Clinical trial NCT01712984: Study of Intradermal Quadrivalent Influenza Vaccine in Adults Aged 18 Through 64 Years
Official title: Immunogenicity and Safety Trial of Quadrivalent Influenza Vaccine Administered by Intradermal Route in Adult Subjects Aged 18 Through 64 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza
Keywords: Influenza
Fluzone® Intradermal vaccine
Influenza Virus Vaccine USP Quadrivalent
Influenza Virus Vaccine USP Trivalent Types A and B
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2012-10-24
Enrollment: 3360
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Day 28 post-vaccination
measure: 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
timeFrame: Day 28 post-vaccination
Secondary outcomes:
measure: 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
timeFrame: Day 0 (pre-vaccination) and Day 28 post-vaccination
measure: 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
timeFrame: Day 0 (pre-vaccination) and Day 28 post-vaccination
measure: 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
timeFrame: Day 0 up to Day 7 post-vaccination
Other outcomes:
Locations:
city: Hoover
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Chandler
country: United States
state: Arizona
city: Mesa
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Chula Vista
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: Milford
country: United States
state: Connecticut
city: Coral Gables
country: United States
state: Florida
city: Melbourne
country: United States
state: Florida
city: Pinellas Park
country: United States
state: Florida
city: South Miami
country: United States
state: Florida
city: Boise
country: United States
state: Idaho
city: Iowa City
country: United States
state: Iowa
city: Overland Park
country: United States
state: Kansas
city: Wichita
country: United States
state: Kansas
city: Kansas City
country: United States
state: Missouri
city: Springfield
country: United States
state: Missouri
city: St. Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Binghamton
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Allentown
country: United States
state: Pennsylvania
city: Bensalem
country: United States
state: Pennsylvania
city: Warwick
country: United States
state: Rhode Island
city: Mt. Pleasant
country: United States
state: South Carolina
city: Dakota Dunes
country: United States
state: South Dakota
city: Austin
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: San Angelo
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: West Jordan
country: United States
state: Utah
city: Marshfield
country: United States
state: Wisconsin
Study officials:
affiliation: Sanofi Pasteur Inc.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.