Seasonal Trivalent Inactivated Split Virion Influenza Vaccine Clinical Trial (IVACFLU-S)

Study Overview
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Brief Summary
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This is a phase I, double-blind, randomized, placebo-controlled trial with two groups of subjects to receive seasonal trivalent inactivated split virion influenza vaccine (A/H1N1; A/H3N2 and B strains) or placebo (phosphate buffered saline). A total of 60 healthy male and female adults 18 through 45 years of age will be randomized to receive vaccine (30) or placebo (30).

Detailed Description
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This is a phase 1, single center, double blinded, randomized, placebo-controlled study. Sixty (60) healthy male and female adults, 18 to 45 years of age, will be enrolled into the trial. Subjects will be randomized 1:1 to one of two treatment allocations: 30 to vaccine, 30 to placebo. The study will utilize a randomized block design to assure a balance of 1:1 vaccine and placebo when all subjects are enrolled. The study will be double blinded, meaning the study subjects, investigators, and the sponsor will be unaware of the treatment allocated to each subject until the clinical trial database is declared final and locked. The study should take about 5 months to complete, with each subject involved for 3 months from the day of injection. The justification for the 3 month follow up, rather than 6 month follow up is that this is an inactivated vaccine that follows very standard manufacturing practices with standard antigens. The safety of inactivated influenza vaccines is well-established. Adding length to the follow up results in delays in future testing of the vaccine for licensure.

Official Title
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A Phase 1 Double Blinded, Randomized, Placebo-Controlled Study In Healthy Adult Volunteers In Vietnam To Examine The Safety And Immunogenicity Of A Seasonal Trivalent Inactivated Split Virion Influenza Vaccine (IVACFLU-S) Produced By IVAC

Conditions
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Influenza, Human

Intervention / Treatment
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* Biological: Trivalent Seasonal Influenza Vaccine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female adult 18 through 45 years of age at the enrollment visit. Literate (by self-report) and willing to provide written informed consent. Healthy, as established by the medical history, physical examination, and screening laboratory evaluations. Capable and willing to complete Diary Cards and willing to return for all follow-up visits. For females, willing to utilize reliable birth control measures (e.g., intrauterine device, hormonal contraception, condoms) through the Day 22 visit. Exclusion Criteria: Participation in another clinical trial involving any therapy within the previous three months or planned enrollment in such a trial during the period of this study. Receipt of any non-study vaccine within 4 weeks prior to enrollment or refusal to postpone receipt of such vaccines until after the Day 22 visit. Current or recent (within 2 weeks of enrollment) acute illness with or without fever. Receipt of immune globulin or other blood products within 3 months prior to study enrollment or planned receipt of such products prior to the Day 22 visit. Chronic administration (defined as more than 14 consecutively-prescribed days) of immunosuppressants or other immune-modulating therapy within six months prior to study enrollment. (For corticosteroids, this means prednisone or equivalent, 0.5 mg per kg per day; topical steroids are allowed.) History of asthma. Hypersensitivity after previous administration of any vaccine. Suspected or known hypersensitivity to any of the study vaccine components, including chicken or egg protein, antibiotics, and rubber (from the vaccine vial stoppers). Acute or chronic clinically significant pulmonary, cardiovascular, hepatobiliary, metabolic, neurologic, psychiatric or renal functional abnormality, as determined by medical history, physical examination or clinical laboratory screening tests, which in the opinion of the investigator, might interfere with the study objectives. History of any blood or solid organ cancer. History of thrombocytopenic purpura or known bleeding disorder. History of seizures. Known or suspected immunosuppressed or immunodeficient condition of any kind. Confirmed hepatitis B virus (HBV) or hepatitis C virus (HCV) infection Known human immunodeficiency virus (HIV) infection (self-report). Known active tuberculosis or symptoms of active tuberculosis, regardless of cause (self-report). History of chronic alcohol abuse and/or illegal drug use. Pregnancy or lactation. (A negative pregnancy test will be required before administration of study product for all women of childbearing potential.) History of Guillain-Barré Syndrome Any condition that, in the opinion of the investigator, would increase the health risk to the subject if he/she participates in the study or would interfere with the evaluation of the study objectives. Note: Minor out-of-range laboratory values no greater than Grade 1 will not be considered to be exclusionary at screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Trivalent Seasonal Influenza Vaccine<br>0.5 mL of seasonal trivalent influenza vaccine with 15 mcg of HA of each of 3 strains: NYMC BX-51B reassortant of B/Massachusetts/2/2012 NYMC X-179A reassortant of A/California/7/2009 (H1N1) NYMC X-223A reassortant of H3/A/Texas/50/2012 (H3N2) | Biological: Trivalent Seasonal Influenza Vaccine<br> <br> * Other names: IVACFLU-S;|
| Placebo Comparator: Placebo<br>This is the placebo comparator: 0.5 mL of Phosphate Buffered Saline | Other: Placebo<br>* 0.5 mL of phosphate buffered saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Immediate Adverse Events | Any adverse event occurring within the 30 minute post vaccination period. | 30-minute post-vaccination period. | 
| Number and Percentage of Participants Reporting Solicited Local Reactogenicity | Number of subjects reporting solicited local reactions (redness, swelling, pain, hardness, and tenderness) at the injection site post-vaccination with study vaccine or placebo. | 7-day period (Days 1-7) post-vaccination. | 
| Number and Percentage of Participants Reporting Solicited Systemic Reactogenicity | Number of subjects reporting solicted systemic reactions (fever, fatigue/malaise, muscle aches, joint aches, chills, nausea, vomiting, and headache) post-vaccination with study vaccine or placebo | 7-day period (Days 1-7) post-vaccination | 
| Number and Percentage of Participants With Unsolicited Adverse Events | Unsolicited AEs were any AEs that occurred any time after the vaccine/placebo was administered (temporally related to investigational product), whether or not deemed related to the product, and are not solicited (specifically asked of the subject). Unsolicited AEs were to be observed by the study center personnel while the subject was at the study center for a study visit or reported by the subject at any time. Any sign or symptom that would normally be considered a solicited AE (for example, fever, nausea, injection site pain) starting after 7 days post-vaccination were to be recorded as an unsolicited AE. In this study, laboratory results were considered AEs when (1) the result was judged to be clinically significant by the Principal Investigator, regardless of grade; or (2) the result is Grade 2 or higher. Note: all unsolicited AEs were mild in intensity. Please see Adverse Events section of this report for detailed information of AEs. | Within 21 days post-vaccination | 
| Number and Percentage of Participants With Serious Adverse Events (SAEs) |  | Over the entire study period (Day 91) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and Percentage of Subjects With Seroconversion Against Each of the 3 Antigens | Seroconversion is defined as a serum HAI titer meeting the following criteria: pre-vaccination titer <1:10 and a post-vaccination titer ≥ 1:40 or pre-vaccination titer ≥ 1:10 and at least a four-fold increase in post-vaccination measured on Day 22. | Day 22 | 
| Number and Percentage of Seroprotected Subjects Against 3 Strains of Influenza Vaccine | A seroprotected subject was defined as a vaccinated subject who had a serum Hemagluttination Inhibition (HAI) titer >/= 1:40. The 3 influenza strains assessed were B, H1, and H3. | Day 1 and Day 22 post vaccination | 
| Geometric Mean Titers (GMTs) of Serum Hemaggluntination Inhibition (HAI) Antibodies for Each Antigen | Geometric mean titers (GMTs) of Serum Hemaggluntination Inhibition (HAI) antibodies pre- (Day 1) and post-vaccination (Day 22) for each of the 3 antigens. | Pre- (Day 1) and post-vaccination (Day 22) | 
| Geometric Mean Fold Rises (GMFRs) of Serum Hemaggluntination Inhibition (HAI) Antibodies | Geometric mean fold rises (GMFRs) of serum hemaggluntination inhibition (HAI) antibodies post-vaccination/pre-vaccination for each of the 3 antigens | Day 22/Day1 | 
| Geometric Mean Neutralization Titers of Neutralizing Antibodies (MNT) Pre- (Day 1) and Post-Vaccination (Day 22) for Each of the 3 Antigens |  | Pre- (Day 1) and Post-vaccination (Day 22) | 
| Geometric Fold Rises (GMFRs) of Neutralizing Antibodies (MNT) Post-vaccination/Pre-vaccination for Each of the 3 Antigens |  | Pre- (Day 1) and Post-vaccination (Day 22) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Seasonal Influenza, Trivalent Vaccine, Inactivated Vaccine