* Biological: FluMist/B/Yamagata
* Biological: FluMist/B/Victoria


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age 18 through 49 years, inclusive (reached their 18th year birthday but not yet reached their 50th year birthday) at the time of randomization Females of child-bearing potential, must have used an effective method of avoiding pregnancy for 30 days prior to the first dose of investigational product, and must have agreed to continue using such precautions for 60 days after the dose of investigational product. In addition, the participant must also have had a negative urine or blood 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. Healthy by medical history and physical examination OR presence of stable underlying chronic medical condition for which hospitalization had not been required in the previous year Exclusion Criteria: Acute illness or evidence of significant active infection at randomization Fever greater than or equal to 100.4 degrees F (38°C) at randomization History of asthma Any drug therapy from 15 days prior to randomization or expected drug therapy through 30 days post dose with the exception of contraceptives; topical corticosteroids or antifungals for uncomplicated dermatitis; chronic medications (including those taken on an as-needed basis) that were well tolerated and were not initiated and/or did not have a dosage change within 90 days of randomization Previous medical history or evidence of an intercurrent illness that may have compromised the safety of the participant in the study Current or expected receipt of immunosuppressive medications (inhaled and topical corticosteroids and topical calcineurin inhibitors were permitted) within a 30-day window around the dose 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 30 days prior to randomization or planned receipt of any investigational drug therapy through 30 days after dosing of investigational product (use of licensed agents for indications not listed in the package insert were permitted) Receipt of any nonstudy vaccine within 30 days prior to randomization or planned receipt of nonstudy vaccine through 30 days after dosing Receipt of any influenza vaccine (investigational or licensed) in 2009 prior to randomization or anticipated receipt prior to the collection of the post-dose immunogenicity blood sample for this study 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 Q/LAIV-BFS including allergy to eggs, egg proteins, gentamicin, or gelatin, or serious, life threatening, or severe reactions to previous influenza vaccinations History of Guillain-Barré syndrome Use of antiviral agents with activity against influenza virus (including amantadine, rimantadine, oseltamivir and zanamivir) within 30 days prior to receipt of investigational product or anticipated use within 30 days after receipt of investigational product Known or suspected mitochondrial encephalomyopathy Pregnant or lactating female Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of participant safety or study results Participant, legal guardian, or immediate family member of participant who was an employee of the clinical study site or who was otherwise involved with the conduct of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Q/LAIV-BFS (MEDI8662)<br>Q/LAIV-BFS (quadrivalent influenza vaccine) (MEDI8662) was supplied in the blow-fill-seal delivery system that delivers a nominal dose of 0.2 mL into a single nostril. Each dose contained 10^7.0 ± 0.5 fluorescent focus units (FFU) of each of 4 cold-adapted, temperature-sensitive, attenuated, 6:2 reassortant influenza virus strains: A/H1N1 (A/South Dakota/6/2007), A/H3N2 (A/Uruguay/716/2007), B/Victoria (B/Malaysia/2506/2004), and B/Yamagata (B/Florida/4/2006). | Biological: Q/LAIV-BFS (MEDI8662)<br>* A single dose of Q/LAIV-BFS delivered using the BFS delivery system (0.2 mL) on Day 0.<br>|
| Active Comparator: FluMist/B/Yamagata<br>FluMist/B/Yamagata was administered intranasally using a Becton Dickinson Accuspray™ device. A total volume of 0.2 mL was administered intranasally (approximately 0.1 mL into each nostril). Each dose contained 10^7.0 ± 0.5 FFU of each of 3 cold-adapted, temperature-sensitive, attenuated, 6:2 reassortant influenza virus strains: A/H1N1 (A/South Dakota/6/2007), A/H3N2 (A/Uruguay/716/2007), and B/Yamagata (B/Florida/4/2006) | Biological: FluMist/B/Yamagata<br>* FluMist/B/Yamagata - 0.2 mL dose at Day 0<br>|
| Active Comparator: FluMist/B/Victoria<br>FluMist/B/Victoria was administered intranasally using a BD Accuspray™ device. A total volume of 0.2 mL was administered intranasally (approximately 0.1 mL into each nostril). Each dose contained 10^7.0 ± 0.5 FFU of each of 3 cold-adapted, temperature-sensitive, attenuated, 6:2 reassortant influenza virus strains: A/H1N1 (A/South Dakota/6/2007), A/H3N2 (A/Uruguay/716/2007), and B/Victoria (B/Malaysia/2506/2004). | Biological: FluMist/B/Victoria<br>* FluMist/B/Victoria - 0.2 mL dose at Day 0<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Post Dose Strain-specific Serum Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMTs) in the Q/LAIV-BFS (MEDI8662) Arm as Compared to Those in the Combined Flumist Arms (All Flumist Group). | Noninferior immune response was assessed by evaluating the upper bound of the 2-sided 95% confidence intervals (CIs) for the ratios of strain-specific HAI GMTs for the specified comparisons. The GMT ratio = GMT in comparator (All FluMist group) divided by the GMT in the Q/LAIV-BFS arm. | Day 28 to 35 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the A/H1N1 and A/H3N2 Strains in All Participants, Regardless of Baseline Serostatus. | Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. The comparators for seroresponse to the A/H1N1 and A/H3N2 strains were participants in the All FluMist group (combined data for both FluMist arms). | Day 0 and Day 28-35 | 
| The Percentage of Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the B/Yamagata Strain in All Participants, Regardless of Baseline Serostatus. | Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. The comparator for seroresponse to the B/Yamagata strain was participants in the FluMist/B/Yamagata arm. | Day 0 and Day 28-35 | 
| The Percentage of Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the B/Victoria Strain in All Participants, Regardless of Baseline Serostatus. | Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. The comparator for seroresponse to the B/Victoria strain was participants in the FluMist/B/Victoria arm. | Day 0 and Day 28-35 | 
| The Percentage of Serosusceptible Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the A/H1N1 Strain. | Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. Participants with a baseline HAI titer ≤ 8 were considered to be serosusceptible for that strain. The comparator for seroresponse to the A/H1N1 strain was participants in the All FluMist group (combined data for both FluMist arms). | Day 0 and Day 28-35 | 
| The Percentage of Serosusceptible Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the A/H3N2 Strain. | Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. Participants with a baseline HAI titer ≤ 8 were considered to be serosusceptible for that strain. The comparator for seroresponse to the A/H3N2 strain was participants in the All FluMist group (combined data for both FluMist arms). | Day 0 and Day 28-35 | 
| The Percentage of Serosusceptible Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the B/Yamagata Strain. | Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. Participants with a baseline HAI titer ≤ 8 were considered to be serosusceptible for that strain. The comparator for seroresponse to the B/Yamagata strain was participants in the FluMist/B/Yamagata arm. | Day 0 and Day 28-35 | 
| The Percentage of Serosusceptible Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the B/Victoria Strain. | Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. Participants with a baseline HAI titer ≤ 8 were considered to be serosusceptible for that strain. The comparator for seroresponse to the B/Victoria strain was participants in the FluMist/B/Victoria arm. | Day 0 and Day 28-35 | 
| The Percentage of Seropositive Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the A/H1N1 Strain. | Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. Participants with a baseline HAI titer > 8 were considered to be seropositive for that strain. The comparator for seroresponse to the A/H1N1 strain was participants in the All FluMist group (combined data for both FluMist arms). | Day 0 and Day 28-35 | 
| The Percentage of Seropositive Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the A/H3N2 Strain. | Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. Participants with a baseline HAI titer > 8 were considered to be seropositive for that strain. The comparator for seroresponse to the A/H3N2 strain was participants in the All FluMist group (combined data for both FluMist arms). | Day 0 and Day 28-35 | 
| The Percentage of Seropositive Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the B/Yamagata Strain. | Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. Participants with a baseline HAI titer > 8 were considered to be seropositive for that strain. The comparator for seroresponse to the B/Yamagata strain was participants in the FluMist/B/Yamagata arm. | Day 0 and Day 28-35 | 
| The Percentage of Seropositive Subjects Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the B/Victoria Strain. | Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. Participants with a baseline HAI titer > 8 were considered to be seropositive for that strain. The comparator for seroresponse to the B/Victoria strain was participants in the FluMist/B/Victoria arm. | Day 0 and Day 28-35 | 
| The Percentage of Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the A/H1N1 and A/H3N2 Strains in All Participants, Regardless of Baseline Serostatus. | The comparators to the A/H1N1 and A/H3N2 strains were participants in the All FluMist group (combined data for both FluMist arms). | Day 28-35 | 
| The Percentage of Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the B/Yamagata Strain in All Participants, Regardless of Baseline Serostatus. | The comparator for the B/Yamagata strain was participants in the FluMist/B/Yamagata arm. | Day 28-35 | 
| The Percentage of Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the B/Victoria Strain in All Participants, Regardless of Baseline Serostatus. | The comparator for the B/Victoria strain was participants in the FluMist/B/Victoria arm. | Day 28-35 | 
| The Percentage of Serosusceptible Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the A/H1N1 Strain. | Participants with a baseline HAI titer ≤ 8 were considered to be serosusceptible for that strain. The comparator for the A/H1N1 strain was participants in the All FluMist group (combined data for both FluMist arms). | Day 28-35 | 
| The Percentage of Serosusceptible Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the A/H3N2 Strain. | Participants with a baseline HAI titer ≤ 8 were considered to be serosusceptible for that strain. The comparator for the A/H3N2 strain was participants in the All FluMist group (combined data for both FluMist arms). | Day 28-35 | 
| The Percentage of Serosusceptible Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the B/Yamagata Strain. | Subjects with a baseline HAI titer ≤ 8 were considered to be serosusceptible for that strain. The comparator for the B/Yamagata strain was participants in the FluMist/B/Yamagata arm. | Day 28-35 | 
| The Percentage of Serosusceptible Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the B/Victoria Strain. | Participants with a baseline HAI titer ≤ 8 were considered to be serosusceptible for that strain. The comparator for the B/Victoria strain was participants in the FluMist/B/Victoria arm. | Day 28-35 | 
| The Percentage of Seropositive Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the A/H1N1 Strain. | Participants with a baseline HAI titer > 8 were considered to be seropositive for that strain. The comparator for the A/H1N1 strain was participants in the All FluMist group (combined data for both FluMist arms). | Day 28-35 | 
| The Percentage of Seropositive Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the A/H3N2 Strain. | Participants with a baseline HAI titer > 8 were considered to be seropositive for that strain. The comparator for the A/H3N2 strain was participants in the All FluMist group (combined data for both FluMist arms). | Day 28-35 | 
| The Percentage of Seropositive Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the B/Yamagata Strain. | Participants with a baseline HAI titer > 8 were considered to be seropositive for that strain. The comparator for the B/Yamagata strain was participants in the FluMist/B/Yamagata arm. | Day 28-35 | 
| The Percentage of Seropositive Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the B/Victoria Strain. | Participants with a baseline HAI titer > 8 were considered to be seropositive for that strain. The comparator for the B/Victoria strain was participants in the FluMist/B/Victoria arm. | Day 28-35 | 
| The Percentage of Participants Experiencing Each Solicited Symptom From Administration of Investigational Product Through 14 Days Post Dose |  | Days 0-14 post dose | 
| The Percentage of Participants Reporting Any Adverse Event From Administration of Investigational Product Through 28 Days Post Dose |  | Days 0-28 post dose | 
| The Percentage of Participants Reporting Any Serious Adverse Event From Administration of Investigational Product Through 28 Days Post Dose |  | Days 0-28 post dose | 
| The Percentage of Participants Reporting Any Serious Adverse Event From Administration of Investigational Product Through 180 Days Post Dose |  | Days 0-180 post dose | 
| The Percentage of Participants Reporting New Onset Chronic Diseases From Administration of Investigational Product Through 180 Days Post Dose |  | Days 0-180 post dose |