Seasonal Trivalent Inactivated Split Virion Influenza Vaccine Clinical Trial (IVACFLU-S) - PHASE 2/3

A Phase 2/3 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

This Phase 2/3 study assessed whether a single dose of seasonal trivalent inactivated split virion influenza vaccine (IVACFLU-S) is safe and well-tolerated in adults 18 to 60 years of age; and whether it will induce immune responses to each of the 3 vaccine antigens to meet 1 or both age group-specific Vietnam Ministry of Health (MOH) licensure requirements.

Seasonal influenza viruses circulate widely and cause disease in humans every year. Seasonal influenza viruses evolve continuously, which means that people can get infected multiple times throughout their lives. Therefore the components of seasonal influenza vaccines are reviewed frequently (currently biannually) and updated periodically to ensure continued effectiveness of the vaccines. The World Health Organization (WHO) recommended that influenza vaccines for use in the 2016-2017 northern hemisphere influenza season contain the following viruses:

• NYMC BX-35 reassortant of B/Brisbane/60/2008 (B)
• NYMC X-179A reassortant of A/California/7/2009 (H1N1)
• NYMC X-263B reassortant of H3/A/Hong Kong/4801/2014 (H3N2)

Among circulating influenza B viruses, there were 2 distinct lineages. The B/Brisbane/60/2008-like viruses were from the influenza B/Victoria lineage and represented the predominant circulating influenza B virus. The preclinical evaluation was conducted with all 3 lots of seasonal vaccine used in the Phase 1 study.The Phase 1 study of the IVACFLU-S that was completed in March 2016 identified no safety concerns and demonstrated the vaccine to be highly immunogenic. Given the promising findings, the current study proposed to expand on the safety data of the vaccine, to confirm the immunological findings, and by including individuals up to age 60 to seek regulatory approval for indication in nonelderly adults based on the Vietnam MOH Guidance on Clinical Trial of Influenza Vaccine serological criteria for assessing seasonal influenza.

Phase 2 was conducted at 1 site (District Health Center of Ben Luc, Long An, Vietnam). Subjects were from two age groups: 18-45 years and 46-60 years. Vaccine safety was determined by the Protocol Safety Review Team (PSRT) and approved by Vietnam Ministry of Health (MOH) before starting Phase 3.

Phase 3 was conducted at 2 sites: District Health Center (DHC) of Ben Luc, Long An, Vietnam; and DHC of Long Thanh, Dong Nai. Subjects were from two age groups: 18-45 years and 46-60 years. Both safety and immunogenicity were assessed.

Inclusion criteria:

• Aged 18 through 60 years on the day of screening/enrollment.
• Literate (by self-report) and willing to provide written informed consent.
• Able to attend all scheduled visits and to comply with all study procedures.
• Healthy or medically stable, as established by medical history and physical examination. For individuals with medical conditions, symptoms/signs, if present must be stable under controlled or unchanged for the past 3 months. If medication is used to treat the condition, the medication dose must have been stable for at least 1 month preceding vaccination.

For female subjects:

• Not breastfeeding or pregnant (based on negative urine pregnancy test) or plan to become pregnant up to Day 22. Women who are not surgically sterile (hysterectomy or tubal ligation) or post-menopausal for more than 1 year must have negative pregnancy test and, be willing to utilize reliable birth control measures (intrauterine device, hormonal contraception, condom or diaphragm with spermicide) through the Day 22 visit.

Exclusion criteria:

• Current or recent (within 2 weeks of enrollment) acute severe illness with or without fever.
• Participation in another clinical study involving any therapy within the previous 3 months or planned enrollment in such a study 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.
• Received seasonal influenza vaccine in last 6 months
• 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.
• Known or suspected congenital or acquired immunodeficiency.
• Chronic administration (defined as more than 14 consecutively-prescribed days) of immunosuppressants or other immune-modulating therapy within 6 months prior to study enrollment. (For corticosteroids, this means prednisone or equivalent, ≥ 0.5 mg/kg/day; topical steroids are allowed).
• Unstable illness by history or physical examination that in the opinion of the Investigator, might interfere with the conduct or results of the study or pose additional risk to the subject.
• Hypersensitivity after previous administration of any vaccine.
• Suspected or known hypersensitivity to any of the study vaccine components, including chicken or egg protein, and rubber (from the vaccine vial stoppers).
• Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion.
• Known active tuberculosis or symptoms of active tuberculosis, regardless of cause (self-report).
• Current alcohol or drug addiction that in the opinion of the Investigator, might interfere with the ability to comply with study procedures.
• History of Guillain-Barré Syndrome
• Neoplastic disease or any hematologic malignancy.
• 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.