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

• ClinicalTrials.gov Identifier: NCT01712984
• Recruitment Status: Completed
• First Posted: October 24, 2012
• Results First Posted: February 10, 2014
• Last Update Posted: May 7, 2015
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Influenza	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	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3360 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety Trial of Quadrivalent Influenza Vaccine Administered by Intradermal Route in Adult Subjects Aged 18 Through 64 Years
• Study Start Date: October 2012
• Actual Primary Completion Date: June 2013
• Actual Study Completion Date: October 2013

Arms and Interventions

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 Name: 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 Name: 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 Name: Fluzone® Intradermal

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: Day 28 post-vaccination ]
   Antibodies against the influenza vaccine virus antigens were measured using a Hemagglutination-inhibition (HAI) assay.
2. 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 [ Time Frame: Day 28 post-vaccination ]
   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).

Secondary Outcome Measures :

1. 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 [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ]
   Antibodies against the influenza vaccine virus antigens were measured using a Hemagglutination-inhibition (HAI) assay.
2. 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 [ Time Frame: Day 0 (pre-vaccination) and Day 28 post-vaccination ]
   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.
3. 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 [ Time Frame: Day 0 up to Day 7 post-vaccination ]
   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.

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, Alabama

Hoover, Alabama, United States, 35216

Huntsville, Alabama, United States, 35802

United States, Arizona

Chandler, Arizona, United States, 85224

Mesa, Arizona, United States, 85213

Phoenix, Arizona, United States, 85020

Tucson, Arizona, United States, 85704

United States, California

Chula Vista, California, United States, 91911

Sacramento, California, United States, 95816

San Diego, California, United States, 92103

United States, Connecticut

Milford, Connecticut, United States, 06460

United States, Florida

Coral Gables, Florida, United States, 33134

Melbourne, Florida, United States, 32935

Pinellas Park, Florida, United States, 33781

South Miami, Florida, United States, 33143

United States, Idaho

Boise, Idaho, United States, 83642

United States, Iowa

Iowa City, Iowa, United States, 52242

United States, Kansas

Overland Park, Kansas, United States, 66212

Wichita, Kansas, United States, 67207

United States, Missouri

Kansas City, Missouri, United States, 64114

Springfield, Missouri, United States, 65802

St. Louis, Missouri, United States, 63104

United States, Nebraska

Omaha, Nebraska, United States, 68134

United States, New York

Binghamton, New York, United States, 13901

Rochester, New York, United States, 14609

Rochester, New York, United States, 14621

United States, Pennsylvania

Allentown, Pennsylvania, United States, 18102

Bensalem, Pennsylvania, United States, 19020

United States, Rhode Island

Warwick, Rhode Island, United States, 02886

United States, South Carolina

Mt. Pleasant, South Carolina, United States, 29464

United States, South Dakota

Dakota Dunes, South Dakota, United States, 57049

United States, Texas

Austin, Texas, United States, 78745

Fort Worth, Texas, United States, 76107

Fort Worth, Texas, United States, 76135

San Angelo, Texas, United States, 76904

United States, Utah

Salt Lake City, Utah, United States, 84109

Salt Lake City, Utah, United States, 84121

West Jordan, Utah, United States, 84088

United States, Wisconsin

Marshfield, Wisconsin, United States, 54449

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director; Sanofi Pasteur Inc.

More Information

Additional Information:

Related Info 

Related Info 

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01712984
• Other Study ID Numbers: QID01; U1111-1124-8066 ( Other Identifier: WHO )
• First Posted: October 24, 2012
• Results First Posted: February 10, 2014
• Last Update Posted: May 7, 2015
• Last Verified: April 2015

Keywords provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):

Influenza; Fluzone® Intradermal vaccine; Influenza Virus Vaccine USP Quadrivalent; Influenza Virus Vaccine USP Trivalent Types A and B

Additional relevant MeSH terms:

Influenza, Human; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Fluconazole; Vaccines; Immunologic Factors; Physiological Effects of Drugs; Antifungal Agents; Anti-Infective Agents; 14-alpha Demethylase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Steroid Synthesis Inhibitors; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors