Randomized Influenza Vaccine Evaluation of Immune Response (RIVER)

Randomized Open-Label Trial to Compare Immunogenicity of Egg-Based and Non-Egg Based Quadrivalent Influenza Vaccines Among Adults 18-64 Years of Age (US Flu Vaccine Effectiveness Serologic Study, 2018-19 and 2019-20)

Licensed influenza vaccines are manufactured with a variety of technologies. The majority are split, inactivated vaccines derived from egg-adapted, high growth reassortant viruses. Two US licensed products do not use egg-adapted viruses: Flucelvax (mammalian cell culture) and FluBlok (recombinant). There is increasing evidence that egg propagation induces virus mutations that impair the immune responses to circulating viruses. However, the impact of egg-propagation on clinical vaccine effectiveness is uncertain, and there is no preferential recommendation for any specific influenza vaccine product or technology. A direct comparison of serologic response to egg based and non-egg based vaccines in adults has not been performed. This randomized trial will compare serologic responses to the egg- and non-egg A(H3N2) vaccine component. The study cohort will be followed for two influenza seasons to evaluate sequential vaccination effects on immune response.

Study Overview

• Status: Active, not recruiting
• Conditions: Influenza
• Intervention / Treatment: Biological: Recombinant; Biological: Cell-culture; Biological: Standard IIV4

• Study Type: Interventional
• Enrollment (Actual): 366
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic - Marshfield Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 18-64 years
• Marshfield Clinic patients living in or around Marshfield, Wisconsin since July 2015
• Willing and able to give informed consent and comply with study requirements

Exclusion Criteria:

• Receipt of 2018-19 influenza vaccine prior to study enrollment
• Known to be pregnant at the time of enrollment
• Current participation or plans to participate in another clinical trial involving an experimental agent
• Presence of a contraindication to influenza vaccination
• Plans to relocate outside the geographic location in the next two years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Recombinant (RIV4) Influenza Vaccine; A single dose of licensed recombinant influenza vaccine will be given in each of two influenza seasons - one in 2018-19 and a second in 2019-20.	Biological: Recombinant; Influenza vaccine that uses a hemagglutinin protein manufactured in insect cells with a baculovirus vector; Other Names: FluBlok Quadrivalent
Experimental: Cell-culture (ccIIV4) Influenza Vaccine; A single dose of licensed cell-culture influenza vaccine will be given in each of two influenza seasons - one in 2018-19 and a second in 2019-20	Biological: Cell-culture; inactivated influenza vaccine manufactured using mammalian cell lines; current vaccine uses a cell-propagated H3N2 strain.; Other Names: Flucelvax Quadrivalent
Active Comparator: Standard (IIV4) Influenza Vaccine; A single dose of licensed standard influenza vaccine will be given in each of two influenza seasons - one in 2018-19 and a second in 2019-20.	Biological: Standard IIV4; Standard inactivated influenza vaccine; Other Names: Flulaval Quadrivalent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-vaccination titer	geometric mean titers (as measured by microneutralization) to cell-grown A(H3N2) vaccine reference virus	28 days

Collaborators and Investigators

• Sponsor: Marshfield Clinic Research Foundation
• Collaborators: Centers for Disease Control and Prevention

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2018
• Primary Completion (Actual): March 18, 2020
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: July 16, 2018
• First Submitted That Met QC Criteria: July 16, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): April 24, 2023
• Last Update Submitted That Met QC Criteria: April 21, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: influenza vaccine; adults; Immune response
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: MCL10218

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No