Safety and Immunogenicity of Flublok Quadrivalent vs IIV4 in Adults 18-49 Years of Age

Double-Blind, Randomized, Active-Controlled Comparison of the Immunogenicity and Safety of Flublok® Quadrivalent Versus IIV4 in Healthy, Medically Stable Adults 18-49 Years of Age

Randomized, double-blind trial of safety and immunogenicity of Flublok Quadrivalent versus Inactivated Influenza Vaccine (IIV4) in 1350 healthy, medically stable adults 18-49 years of age. Serum samples for Hemagglutinin Inhibition titers will be determined pre- and 28 days post-vaccination. Subjects will be followed for 6 months after vaccination for serious and/or medically-attended adverse events.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Flublok Quadrivalent; Biological: Inactivated Influenza Vaccine (IIV4)

Detailed Description

As the spectrum of influenza vaccines rapidly evolves to quadrivalent formulations with the intention of offering broader protection to include both lineages of influenza B strains, it is appropriate to transition Flublok from a trivalent to a quadrivalent formulation. The demonstration of non-inferior post-vaccination Hemagglutination Inhibition Assay (HAI) Geometric Mean Titers (GMTs) to antigens in the Flublok Quadrivalent formulation compared to those of the matching antigens in a US - approved IIV4 is intended to support licensure of Flublok Quadrivalent for the adult population for which Flublok trivalent is currently approved. The comparison of safety and reactogenicity of Flublok Quadrivalent to that of IIV4 is expected to confirm a similar safety profile.

• Study Type: Interventional
• Enrollment (Actual): 1350
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95816
      • Benchmark Research - Sacramento
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Benchmark Research
  • Nebraska
    • Bellevue, Nebraska, United States, 68005
      • Meridian Research
    • Omaha, Nebraska, United States, 68164
      • Meridian Clinical Research
  • South Dakota
    • Dakota Dunes, South Dakota, United States, 57049
      • Meridian Research
  • Texas
    • Austin, Texas, United States, 78705
      • Benchmark Reseach
    • Fort Worth, Texas, United States, 76135
      • Benchmark Research - Fort Worth

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ambulatory, in good health or medically stable
• Able to understand and comply with planned study procedures
• Provide written informed consent
• Negative urine pregnancy test within 24 hours prior to vaccination (women of child-bearing potential)

Exclusion Criteria:

• Prior serious or severe reaction to influenza vaccine
• Known contraindication to either study vaccine
• Receipt of any other influenza vaccine within 180 days prior to enrollment
• Plan to receive another licensed influenza or other vaccine during the duration of this study
• Receipt of any significant new diagnosis, medication (licensed or investigational), or licensed vaccine within 30 days prior to enrollment in this study
• Underlying disease or therapeutic intervention that might adversely affect the immune response
• Plans to participate in any investigation involving an investigational product during this study.
• Pregnant, lactating or planning to become pregnant within 30 days of study vaccine.
• Any clinical or social circumstance that in the opinion of the investigator could interfere with compliance with study procedures or interfere with the interpretation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Flublok Quadrivalent Influenza Vaccine; Intramuscular injection of vaccine containing 4 x 45µg (180µg total) of each recombinant hemagglutinin (rHA) derived from influenza A/H1N1 and A/H3N2 and two lineages of influenza B viruses identified for the season in which the trial is conducted in a total volume of 0.5 mL	Biological: Flublok Quadrivalent; Intramuscular injection of study vaccine
Active Comparator: Inactivated Influenza Vaccine (IIV4); Intramuscular injection of vaccine contains 4 x 15µg (60µg total) of HA derived from the same influenza A/H1N1 and A/H3N2 and influenza B strains in a total volume of 0.5mL.	Biological: Inactivated Influenza Vaccine (IIV4); Intramuscular injection of study vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroconversion to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine	Seroconversion is defined as: Either a pre vaccination titer < 10 (1/dil) and a post vaccination titer ≥ 40 (1/dil), or a pre vaccination titer ≥ 10 (1/dil) and a ≥ 4 fold increase in post vaccination titer at Day 28 after the final vaccination.	Day 28 after final vaccination
Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine	Immunogenicity will be evaluated prior to vaccination and at 28 days after vaccination using the hemagglutination inhibition (HAI) technique. For each influenza vaccine strain, pre and post vaccination geometric mean titers (GMTs) were calculated.	Day 0 and Day 28 after final vaccination

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Systemic and Injection Site Reactogenicity	Days 0-7
Number of Participants With Serious Adverse Events (SAEs) and Medically-attended Adverse Events (MAEs)	Six months post-vaccination

Collaborators and Investigators

• Sponsor: Protein Sciences Corporation
• Collaborators: Syneos Health; Department of Health and Human Services
• Investigators: Principal Investigator: William Seger, MD, Benchmark Research, Fort Worth, TX

Publications and helpful links

General Publications

• Dunkle LM, Izikson R, Patriarca PA, Goldenthal KL, Muse D, Cox MMJ. Randomized Comparison of Immunogenicity and Safety of Quadrivalent Recombinant Versus Inactivated Influenza Vaccine in Healthy Adults 18-49 Years of Age. J Infect Dis. 2017 Dec 5;216(10):1219-1226. doi: 10.1093/infdis/jix478.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: November 4, 2014
• First Submitted That Met QC Criteria: November 10, 2014
• First Posted (Estimate): November 14, 2014

Study Record Updates

• Last Update Posted (Estimate): October 27, 2016
• Last Update Submitted That Met QC Criteria: September 22, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: PSC16