Study of Intradermal Quadrivalent Influenza Vaccine in Adults Aged 18 Through 64 Years

Immunogenicity and Safety Trial of Quadrivalent Influenza Vaccine Administered by Intradermal Route in Adult Subjects Aged 18 Through 64 Years

The aim of the study is to demonstrate safety and immunogenicity of the quadrivalent influenza intradermal (QIV-ID) vaccine compared to the trivalent influenza vaccine (TIV) containing the B strain from the primary (Yamagata) lineage (TIV-ID1) and the trivalent influenza vaccine containing B strain from the alternate (Victoria) lineage (TIV-ID2) vaccines in producing protection against four strains of influenza virus.

Primary Objective:

• To demonstrate that QIV-ID induces an immune response (as assessed by hemagglutination inhibition (HAI) geometric mean titers (GMTs) and seroconversion rates) that is non-inferior to responses induced by TIV-ID1 and TIV-ID2 for the 4 virus strains at 28 days post-vaccination.

Secondary Objectives:

• To demonstrate that each B strain in QIV-ID induces an immune response (as assessed by HAI GMTs and seroconversion rates) that is superior to the response induced by the TIV-ID that does not contain the corresponding B strain.
• To describe the rate of post-vaccination seroprotection induced by QIV-ID and TIV-ID.
• To describe post-vaccination immunogenicity stratified by age (18-49 years and 50-64 years), race, ethnicity, gender, previous vaccination status, and baseline seropositivity status.
• To describe the safety profile for subjects who receive QIV-ID and TIV-ID.

Observational Objectives:

• To demonstrate non-inferiority of QIV-ID compared to TIV-ID in terms of all Grade 2 or Grade 3 solicited systemic reactions combined
• To demonstrate non-inferiority of QIV-ID compared to TIV-ID in terms of all Grade 3 solicited injection site reactions combined.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Influenza Virus Vaccine USP Quadrivalent, (Zonal Purified Subvirion) 2012 2013 Formulation; Biological: Influenza Virus Vaccine USP Trivalent Types A and B (Zonal Purified Subvirion) Fluzone® Intradermal; Biological: Influenza Virus Vaccine USP Trivalent Types A and B (Zonal Purified Subvirion) Fluzone Intradermal

Detailed Description

All participants will receive a single dose of their assigned vaccine on Day 0. A subset of the participants will be assessed for immunologic response on Day 0 before vaccination and Day 28 after vaccination. All subjects will be monitored for safety for up to 6 months after vaccination.

• Study Type: Interventional
• Enrollment (Actual): 3360
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Hoover, Alabama, United States, 35216
    • Huntsville, Alabama, United States, 35802
  • Arizona
    • Chandler, Arizona, United States, 85224
    • Mesa, Arizona, United States, 85213
    • Phoenix, Arizona, United States, 85020
    • Tucson, Arizona, United States, 85704
  • California
    • Chula Vista, California, United States, 91911
    • Sacramento, California, United States, 95816
    • San Diego, California, United States, 92103
  • Connecticut
    • Milford, Connecticut, United States, 06460
  • Florida
    • Coral Gables, Florida, United States, 33134
    • Melbourne, Florida, United States, 32935
    • Pinellas Park, Florida, United States, 33781
    • South Miami, Florida, United States, 33143
  • Idaho
    • Boise, Idaho, United States, 83642
  • Iowa
    • Iowa City, Iowa, United States, 52242
  • Kansas
    • Overland Park, Kansas, United States, 66212
    • Wichita, Kansas, United States, 67207
  • Missouri
    • Kansas City, Missouri, United States, 64114
    • Springfield, Missouri, United States, 65802
    • St. Louis, Missouri, United States, 63104
  • Nebraska
    • Omaha, Nebraska, United States, 68134
  • New York
    • Binghamton, New York, United States, 13901
    • Rochester, New York, United States, 14621
    • Rochester, New York, United States, 14609
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18102
    • Bensalem, Pennsylvania, United States, 19020
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
  • South Carolina
    • Mt. Pleasant, South Carolina, United States, 29464
  • South Dakota
    • Dakota Dunes, South Dakota, United States, 57049
  • Texas
    • Austin, Texas, United States, 78745
    • Fort Worth, Texas, United States, 76107
    • Fort Worth, Texas, United States, 76135
    • San Angelo, Texas, United States, 76904
  • Utah
    • Salt Lake City, Utah, United States, 84121
    • Salt Lake City, Utah, United States, 84109
    • West Jordan, Utah, United States, 84088
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18 through 64 years on the day of inclusion
• Informed consent form (ICF) has been signed and dated
• Able to attend all scheduled visits and to comply with all trial procedures. Exclusion Criteria:
• Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination and until at least 4 weeks after vaccination)
• Participation at the time of trial enrollment (or in the 4 weeks preceding the trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure
• Receipt of any vaccine in the 4 weeks preceding the trial vaccination or planned receipt of any vaccine in the 4 weeks following trial vaccination
• Vaccination against influenza in the past 6 months
• Receipt of immune globulins, blood or blood-derived products in the past 3 months
• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances
• History of thrombocytopenia
• Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
• Current alcohol abuse or drug addiction
• Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
• Identified as an Investigator or employee of the Investigator or trial center with direct involvement in the proposed trial, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed trial
• Personal or family history of Guillain-Barré Syndrome
• Neoplastic disease or any hematologic malignancy (except localized skin or prostate cancer that is stable at the time of vaccination in the absence of therapy, and subjects who have a history of neoplastic disease and who have been disease free for ≥ 5 years.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QIV ID Vaccine Group; Participants will receive the intradermal quadrivalent influenza vaccine	Biological: Influenza Virus Vaccine USP Quadrivalent, (Zonal Purified Subvirion) 2012 2013 Formulation; 0.1mL, Intradermal; Other Names: QIV ID
Active Comparator: TIV ID1 Vaccine Group; Participants will receive the trivalent influenza vaccine containing the B strain from the primary (Yamagata) lineage	Biological: Influenza Virus Vaccine USP Trivalent Types A and B (Zonal Purified Subvirion) Fluzone® Intradermal; 0.1mL, Intradermal; Other Names: Fluzone® Intradermal
Active Comparator: TIV ID2 Group; Participants will receive the intradermal trivalent influenza vaccine containing B strain from the alternate (Victoria) lineage	Biological: Influenza Virus Vaccine USP Trivalent Types A and B (Zonal Purified Subvirion) Fluzone Intradermal; 0.1mL, Intradermal; Other Names: Fluzone® Intradermal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers Against the Influenza Virus Antigens Following Vaccination With Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered by Intradermal Route	Antibodies against the influenza vaccine virus antigens were measured using a Hemagglutination-inhibition (HAI) assay.	Day 28 post-vaccination
Number of Participants With Seroconversion to Influenza Virus Vaccine Antigens Following Vaccination With Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered by Intradermal Route	Antibodies against the influenza vaccine virus antigens were measured using a Hemagglutination-inhibition (HAI) assay. Seroconversion was defined as titer< 10 (1/dil) on Day 0 and post injection titer ≥ 40 (1/dil) on Day 28, or titer ≥10 (1/dil) on Day 0 and a ≥4 fold increase in titer (1/dil) on Day 28).	Day 28 post-vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers Against the Influenza Virus Antigens Before and Following Vaccination With Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered by Intradermal Route	Antibodies against the influenza vaccine virus antigens were measured using a Hemagglutination-inhibition (HAI) assay.	Day 0 (pre-vaccination) and Day 28 post-vaccination
Number of Participants With Seroprotection Against Influenza Vaccine Antigens Before (Baseline) and Following Vaccination With Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered by Intradermal Route	Antibodies against the influenza vaccine virus antigens were measured using a Hemagglutination-inhibition (HAI) assay. Seroprotection was defined as titer ≥ 40 [1/dil] at baseline and 28 days after vaccination.	Day 0 (pre-vaccination) and Day 28 post-vaccination
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered by Intradermal Route	Solicited injection site: Pain, Erythema, Swelling, Induration, Ecchymosis, and Pruritus; Solicited systemic reactions: Fever (Temperature), Headache, Malaise, Myalgia, and Shivering. Grade 3 injection site: Pain and Pruritus Significant, prevents daily activity; Erythema, Swelling, Induration, and Ecchymosis >100 mm. Grade 3 systemic reactions: Fever ≥39˚C; Headache, Malaise, Myalgia, and Shivering Significant preventing daily activity.	Day 0 up to Day 7 post-vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Gorse GJ, Falsey AR, Ozol-Godfrey A, Landolfi V, Tsang PH. Safety and immunogenicity of a quadrivalent intradermal influenza vaccine in adults. Vaccine. 2015 Feb 25;33(9):1151-9. doi: 10.1016/j.vaccine.2015.01.025. Epub 2015 Jan 19.
• Small RD, Ozol-Godfrey A, Yan L. On the use of nonparametric tests for comparing immunological Reverse Cumulative distribution curves (RCDCs). Vaccine. 2019 Oct 16;37(44):6737-6742. doi: 10.1016/j.vaccine.2019.09.007. Epub 2019 Sep 16.

Helpful Links

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Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: October 22, 2012
• First Submitted That Met QC Criteria: October 22, 2012
• First Posted (Estimate): October 24, 2012

Study Record Updates

• Last Update Posted (Estimate): May 7, 2015
• Last Update Submitted That Met QC Criteria: April 20, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Influenza; Fluzone® Intradermal vaccine; Influenza Virus Vaccine USP Quadrivalent; Influenza Virus Vaccine USP Trivalent Types A and B
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Immunologic Factors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Vaccines; Fluconazole
• Other Study ID Numbers: QID01; U1111-1124-8066 (Other Identifier: WHO)