Clinical trial NCT00860067: A Study to Evaluate the Immunogenicity of Quadrivalent LAIV in Adults 18 to 49 Years of Age
Official title: A Randomized, Double-Blind, Active Controlled Study to Evaluate the Immunogenicity of MEDI3250 in Adults 18 to 49 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Healthy or Stable Underlying Chronic Medical Condition
Keywords: influenza, FluMist, adults, vaccine
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2009-03-11
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 objective of this study was to show that quadrivalent live attenuated influenza vaccine (Q/LAIV; MEDI3250) produced antibody levels similar to those produced by the commercial vaccine, FluMist.

Detailed description: This randomized, double-blind, active controlled, multicenter study enrolled 1,800 subjects who were 18 to 49 years of age. Subjects were randomized by site in a 4:1:1 fashion to receive a single dose of Q/LAIV, trivalent FluMist containing an influenza B strain from the Yamagata lineage (FluMist/B/Yamagata), or trivalent FluMist containing an influenza B strain from the Victoria lineage (FluMist/B/Victoria). The study was conducted at multiple sites in the USA in the influenza off-season.

Eligibility criteria: Inclusion Criteria:

* Male or female age 18 to 49 years, inclusive, on the day of randomization (reached his or her eighteenth year birthday but not yet reached his or her 50th year birthday) at the time of the dose of blinded investigational product
* Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
* Females of child-bearing potential, (ie, unless surgically sterile \[eg, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy\], had a sterile male partner, was at least 1 year post-menopausal, or practiced 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, or use of a condom with spermicide by the sexual partner) 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 subject must also have had a negative urine or blood pregnancy test at screening and, if screening and Day 0 did not occur on the same day, on the day of vaccination prior to randomization. Investigator judgment was required to assess a female subject's capability of pregnancy.
* Healthy by medical history and physical examination OR presence of stable underlying chronic medical condition for which hospitalization was not required in the previous year
* Able to complete follow-up period of 180 days post dose of vaccine as required by the protocol
* Subject available by telephone
* 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°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 or chronic medications 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 might have compromised the safety of the subject in the study
* Current or expected receipt of immunosuppressive medications (inhaled and topical corticosteroids were permitted) including corticosteroids (≥ 20 mg/day of prednisone equivalent given daily or on alternate days for ≥ 14 days) within a 30-day window around dose of investigational product Note: topical corticosteroids for uncomplicated dermatitis were permitted according to the judgment of the investigator; topical calcineurin inhibitors were permitted 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 or standard vaccine within 30 days before the dose of investigational product in this study through 30 days after the dose of investigational product (use of licensed agents for indications not listed in the package insert was permitted)
* 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
* 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 dose of investigational product or anticipated use within 30 days after vaccination
* Known or suspected mitochondrial encephalomyopathy
* Lactating woman
* History of alcohol or drug abuse that, in the opinion of the investigator, would have affected the subject's safety or compliance with study
* Any condition that, in the opinion of the investigator, would have interfered with evaluation of the investigational product or interpretation of subject safety or study results
* Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals

Primary outcomes:
measure: The 4 Post-dose Strain-specific Serum Hemagglutination Inhibition (HAI) Antibody Geometric Mean Titers (GMT) in the Q/LAIV (MEDI3250) Arm Are Noninferior to Those in the Comparator FluMist Group.
timeFrame: Day 28-35
Secondary outcomes:
measure: The Number of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Experience Strain-specific Seroresponse Post Dose.
timeFrame: Day 0 and Day 28-35
measure: The Number of Serosusceptible Participants Within Each Treatment Arm Who Experience A/H1N1 Strain-specific Seroresponse Post Dose.
timeFrame: Day 0 and Day 28-35
measure: The Number of Serosusceptible Participants Within Each Treatment Arm Who Experience A/H3N2 Strain-specific Seroresponse Post Dose.
timeFrame: Day 0 and Day 28-35
measure: The Number of Serosusceptible Participants Within Each Treatment Arm Who Experience B/Yamagata Strain-specific Seroresponse Post Dose.
timeFrame: Day 0 and Day 28-35
measure: The Number of Serosusceptible Participants Within Each Treatment Arm Who Experience B/Victoria Strain-specific Seroresponse Post Dose.
timeFrame: Day 0 and Day 28-35
measure: The Number of Seropositive Participants Within Each Treatment Arm Who Experience A/H1N1 Strain-specific Seroresponse Post Dose.
timeFrame: Day 0 and Day 28-35
measure: The Number of Seropositive Participants Within Each Treatment Arm Who Experience A/H3N2 Strain-specific Seroresponse Post Dose.
timeFrame: Day 0 and Day 28-35
measure: The Number of Seropositive Participants Within Each Treatment Arm Who Experience B/Yamagata Strain-specific Seroresponse Post Dose.
timeFrame: Day 0 and Day 28-35
measure: The Number of Seropositive Participants Within Each Treatment Arm Who Experience B/Victoria Strain-specific Seroresponse Post Dose.
timeFrame: Day 0 and Day 28-35
measure: The Number of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Achieved a Strain-specific HAI Antibody Titer ≥ 32 Post Dose.
timeFrame: Day 28-35
measure: The Number of Serosusceptible Participants Within Each Treatment Arm Who Achieved a A/H1N1 Strain-specific HAI Antibody Titer ≥ 32 Post Dose.
timeFrame: Day 28-35
measure: The Number of Serosusceptible Participants Within Each Treatment Arm Who Achieved a A/H3N2 Strain-specific HAI Antibody Titer ≥ 32 Post Dose.
timeFrame: Day 28-35
measure: The Number of Serosusceptible Participants Within Each Treatment Arm Who Achieved a B/Yamagata Strain-specific HAI Antibody Titer ≥ 32 Post Dose.
timeFrame: Day 28-35
measure: The Number of Serosusceptible Participants Within Each Treatment Arm Who Achieved a B/Victoria Strain-specific HAI Antibody Titer ≥ 32 Post Dose.
timeFrame: Day 28-35
measure: The Number of Seropositive Participants Within Each Treatment Arm Who Achieved a A/H1N1 Strain-specific HAI Antibody Titer ≥ 32 Post Dose.
timeFrame: Day 28-35
measure: The Number of Seropositive Participants Within Each Treatment Arm Who Achieved a A/H3N2 Strain-specific HAI Antibody Titer ≥ 32 Post Dose.
timeFrame: Day 28-35
measure: The Number of Seropositive Participants Within Each Treatment Arm Who Achieved a B/Yamagata Strain-specific HAI Antibody Titer ≥ 32 Post Dose.
timeFrame: Day 28-35
measure: The Number of Seropositive Participants Within Each Treatment Arm Who Achieved a B/Victoria Strain-specific HAI Antibody Titer ≥ 32 Post Dose.
timeFrame: Day 28-35
measure: The Number of Participants Experiencing Each Solicited Symptom From Administration of Investigational Product Through 14 Days Post Vaccination
timeFrame: Days 0-14
measure: The Number of Participants Reporting Any Adverse Event From Administration of Investigational Product Through 28 Days Post Vaccination
timeFrame: Days 0-28 post vaccination
measure: Number of Participants Reporting Any Serious Adverse Event From Administration of Investigational Product Through 28 Days Post Vaccination
timeFrame: Days 0-28 post vaccination
measure: Number of Participants Reporting Any Serious Adverse Event From Administration of Investigational Product Through 180 Days Post Vaccination
timeFrame: Days 0-180 post vaccination
measure: Number of Participants Reporting New Onset Chronic Diseases From Administration of Investigational Product Through 180 Days Post Vaccination
timeFrame: Days 0-180 post vaccination
Other outcomes:
Locations:
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: Deland
country: United States
facility: University Clinical Research-Deland, LLC
state: Florida
city: Miami
country: United States
facility: Pharmax Research Clinic, Inc
state: Florida
city: Pembroke Pines
country: United States
facility: University Clinical Research, Inc
state: Florida
city: South Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Stockbridge
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: Overland Park
country: United States
facility: Vince and Associates Clinical Research
state: Kansas
city: Bardstown
country: United States
facility: Kentucky Pediatric / Adult Research
state: Kentucky
city: Kansas City
country: United States
facility: The Center for Pharmaceutical Research, PC
state: Missouri
city: St. Louis
country: United States
facility: Sundance Clinical Research
state: Missouri
city: Omaha
country: United States
facility: Meridian Clinical Research, LLC
state: Nebraska
city: Rochester
country: United States
facility: Rochester Clinical Research, Inc.
state: New York
city: Nashville
country: United States
facility: Clinical Research Associates, Inc
state: Tennessee
city: Austin
country: United States
facility: Benchmark Research
state: Texas
city: Ft. Worth
country: United States
facility: Benchmark Research
state: Texas
city: West Jordan
country: United States
facility: Advanced Clinical Research
state: Utah
Study officials:
affiliation: MedImmune LLC
name: Judith Falloon, M.D.
role: STUDY_DIRECTOR
References:
citation: Block SL, Yi T, Sheldon E, Dubovsky F, Falloon J. A randomized, double-blind noninferiority study of quadrivalent live attenuated influenza vaccine in adults. Vaccine. 2011 Nov 21;29(50):9391-7. doi: 10.1016/j.vaccine.2011.09.109. Epub 2011 Oct 6.