A phase IV clinical trial of Influenza Vaccine (Split Virion), Inactivated (Anflu®) developed by Sinovac Biotech Co., Ltd will be conducted in 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. All participants will be randomized to test group and control group in a ratio of 2:1 and receive one dose of vaccine (0.5 mL) of Sinovac Influenza Vaccine (Split Virion) , Inactivated (Anflu®) or Sanofi VAXIGRIP®, respectively.
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 .
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Hunan Provincial Maternal and Child Health Care Hospital
Changsha, China
Chengdu Women's and Children's Central Hospital
Chengdu, China
The First Affiliated Hospital of Chongqing Medical University
Chongqing, China
Nanfang Hospital, Southern Medical University
Guangzhou, China
The seroconversion rates (SCRs) of hemagglutination inhibition (HI) antibodies at day 28 ,as measured by HAI assay for vaccine-matched influenza A and B
Influenza A included H1N1 and H3N2 and influenza B strains included Victoria-lineage. Seroconversion is defined as either a baseline HI titer \<1:10 and a post-vaccination titer ≥1:40 or a baseline HI titer ≥1:10 and a minimum 4-fold rise in post-vaccination HI antibody titer.
Time frame: 28 days after vaccination
Incidence of adverse reactions within 28 days after vaccination
Incidence of adverse reactions within 28 days after vaccination. Adverse reactions include solicited and unsolicited adverse reactions. Solicited local (injection site) symptoms: pain, swelling, erythema, induration, pruritus; Solicited systemic (non-injection site) symptoms: fever (axillary temperature), fatigue, myalgia, headache, hypersensitivity reaction.
Time frame: 28 days after vaccination
The seroprotection rates (SPRs) of HI antibodies at day 28 ,as measured by HAI assay for vaccine-matched influenza A and B
Influenza A included H1N1 and H3N2 and influenza B strains included Victoria-lineage. Seroprotection is defined as an HI titer ≥1: 40.
Time frame: 28 days after vaccination
The geometric mean titers (GMTs) of HI antibodies at day 28 ,as measured by HAI assay for vaccine-matched influenza A and B
Influenza A included H1N1 and H3N2 and influenza B strains included Victoria-lineage. Log-transformed post-vaccination HI antibody titer will be the dependent variable, with treatment group as fixed effect and log-transformed pre-vaccination HI antibody titer as covariate. Least-squares mean differences with two-sided 95% CIs will be estimated and back-transformed via exponentiation to derive adjusted GMT ratios (experimental vs control) and corresponding two-sided 95% CIs.
Time frame: 28 days after vaccination
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Enrollment
150
Nanjing Drum Tower Hospita
Nanjing, China
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, China
The geometric mean fold rises (GMFRs) of HI antibodies at day 28 ,as measured by HAI assay for vaccine-matched influenza A and B
Influenza A included H1N1 and H3N2 and influenza B strains included Victoria-lineage. Geometric mean of antibody fold-rise with two-sided 95% CI will be calculated , along with the geometric mean ratio and its corresponding two-sided 95% CI.
Time frame: 28 days after vaccination
The SCRs of HI antibodies at delivery, as measured by HAI assay for vaccine-matched influenza A and B
Influenza A included H1N1 and H3N2 and influenza B strains included Victoria-lineage. Seroconversion is defined as either a baseline HI titer \<1:10 and a post-vaccination titer ≥1:40 or a baseline HI titer ≥1:10 and a minimum 4-fold rise in post-vaccination HI antibody titer.
Time frame: At the date of delivery , estimated to be 6-18 weeks after randomization.
The SPRs of HI antibodies at delivery ,as measured by HAI assay for vaccine-matched influenza A and B
Influenza A included H1N1 and H3N2 and influenza B strains included Victoria-lineage. Seroprotection is defined as an HI titer ≥1: 40.
Time frame: At the date of delivery , estimated to be 6-18 weeks after randomization.
The GMTs of HI antibodies at delivery,as measured by HAI assay for vaccine-matched influenza A and B
Influenza A included H1N1 and H3N2 and influenza B strains included Victoria-lineage. Log-transformed post-vaccination HI antibody titer will be the dependent variable, with treatment group as fixed effect and log-transformed pre-vaccination HI antibody titer as covariate. Least-squares mean differences with two-sided 95% CIs will be estimated and back-transformed via exponentiation to derive adjusted GMT ratios (experimental vs control) and corresponding two-sided 95% CIs.
Time frame: At the date of delivery , estimated to be 6-18 weeks after randomization.
The GMFRs of HI antibodies at delivery,as measured by HAI assay for vaccine-matched influenza A and B
Influenza A included H1N1 and H3N2 and influenza B strains included Victoria-lineage. Geometric mean of antibody fold-rise with two-sided 95% CI will be calculated , along with the geometric mean ratio and its corresponding two-sided 95% CI.
Time frame: At the date of delivery , estimated to be 6-18 weeks after randomization.
The SPRs of HI antibodies in cord blood at delivery ,as measured by HAI assay for vaccine-matched influenza A and B
Influenza A included H1N1 and H3N2 and influenza B strains included Victoria-lineage. Seroprotection is defined as an HI titer ≥1: 40.
Time frame: At the date of delivery, estimated to be 6-18 weeks after randomization
The GMTs of HI antibodies in cord blood at delivery, as measured by HAI assay for vaccine-matched influenza A and B
Influenza A included H1N1 and H3N2 and influenza B strains included Victoria-lineage. Log-transformed post-vaccination HI antibody titer will be the dependent variable, with treatment group as fixed effect and log-transformed pre-vaccination HI antibody titer as covariate. Least-squares mean differences with two-sided 95% CIs will be estimated and back-transformed via exponentiation to derive adjusted GMT ratios (experimental vs control) and corresponding two-sided 95% CIs.
Time frame: At the date of delivery, estimated to be 6-18 weeks after randomization
Incidence of serious adverse events from vaccination through 3 months after delivery.
Serious adverse events within 3 months after delivery.
Time frame: From vaccination to 3 months after delivery.
Pregnancy outcomes
Pregnancy outcomes: term birth, preterm birth, elective termination of pregnancy, fetal death, and gestational complications, etc.
Time frame: At the date of delivery, estimated to be 6-18 weeks after randomization
Neonatal birth outcomes
Birth outcomes: normal status, low birth weight, congenital malformations, neonatal NICU admission, and neonatal death, etc.
Time frame: 3 months after delivery