Study of Inactivated, Split-Virion Influenza Vaccine and Standard Fluzone® Vaccine in Adult and Elderly Subjects

Study Overview
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Brief Summary
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The present formulations are being developed for further study in the elderly population in order to generate additional supporting data. Primary Objective: To demonstrate non-inferiority of post-vaccination immunogenicity of subjects who received either 1 of the 2 investigational formulations of a trivalent inactivated vaccine (TIV) compared to that of the standard Fluzone® in elderly subjects. Secondary Objectives: Immunogenicity To describe the immunogenicity in subjects receiving investigational Fluzone and standard Fluzone®. Safety: To evaluate and describe the safety profile of investigational Fluzone in terms of solicited- and unsolicited adverse events and serious adverse events post-vaccination.

Official Title
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Immunogenicity and Safety of Two Dosages of the Split, Inactivated, Trivalent Influenza Vaccine Administered by Intradermal Route in the Elderly Compared With Standard Fluzone® in Adults and Elderly Subjects.

Conditions
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Influenza, Myxovirus Infection

Intervention / Treatment
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* Biological: Split, Inactivated, Trivalent Influenza Vaccine (Intradermal Formulation 1)
* Biological: Split, Inactivated, Trivalent Influenza Vaccine (Intradermal Formulation 2)
* Biological: Split, Inactivated, Trivalent Influenza Vaccine (Standard dose)
* Biological: Split, Inactivated, Trivalent Influenza Vaccine (High-dose)
* Biological: Split, Inactivated, Trivalent Influenza Vaccine (Standard dose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 65 years or aged 18 to 49 years on the day of vaccination. Informed consent form signed. Medically stable (Subjects may have underlying illnesses such as hypertension, diabetes, ischemic heart disease or hypothyroidism, as long as their symptoms/signs are controlled. If they are on medication for a condition, the medication dose must have been stable for at least 3 weeks preceding vaccination. Able to attend all scheduled visits and to comply with all trial procedures. For a woman of child-bearing potential, avoid becoming pregnant (use of an effective method of contraception or abstinence) for at least 4 weeks prior to vaccination, until at least 4 weeks after vaccination Exclusion Criteria: Known systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to the standard-dose Fluzone® vaccine or to a vaccine containing any of the same substances. Known or suspected congenital or acquired immunodeficiency, hepatitis B (HBsAg) or hepatitis C infection or seropositivity immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term systemic corticosteroids therapy For a woman of child-bearing potential, known pregnancy or positive urine pregnancy test. Breast feeding woman. 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, as well as subjects who have a history of neoplastic disease and who have been disease free for ≥ 5 years). Current use of alcohol or recreational drugs that in the opinion of the Investigator may interfere with the subject's ability to comply with trial procedures. Receipt of blood or blood-derived products in the past 3 months that might interfere with the assessment of immune response. Vaccination against influenza in the past 6 months. Any vaccination in the 4 weeks preceding the trial vaccination. Planned receipt of any other vaccine in the four weeks following the trial vaccination. Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding trial vaccination. Planned participation in another clinical trial during the present trial period. Note: Concomitant participation in an observational trial (not involving drugs, vaccines, or medical devices) is acceptable. Known thrombocytopenia or bleeding disorder or anticoagulants in the 3 weeks preceding inclusion contraindicating intramuscular vaccination. Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the investigator Personal or family history of Guillain-Barré Syndrome. Known current human immunodeficiency virus (HIV), hepatitis B (HBsAg) or hepatitis C infection or seropositivity. Subject deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent. An acute febrile illness [oral temperature ≥ 99.5°F (≥ 37.5°C)] within 24 hours prior to vaccination. If this exists, vaccination will be deferred until the participant becomes afebrile. Signs and symptoms of an acute infectious respiratory illness. If this exists, vaccination will be deferred until the symptoms resolve. The use of an antibiotics therapy within 72 hours preceding the trial vaccination. If this exists, vaccination will be deferred until at least 72 hours after the last antibiotics therapy. Receipt of any allergy shots in the 7-day period prior to enrollment (vaccination), or scheduled to receive any allergy shots in the 7-day period after enrollment (vaccination). Subjects should be enrolled in the trial only if their allergy shots are given on a stable schedule outside the 7-day periods pre- and post-vaccination.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Influenza Virus Vaccine Formulation 1<br>Influenza Virus Vaccine Formulation 1 | Biological: Split, Inactivated, Trivalent Influenza Vaccine (Intradermal Formulation 1)<br>* 0.1 mL, Intradermal (ID)<br>|
| Experimental: Influenza Virus Vaccine Formulation 2<br>Influenza Virus Vaccine Formulation 2 | Biological: Split, Inactivated, Trivalent Influenza Vaccine (Intradermal Formulation 2)<br>* 0.1 mL, Intradermal (ID)<br>|
| Active Comparator: Fluzone® Elderly Group<br> | Biological: Split, Inactivated, Trivalent Influenza Vaccine (Standard dose)<br>* 0.5 mL, Intramuscular (IM)<br>* Other names: Fluzone®;|
| Active Comparator: Fluzone® High-dose Group<br>Participants enrolled at age ≥ 65 years | Biological: Split, Inactivated, Trivalent Influenza Vaccine (High-dose)<br>* 0.5 mL, Intramuscular (IM)<br>* Other names: Fluzone® High-dose;|
| Active Comparator: Fluzone® Adults Group<br>Participants enrolled at age 18-49 years. | Biological: Split, Inactivated, Trivalent Influenza Vaccine (Standard dose)<br>* 0.5 mL, Intramuscular (IM)<br>* Other names: Fluzone®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) Before and After Vaccination With Fluzone Intradermal or Fluzone High Dose or Fluzone Intramuscular Vaccine. | Serum antibody titers for the Influenza vaccine serogroups A/H1N1, A/H3N2, and B were assessed by hemagglutinin inhibition (HAI) assay. | Day 0 and Day 28 post vaccination | 
| Percentage of Participants Who Achieved Seroconversion Post-Vaccination With Fluzone Intradermal or Fluzone High Dose or Fluzone Intramuscular Vaccine | Seroconversion defined as either a pre-vaccination hemagglutination inhibition (HAI) titer < 1:10 and a post vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and a minimum four fold increase at one month post-vaccination. | Day 28 post-vaccination | 
| Percentage of Participants Who Achieved Seroprotection Before and Post-vaccination With Fluzone Intradermal or Fluzone High Dose or Fluzone Intramuscular Vaccine. | Seroprotection was defined as a Hemagglutination inhibition (HAI) titer ≥ 1:40 | Day 0 and Day 28 post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Solicited Injection Site or Systemic Reactions Post-vaccination With Either Fluzone Intradermal or Fluzone High Dose or Fluzone Intramuscular Vaccine. | Solicited injection site reactions: Pain, Pruritus, Erythema, Swelling, Induration, and Ecchymosis. Solicited systemic reactions: Fever (Temperature), Headache, Malaise, Myalgia, and Chills | Days 0 through 7 post-vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Orthomyxoviruses, Myxovirus Infection, Inactivated Split-virion influenza vaccine, Elderly