FLU-VACS Comparative Study in Adults

Comparative Study of Influenza Vaccines in Adults - FLU-VACS

The purpose of this study is to compare 2 licensed flu vaccines to each other and to placebo (inactive substance). The study will be conducted among healthy adult participants aged 18-49 years and is expected to last 3 years. During year 1, participants will be assigned to receive 1 of the 2 licensed flu vaccines or placebo, given as either nasal spray (live-attenuated vaccine or placebo) or injection (inactivated vaccine or placebo). Participants will receive the same assigned vaccine or placebo during year 2. During year 3, participants will be followed, but will not receive flu vaccine. Each year blood samples will be collected before and 1 month after each vaccination and at the end of each flu season in order to measure how the body responds to the vaccine and how well participants were protected from the flu. During the flu season, participants with flu-like illness will provide information on symptoms and provide a throat swab to test for virus identification.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Other: Placebo; Other: Placebo; Biological: Cold-adapted live attenuated influenza virus vaccine, trivalent; Biological: Trivalent inactivated influenza vaccine; Biological: Trivalent inactivated influenza vaccine

Detailed Description

Influenza occurs on an annual basis, producing significant mortality in most years, mainly in those with underlying conditions and those at extremes of age. This study is a placebo-controlled trial to examine efficacies of the live attenuated and inactivated influenza vaccines, and immune correlates of protection; the study will take place in Michigan over a three year period, and will target adults aged 18-49 years. Both vaccine preparations are licensed for this age group. In the first year, participants will be randomly assigned to receive one of the two licensed vaccines or placebo. In the second year, participant receipt of vaccine (updated according to national recommendations) or placebo will continue as assigned in the first year for returning participants, and new enrollees will be randomly assigned to intervention. In the third year, when duration of immunity will be evaluated, no interventions will be given. In all study years, blood specimens for serologic studies and specimens for virus identification will be collected and a number of laboratory studies will be performed so that it will be possible to achieve the study's objectives. The primary annual study outcome for efficacy is the proportion of subjects with laboratory-confirmed symptomatic influenza A or B illness, defined as influenza virus isolated in tissue culture from a throat swab obtained from a participant during an episode of illness meeting the influenza case definition that is confirmed as influenza by fluorescent antibody or polymerase chain reaction (PCR) techniques; or serologic confirmation of influenza infection in a participant with an episode of illness meeting the influenza case definition, specifically a 4-fold rise in hemagglutinin inhibition assay (HAI) antibody titer to a circulating influenza strain between post-vaccination (pre-season) and post-season paired sera. The influenza case definition is illness with at least one respiratory symptom (cough or nasal congestion) and at least one constitutional symptom (fever or feverishness, chills or body aches). Subjects will be evaluated for serious adverse events throughout each annual study period. Annually, the proportion of participants with local reactions during the first seven days or any adverse reactions during the first thirty days after vaccine receipt will be compared with recipients of placebo.

• Study Type: Interventional
• Enrollment (Actual): 2349
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-2029
      • University of Michigan
    • Ann Arbor, Michigan, United States, 48103
      • Ann Arbor West
    • Kalamazoo, Michigan, United States, 49008
      • Western Michigan University Health Services
    • Livonia, Michigan, United States, 48150
      • Livonia East
    • Mt. Pleasant, Michigan, United States, 48859
      • Central Michigan University Health Services
    • Ypsilanti, Michigan, United States, 48197
      • Eastern Michigan University Health Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Persons must be adult men and women aged 18-49 years.
• Persons must be able and willing to provide informed consent.
• Persons must expect to reside in the study area during the entire study period and be interested in participating each year.
• Persons must be willing to receive the licensed live-attenuated vaccine (FluMist) or placebo given as a nasal spray, or the licensed inactivated influenza vaccine (Fluzone or Fluvirin) or placebo given as an intramuscular injection.
• Persons must be willing to provide multiple blood specimens collected by venipuncture each year they are in the study. During each of the first two years of study, blood specimens will be collected three times - at the enrollment visit (immediately prior to administration of vaccine or placebo), at the first follow-up visit 3-5 weeks later, and at the end of the influenza season visit (approximately 4-6 months later); during the third year of the study, blood specimens will be collected twice only, at visits before and after the influenza season.
• Persons must be willing to notify study personnel in the event of influenza-like illness, to provide information on illness symptoms, and to permit collection of a throat culture (swab) specimen for laboratory studies.
• Persons must be willing to not receive an influenza vaccine while participating - other than that (influenza vaccine or placebo) received as study medication.

Exclusion Criteria:

• Persons with any health condition for which the inactivated vaccine is recommended (Advisory Committee on Immunization Practices - ACIP) including: chronic diseases of the pulmonary or cardiovascular systems (including asthma); chronic metabolic diseases (including diabetes); renal dysfunction; hemoglobinopathies; immune deficiency disease (including HIV infection) or on-going immunosuppressive therapy.
• Persons who are currently pregnant, nursing mothers or planning a pregnancy within one month of vaccination.
• Persons with hypersensitivity to egg, egg protein, thimerosal (a preservative) or the antibiotic Gentamicin (also know as Garamycin).
• Persons who have had a prior serious reaction to influenza vaccine, or ever had Guillain-Barre syndrome.
• Persons who are living in a household with or have direction occupational contact with immunosuppressed individuals (including health care workers with direct patient contact).
• Persons who have received an influenza vaccine for the influenza season in which they are to be first enrolled or those who plan to receive an influenza vaccine during their participation in the study - other than that (influenza vaccine or placebo) received as study medication.
• Persons who have received any other vaccine within one week prior to enrollment (may delay enrollment).
• Persons who have had a respiratory illness or illness with fever within 3 days of study enrollment (may delay enrollment).
• Persons who are participating in another research study involving any study medications (medicines or vaccines).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group 4: Placebo: Intramuscular; N=165 subjects administered placebo intramuscularly.	Other: Placebo; Physiological saline administered as an intramuscular injection.; Other: Placebo; Normal allantoic fluid administered annually as an internasal spray.
Placebo Comparator: Group 3: Placebo: Nasal; N=165 subjects administered placebo intranasally.	Other: Placebo; Physiological saline administered as an intramuscular injection.; Other: Placebo; Normal allantoic fluid administered annually as an internasal spray.
Experimental: Group 1: FluMist™; N=825 subjects administered live attenuated vaccine intranasally.	Biological: Cold-adapted live attenuated influenza virus vaccine, trivalent; Live-attenuated influenza vaccine; single annual dose administered as an intranasal spray.
Experimental: Group 2: Fluzone®/Fluvirin; N=825 subjects administered inactivated vaccine intramuscularly.	Biological: Trivalent inactivated influenza vaccine; Inactivated influenza vaccine; single annual dose administered as an intramuscular injection..; Biological: Trivalent inactivated influenza vaccine; Inactivated influenza vaccine; single annual dose administered as an intramuscular injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The appearance among patients of symptomatic laboratory-confirmed influenza.	Influenza season Nov-Apr. Within 72 hours of illness onset throat swab specimens will be obtained from participants with influenza like illness (ILI).

Secondary Outcome Measures

Outcome Measure	Time Frame
Any measurable increase in antibody titers, and the proportion with antibody levels considered protective.	Annual enrollment, post vaccination Oct-Jan, and post season Apr-May.

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

General Publications

• Ohmit SE, Victor JC, Rotthoff JR, Teich ER, Truscon RK, Baum LL, Rangarajan B, Newton DW, Boulton ML, Monto AS. Prevention of antigenically drifted influenza by inactivated and live attenuated vaccines. N Engl J Med. 2006 Dec 14;355(24):2513-22. doi: 10.1056/NEJMoa061850.
• Ohmit SE, Victor JC, Teich ER, Truscon RK, Rotthoff JR, Newton DW, Campbell SA, Boulton ML, Monto AS. Prevention of symptomatic seasonal influenza in 2005-2006 by inactivated and live attenuated vaccines. J Infect Dis. 2008 Aug 1;198(3):312-7. doi: 10.1086/589885.
• Petrie JG, Ohmit SE, Johnson E, Cross RT, Monto AS. Efficacy studies of influenza vaccines: effect of end points used and characteristics of vaccine failures. J Infect Dis. 2011 May 1;203(9):1309-15. doi: 10.1093/infdis/jir015. Epub 2011 Mar 4.

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): July 1, 2007
• Study Completion (Actual): July 1, 2007

Study Registration Dates

• First Submitted: August 19, 2005
• First Submitted That Met QC Criteria: August 19, 2005
• First Posted (Estimate): August 23, 2005

Study Record Updates

• Last Update Posted (Estimate): December 5, 2014
• Last Update Submitted That Met QC Criteria: December 4, 2014
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: FLU-VACS, influenza, vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 04-060; IRBMed# 2004-0334