Phase Ⅲ, Clinical Trial to Compare an Inactivated Quadrivalent Influenza Vaccine and a Licensed Vaccine in Chile

A Phase III, Randomized, Double-blind and Controlled Clinical Trial to Evaluate the Immunogenicity and Safety of Influenza Vaccine, Inactivated, Quadrivalent Developed by Sinovac Biotech Co., Ltd. Compared to a Licensed Quadrivalent Influenza Vaccine, VaxigripTetra™, in Individuals Aged 3 Years and Older in Chile

This study compares the immunogenity and safety of quadrivalent inactivated influenza vaccines. The experimental group receives the quadrivalent influenza vaccine developed by Sinovac Biotech Co., Ltd and the control group immunized with Vaxigrip Tetra™. The group has 1600 persons from general population 3 years and older. The design is double-blind and randomized. The primary outcome is the immunogenicity against the 4 strains of influenza included in both vaccines.

The study is designed to evaluate the immunogenicity of the quadrivalent inactivated-virus influenza vaccine developed by Sinovac Biotech Co., Ltd against Vaxigrip Tetra™. The population included in the study is healthy subjects 3 years and older, being 800 individuals 10 years old or less and 800 over 18 years, randomized 1:1 to experimental vaccine or Vaxigrip Tetra™. Volunteers 8 years old or less, without history of previous influenza infection will receive 2 doses of vaccine, al other individuals will receipt 1 dose of vaccine. Immunogenicity will be assessed one month after the last dose of vaccine, humoral responses will be determined for all patients meanwhile ome subgroup of patients will have a determination of cellular immunity also. Subjects will be follow up for one month, adverse events will be assessed during this time.

Inclusion Criteria:

1. Volunteers age 3 years and older, in good health or medically stable;

2. Written informed consent obtained from subjects or/and legal guardian;

3. No receipt of influenza vaccines within 6 months or plans to receive any influenza vaccines during the study;

4. Female subjects of non-childbearing may be enrolled in the study. Nonchildbearing potential is defined as surgically sterile (history of bilateral tubal ligation, bilateral oophorectomy, hysterectomy) or premenarche or postmenopausal (defined as amenorrhea for ≥ 12 consecutive months prior to screening without an alternative medical cause).

5. Female subjects of childbearing potential may be enrolled in the study, if the subject:

   • Has a negative pregnancy test on the day of the first dose (day 0);
   • Has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first dose and until at least 28 days after vaccination.

Exclusion Criteria:

1. History of seasonal influenza within 6 months prior to the study entry;

2. Axillary temperature ≥37.3℃;

3. History of Guillain-Barré syndrome within 6 weeks of receipt of prior influenza vaccine.

4. History of allergy to any vaccine, or any ingredient of the experimental vaccine.

5. Serious adverse reaction(s) to the vaccine, such as urticaria, dyspnea or angioneurotic edema, etc.;

6. History of serious neurological disorder (such as epilepsy, convulsions, etc.) , or mental illness;

7. Autoimmune disease or immunodeficiency/immunosuppressive, or any immunosuppressant receipt within 6 months prior to the study entry;

8. Significant chronic illnesses that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion (may include, but are not limited to cardiovascular disease, hypertension and diabetes that cannot be controlled by drugs, liver or kidney disorders, HIV infection or malignant tumor;

9. Acute central nervous system diseases such as encephalitis/myelitis, acute disseminating encephalomyelitis, and related disorders;

10. Absence of spleen, functional absence of spleen, and absence or removal of spleen under any circumstances;

11. Diagnosed coagulation function abnormal (e.g., coagulation factor deficiency, coagulation disorder, or platelet abnormalities), or obvious bruising or coagulation disorders;

12. Alcoholism or history of drug abuse

13. Acute disease or acute stage of chronic disease within 7 days prior to study entry;

14. Received blood products within 3 months prior to study entry;

15. Received any live attenuated vaccine within 14 days prior to study entry or any subunit vaccine or inactivated vaccine within 7 days prior to study entry;

16. Pregnant women or lactating women;

17. Subjects participate other clinical trials (licensed or unlicensed vaccines, drugs, organisms, devices, blood products or drugs) during the study period;

18. Any other factors which are unsuitable for participation in the clinical trial as judged by the investigator.

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