Overview
This clinical trial adopts a seamless design of phase I/II, conducted in two stages: phase I and phase II. Phase I is the age/dose ramp up stage, and phase II is the dose expansion stage.The purpose of this clinical trial is to evaluate the safety and tolerability of different doses of Influenza Vaccine (Split Virion), Inactivated, Quadrivalent, ZFA02 Adjuvant，explore the immunogenicity of the vaccine, and determine the appropriate dose for later clinical trials of this product.
Description
Overall design:
Adopting a randomized, blinded research design. This experiment adopts a seamless connection design of Phase I/II, conducted in two stages: Phase I and Phase II. Phase I is the age/dose escalation stage, and Phase II is the dose extension stage.
Age/dose escalation stage: A randomized, blinded, placebo-controlled study design was used. 120 subjects were enrolled in the study, in order of age from 18 to 49 years old to 50 years old and above, from low dose to high dose. They were divided into four cohorts, with 30 subjects in each cohort (including 20 who received high-dose or low-dose experimental vaccines and 10 who received placebo). The first 6 subjects in each cohort were assigned to be sentinel group, and the researchers reviewed the safety data of the sentinel group within 7 days after vaccination. After confirming safety (not meeting the criteria for suspending/terminating the trial), the remaining 24 subjects in the cohort were enrolled.
Dose expansion stage: A randomized, blinded, positive controlled study design was used. 500 subjects were enrolled, divided into two age groups: 18-49 years old and 50 years old and above. 250 subjects were enrolled in each age group and randomly divided into low-dose group, high-dose group, and positive control group according to a 2:2:1 ratio. The proportion of people aged 60 and above in the population aged 50 and above shall not be less than 80%, and the proportion of people aged 70 and above shall not be less than 30%.
Eligibility
Inclusion Criteria:
- When signing the informed consent form, be at least 18 years old and provide valid identification;
- The subject is able to understand the procedures and methods of this clinical trial, has given sufficient informed consent, voluntarily participated, and signed an informed consent form by the subject themselves;
- On the day of enrollment, axillary temperature was ≤ 37.0 ℃;
- Female and male participants of childbearing age: agree to take effective contraceptive measures within 6 months after vaccination.
Exclusion Criteria:
- The laboratory test indicators specified in the protocol are abnormal and clinically significant before vaccination (only for Phase I);
- Have contracted influenza within the past 6 months prior to enrollment (confirmed by any clinical or microbiological method);
- Previously or currently suffering from autoimmune or immunodeficiency diseases;
- Previous history of severe allergies to any vaccine/drug or any component of the experimental vaccine, such as anaphylactic shock, allergic laryngeal edema, allergic purpura, thrombocytopenic purpura, respiratory distress, angioneurotic edema, or individuals with an allergic constitution (such as allergies to two or more drugs, food, or pollen); History of severe allergy to eggs or egg protein;
- Have received any influenza vaccine within the 6 months prior to enrollment, or plan to receive influenza vaccine other than the vaccine used in this trial during the trial period (before completing the immunization and collecting blood samples);
- Within 30 days prior to enrollment, any investigational or unregistered products (drugs, vaccines, or devices) have been used, or are planned to be used during the trial period (except for the vaccine used in this trial) (before completing the immunization and collecting blood samples);
- The interval between receiving attenuated live vaccines before enrollment is less than 30 days, and the interval between receiving other non live vaccines is less than 14 days;
- Within the first 3 days of enrollment, have experienced acute illness or are in the acute phase of chronic illness;
- Used antipyretic, analgesic, or anti allergic drugs within 3 days prior to enrollment;
- Use immunoglobulin and/or any blood products within 3 months prior to enrollment, or plan to use them during the trial period (before completing immunization and collecting blood samples);
- Long term use of immunosuppressants or other immunomodulatory drugs (defined as continuous use for more than 14 days) within the first 3 months of enrollment, such as a glucocorticoid dose of ≥ 0.5 mg/kg/day (inhalation and local steroid hormones are not restricted);
- Absence of spleen, functional absence of spleen, and splenectomy caused by any condition;
- Any obvious coagulation dysfunction or history of anticoagulant therapy;
- History of epilepsy, encephalopathy, and malignant tumors;
- Suffering from serious cardiovascular system diseases, serious hypertension with unstable drugs (systolic pressure ≥ 160mmHg and/or diastolic pressure ≥ 100mmHg), diabetes with serious complications and other serious chronic diseases;
- Currently suffering from respiratory system diseases (including pneumonia, tuberculosis, severe asthma, chronic bronchitis, etc.), acute liver and kidney diseases (severe impairment of liver and kidney function), mental disorders (such as schizophrenia, depression, affective disorders, etc.), etc;
- Women of childbearing age who are breastfeeding, pregnant, or have a positive urine pregnancy test before enrollment;
- Plan to move out of the local area before the end of the study or plan to leave the local area for a long time during the study visit;
- According to the researchers' judgment, the subjects have any other factors that are not suitable for participating in the clinical trial.