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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
60
0.5 mL of phosphate buffered saline
Hung Ha District Health Center
Thái Bình, Thai Binh Province, Vietnam
Number of Participants With Immediate Adverse Events
Any adverse event occurring within the 30 minute post vaccination period.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: Within 21 days post-vaccination
Number and Percentage of Participants With Serious Adverse Events (SAEs)
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Time frame: Over the entire study period (Day 91)
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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Pre- (Day 1) and Post-vaccination (Day 22)