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

Phase 3

Completed

Conditions: Healthy or Stable Underlying Chronic Medical Condition

Interventions: Biological: FluMist/B/Yamagata
Biological: FluMist/B/Victoria
Biological: Q/LAIV-BFS (MEDI8662)

Registration Number: NCT00952705

Lead Sponsor: MedImmune LLC

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1800

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FluMist/B/Yamagata	FluMist/B/Yamagata	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)
FluMist/B/Victoria	FluMist/B/Victoria	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).
Q/LAIV-BFS (MEDI8662)	Q/LAIV-BFS (MEDI8662)	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).

Primary Outcome Measures

Name	Time	Method
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).	Day 28 to 35	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.

Secondary Outcome Measures

Name	Time	Method
The Percentage of Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the B/Yamagata Strain in All Participants, Regardless of Baseline Serostatus.	Day 0 and Day 28-35	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.
The Percentage of Serosusceptible Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the A/H1N1 Strain.	Day 28-35	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).
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.	Day 0 and Day 28-35	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).
The Percentage of Serosusceptible Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the A/H1N1 Strain.	Day 0 and Day 28-35	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).
The Percentage of Serosusceptible Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the B/Victoria Strain.	Day 0 and Day 28-35	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.
The Percentage of Seropositive Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the A/H3N2 Strain.	Day 0 and Day 28-35	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).
The Percentage of Seropositive Subjects Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the B/Victoria Strain.	Day 0 and Day 28-35	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.
The Percentage of Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the B/Victoria Strain in All Participants, Regardless of Baseline Serostatus.	Day 0 and Day 28-35	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.
The Percentage of Serosusceptible Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the B/Yamagata Strain.	Day 0 and Day 28-35	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.
The Percentage of Serosusceptible Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the A/H3N2 Strain.	Day 0 and Day 28-35	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).
The Percentage of Seropositive Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the A/H1N1 Strain.	Day 0 and Day 28-35	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).
The Percentage of Seropositive Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the B/Yamagata Strain.	Day 0 and Day 28-35	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.
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.	Day 28-35	The comparators to the A/H1N1 and A/H3N2 strains were participants in the All FluMist group (combined data for both FluMist arms).
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.	Day 28-35	The comparator for the B/Yamagata strain was participants in the FluMist/B/Yamagata arm.
The Percentage of Seropositive Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the A/H1N1 Strain.	Day 28-35	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).
The Percentage of Seropositive Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the A/H3N2 Strain.	Day 28-35	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).
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.	Day 28-35	The comparator for the B/Victoria strain was participants in the FluMist/B/Victoria arm.
The Percentage of Serosusceptible Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the A/H3N2 Strain.	Day 28-35	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).
The Percentage of Serosusceptible Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the B/Yamagata Strain.	Day 28-35	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.
The Percentage of Serosusceptible Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the B/Victoria Strain.	Day 28-35	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.
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 Seropositive Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the B/Yamagata Strain.	Day 28-35	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.
The Percentage of Seropositive Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the B/Victoria Strain.	Day 28-35	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.
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 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 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

Trial Locations

Locations (16): Coastal Clinical Research, Inc.
🇺🇸
Mobile, Alabama, United States
Miami Research Associates
🇺🇸
Miami, Florida, United States
Benchmark Research
🇺🇸
Metairie, Louisiana, United States
Avail Clinical Research, LLC
🇺🇸
DeLand, Florida, United States
Tampa Bay Medical Research, Inc.
🇺🇸
Clearwater, Florida, United States
Clinical Research Atlanta
🇺🇸
Stockbridge, Georgia, United States
Sundance Clinical Research
🇺🇸
Saint Louis, Missouri, United States
Regional Clinical Research
🇺🇸
Endwell, New York, United States
Rochester Clinical Research Inc.
🇺🇸
Rochester, New York, United States
Palmetto Medical Research
🇺🇸
Mount Pleasant, South Carolina, United States
Benchmark Research Ft. Worth
🇺🇸
Fort Worth, Texas, United States
Vince and Associates Clinical Research
🇺🇸
Overland Park, Kansas, United States
Johnson County Clin-Trials
🇺🇸
Lenexa, Kansas, United States
California Research Foundation
🇺🇸
San Diego, California, United States
Meridian Clinical Research, LLC
🇺🇸
Omaha, Nebraska, United States
Benchmark Research Austin
🇺🇸
Austin, Texas, United States