A Phase IV Clinical Trial of Influenza Vaccine (Split Virion), Inactivatedin (Anflu®) Pregnant Women (AnFLU-PREG)

A phase IV clinical trial of Influenza Vaccine (Split Virion), Inactivated (Anflu®) developed by Sinovac Biotech Co., Ltd will be conducted in Chinese pregnant women.

A total of 150 healthy pregnant women aged 18~45 years at 22 to 34 weeks (+6 days) of pregnancy will be enrolled.The trial is a randomized, double-blind, positive controlled study to evaluate the immunogenicity and safety of Influenza Vaccine (Split Virion) ,Inactivated (Anflu®) manufactured by Sinovac. The active control vaccine is VAXIGRIP® manufactured by Sanofi.

For immunogenicity assessment, blood samples will be collected from participants prior to vaccination, 28 days post-vaccination, and at the end of pregnancy (at delivery) to evaluate antibody levels in pregnant women following influenza vaccination. Additionally, the cord blood samples will be collected at delivery to assess transplacental antibody transfer to the fetus. Antibodies will be tested using the hemagglutination-inhibition (HI) assay.

For safety assessment, any immediate adverse events within 30 minutes after vaccine administration, solicited local and systemic adverse events within 7 days and unsolicited adverse events within 28 days will be collected. Serious adverse events will be collected from the time of informed consent signature until 3 months after delivery (or until 3 months after the event if pregnancy termination occurs). Pregnancy and neonatal outcomes will be collected by medical record review .

Inclusion criteria

• Healthy pregnant women aged 18 to 45 years (inclusive) with stable health status, at 22 to 34 weeks (+6 days) of gestation. Gestational age is determined based on early ultrasound examination, or based on the last menstrual period if early ultrasound is unavailable.
• Participants are able to understand and sign the informed consent form voluntarily;
• Participants are willing and able to adhere to visit schedules and maintain accessible contact throughout the study period;
• Participants should provide verifiable identification;
• Have a singleton pregnancy;
• Have normal non-invasive prenatal DNA test and systematic ultrasound results during the current pregnancy; normal amniocentesis results are required if the test has been performed.

Exclusion criteria

• Have a history of two or more preterm deliveries (delivery before 37 weeks of gestation), previous infants with low birth weight (birth weight <2500 g), or a history of neonatal asphyxia or neonatal neurological damage;
• Have a history of multiple unexplained spontaneous abortions;
• Have received any influenza vaccine or the influenza vaccine for the current influenza season within 6 months prior to enrollment, or plan to receive influenza vaccination during the study period.
• Have suffered from seasonal influenza within 6 months prior to enrollment.
• Have a history of Guillain-Barré syndrome within 6 weeks after previous influenza vaccination.
• Have allergic reactions or other severe adverse reactions to any influenza vaccine or its components.
• Have severe autoimmune diseases or immunodeficiency diseases (including but not limited to active systemic lupus erythematosus, rheumatoid arthritis, asplenia, functional asplenia, and HIV infection) and are judged unsuitable for vaccination by the investigator.
• Abnormal coagulation function (such as coagulation factor deficiency, coagulation disorders or platelet abnormalities).
• Have severe chronic diseases (including but not limited to cardiovascular diseases, partial liver diseases, renal diseases or malignant tumors) that may interfere with the study as judged by the investigator.
• Have a current or previous history of severe neurological diseases (epilepsy, convulsions) or psychiatric disorders, or have a family history of psychiatric disorders.
• Received corticosteroids (adult prednisone ≥20 mg/day or equivalent) or other immunosuppressants for ≥14 days, or cytotoxic therapy within 6 months prior to vaccination, or plan to receive such therapy during the study period.
• Received immunoglobulins or other blood products within 3 months prior to vaccination, or plan to receive such products during the study period.
• Received any vaccine within 28 days prior to study vaccination, or plan to receive any vaccine within 28 days after study vaccination.
• Have enrolled in other clinical trials of investigational drugs or vaccines during the follow-up period, or plan to receive investigational drugs or vaccines during the study period.
• Have acute diseases or acute exacerbation of chronic diseases within 7 days before vaccination.
• Have fever on the scheduled vaccination day with an axillary temperature ≥37.3 °C before vaccination.
• Have clinically significant abnormal laboratory findings as judged by the investigator, or meet any of the following laboratory criteria: a) White blood cell count >15.0×10^9/L; b) Neutrophil percentage >85%; c) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times the upper limit of normal (2×ULN); d) Total bilirubin >2 times the upper limit of normal (2×ULN).
• Any other factors which are unsuitable for participation in the clinical trial as judged by the investigator.