Clinical trial NCT00952705: A Study to Evaluate the Immunogenicity of Quadrivalent LAIV (MEDI8662) in Adults 18 to 49 Years of Age
Official title: A Randomized, Partially Blind Active Controlled Study to Evaluate the Immunogenicity of MEDI8662 in Adults 18 to 49 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Healthy or Stable Underlying Chronic Medical Condition
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2009-08-06
Enrollment: 1800
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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).
timeFrame: Day 28 to 35
Secondary outcomes:
measure: 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.
timeFrame: Day 0 and Day 28-35
measure: The Percentage of Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the B/Yamagata Strain in All Participants, Regardless of Baseline Serostatus.
timeFrame: Day 0 and Day 28-35
measure: The Percentage of Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the B/Victoria Strain in All Participants, Regardless of Baseline Serostatus.
timeFrame: Day 0 and Day 28-35
measure: The Percentage of Serosusceptible Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the A/H1N1 Strain.
timeFrame: Day 0 and Day 28-35
measure: The Percentage of Serosusceptible Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the A/H3N2 Strain.
timeFrame: Day 0 and Day 28-35
measure: The Percentage of Serosusceptible Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the B/Yamagata Strain.
timeFrame: Day 0 and Day 28-35
measure: The Percentage of Serosusceptible Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the B/Victoria Strain.
timeFrame: Day 0 and Day 28-35
measure: The Percentage of Seropositive Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the A/H1N1 Strain.
timeFrame: Day 0 and Day 28-35
measure: The Percentage of Seropositive Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the A/H3N2 Strain.
timeFrame: Day 0 and Day 28-35
measure: The Percentage of Seropositive Participants Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the B/Yamagata Strain.
timeFrame: Day 0 and Day 28-35
measure: The Percentage of Seropositive Subjects Experiencing Post Dose Strain-specific HAI Antibody Seroresponse to the B/Victoria Strain.
timeFrame: Day 0 and Day 28-35
measure: 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.
timeFrame: Day 28-35
measure: 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.
timeFrame: Day 28-35
measure: 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.
timeFrame: Day 28-35
measure: The Percentage of Serosusceptible Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the A/H1N1 Strain.
timeFrame: Day 28-35
measure: The Percentage of Serosusceptible Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the A/H3N2 Strain.
timeFrame: Day 28-35
measure: The Percentage of Serosusceptible Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the B/Yamagata Strain.
timeFrame: Day 28-35
measure: The Percentage of Serosusceptible Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the B/Victoria Strain.
timeFrame: Day 28-35
measure: The Percentage of Seropositive Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the A/H1N1 Strain.
timeFrame: Day 28-35
measure: The Percentage of Seropositive Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the A/H3N2 Strain.
timeFrame: Day 28-35
measure: The Percentage of Seropositive Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the B/Yamagata Strain.
timeFrame: Day 28-35
measure: The Percentage of Seropositive Participants Achieving a Post Dose Strain-specific HAI Antibody Titer ≥ 32 to the B/Victoria Strain.
timeFrame: Day 28-35
measure: The Percentage of Participants Experiencing Each Solicited Symptom From Administration of Investigational Product Through 14 Days Post Dose
timeFrame: Days 0-14 post dose
measure: The Percentage of Participants Reporting Any Adverse Event From Administration of Investigational Product Through 28 Days Post Dose
timeFrame: Days 0-28 post dose
measure: The Percentage of Participants Reporting Any Serious Adverse Event From Administration of Investigational Product Through 28 Days Post Dose
timeFrame: Days 0-28 post dose
measure: The Percentage of Participants Reporting Any Serious Adverse Event From Administration of Investigational Product Through 180 Days Post Dose
timeFrame: Days 0-180 post dose
measure: The Percentage of Participants Reporting New Onset Chronic Diseases From Administration of Investigational Product Through 180 Days Post Dose
timeFrame: Days 0-180 post dose
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Coastal Clinical Research, Inc.
state: Alabama
city: Sacramento
country: United States
facility: Benchmark Research
state: California
city: San Diego
country: United States
facility: California Research Foundation
state: California
city: San Francisco
country: United States
facility: Benchmark Research
state: California
city: Clearwater
country: United States
facility: Tampa Bay Medical Research, Inc.
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Stockbridge
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: Lenexa
country: United States
facility: Johnson County Clin-Trials
state: Kansas
city: Overland Park
country: United States
facility: Vince and Associates Clinical Research
state: Kansas
city: Metairie
country: United States
facility: Benchmark Research
state: Louisiana
city: Saint Louis
country: United States
facility: Sundance Clinical Research
state: Missouri
city: Omaha
country: United States
facility: Meridian Clinical Research, LLC
state: Nebraska
city: Endwell
country: United States
facility: Regional Clinical Research
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research Inc.
state: New York
city: Mount Pleasant
country: United States
facility: Palmetto Medical Research
state: South Carolina
city: Austin
country: United States
facility: Benchmark Research Austin
state: Texas
city: Fort Worth
country: United States
facility: Benchmark Research Ft. Worth
state: Texas
Study officials:
affiliation: MedImmune LLC
name: Joseph Sliman, M.D., MPH
role: STUDY_DIRECTOR
References:
citation: Sheldon EA, Jeanfreau R, Sliman JA, Charenkavanich S, Rousculp MD, Dubovsky F, Mallory RM. Immunogenicity of a quadrivalent Ann Arbor strain live attenuated influenza vaccine delivered using a blow-fill-seal device in adults: a randomized, active-controlled study*. Influenza Other Respir Viruses. 2013 Nov;7(6):1142-50. doi: 10.1111/irv.12027. Epub 2012 Oct 14.