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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.
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%.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase I cohort 1 low-dose group | Experimental | 20 subjects aged 18-49 were enrolled and randomly assigned to the low-dose experimental group, and received one dose of the low-dose experimental vaccine. |
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| Phase I cohort 1 low-dose placebo group | Placebo Comparator | 10 subjects aged 18-49 were enrolled and randomly assigned to the low-dose placebo group, and received one dose of the low-dose placebo. |
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| Phase I cohort 2 high-dose group | Experimental | 20 subjects aged 18-49 were enrolled and randomly assigned to the high-dose experimental group, and received one dose of the high-dose experimental vaccine. |
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| Phase I cohort 2 high-dose placebo group | Placebo Comparator | 10 subjects aged 18-49 were enrolled and randomly assigned to the high-dose placebo group, and received one dose of the high-dose placebo. |
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| Phase I cohort 3 low-dose group |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Influenza Vaccine (Split Virion), Inactivated, Quadrivalent, ZFA02 Adjuvant (low dose) | Biological | Inject 1 dose of low-dose vaccine |
|
| Measure | Description | Time Frame |
|---|---|---|
| AE occurren | Number and incidence of all adverse events | within 30 days after vaccination |
| AESI occurrences | Number and incidence of all adverse events of special interest | within 30 days after vaccination |
| SAE occurrences | Number and incidence of all serious adverse events | within 12 months after vaccination |
| Serum alanine aminotransferase level | All participants in Phase I were tested for alanine aminotransferase levels before and on the 4th day after vaccination | on the 4th day after vaccination |
| Serum aspartate transaminase level | All participants in Phase I were tested for aspartate transaminase levels before and on the 4th day after vaccination | on the 4th day after vaccination |
| Serum total bilirubin level | All participants in Phase I were tested for total bilirubin levels before and on the 4th day after vaccination | on the 4th day after vaccination |
| Serum white blood cell level | All participants in Phase I were tested for white blood cell levels before and on the 4th day after vaccination | on the 4th day after vaccination |
| Serum platelet level |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Fei Jin | Contact | 13722795742 | ycjf3000@126.com |
| Name | Affiliation | Role |
|---|---|---|
| Fei Jin | Hebei Province Centers for Disease Control and Prevention | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hebei Province Centers for Disease Control and Prevention | Recruiting | Shijiazhuang | Hebei | China |
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| Experimental |
20 subjects aged 50 and above were enrolled and randomly assigned to the low-dose experimental group, and received one dose of the low-dose experimental vaccine. |
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| Phase I cohort 3 low-dose placebo group | Placebo Comparator | 10 subjects aged 50 and above were enrolled and randomly assigned to the low-dose placebo group, and received one dose of the low-dose placebo. |
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| Phase I cohort 4 high-dose group | Experimental | 20 subjects aged 50 and above were enrolled and randomly assigned to the high-dose experimental group, and received one dose of the high-dose experimental vaccine. |
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| Phase I cohort 4 high-dose placebo group | Placebo Comparator | 10 subjects aged 50 and above were enrolled and randomly assigned to the high-dose placebo group, and received one dose of the high-dose placebo. |
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| Phase II low-dose group (18-49 years old) | Experimental | 100 subjects aged 18-49 were enrolled and randomly assigned to the low-dose experimental group, and received one dose of the low-dose experimental vaccine. |
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| Phase II high-dose group (18-49 years old) | Experimental | 100 subjects aged 18-49 were enrolled and randomly assigned to the high-dose experimental group, and received one dose of the high-dose experimental vaccine. |
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| Phase II positive control group (18-49 years old) | Active Comparator | 50 subjects aged 18-49 were enrolled and randomly assigned to the positive control group, and received one dose of the positive control vaccine. |
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| Phase II low-dose group (50 years old and above) | Experimental | 100 subjects aged 50 and above were enrolled and randomly assigned to the low-dose experimental group, and received one dose of the low-dose experimental vaccine. |
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| Phase II high-dose group (50 years old and above) | Experimental | 100 subjects aged 50 and above were enrolled and randomly assigned to the high-dose experimental group, and received one dose of the high-dose experimental vaccine. |
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| Phase II positive control group (50 years old and above) | Active Comparator | 50 subjects aged 50 and above were enrolled and randomly assigned to the positive control group, and received one dose of the positive control vaccine. |
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| Influenza Vaccine (Split Virion), Inactivated, Quadrivalent, ZFA02 Adjuvant placebo (low dose) | Biological | Inject 1 dose of low-dose placebo |
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| Influenza Vaccine (Split Virion), Inactivated, Quadrivalent, ZFA02 Adjuvant (high dose) | Biological | Inject 1 dose of high-dose vaccine |
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| Influenza Vaccine (Split Virion), Inactivated, Quadrivalent, ZFA02 Adjuvant placebo (high dose) | Biological | Inject 1 dose of high-dose placebo |
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| Influenza Vaccine (Split Virion), Inactivated, Quadrivalent | Biological | Inject 1 dose of positive control vaccine |
|
All participants in Phase I were tested for platelet levels before and on the 4th day after vaccination |
| on the 4th day after vaccination |
| Serum hemoglobin level | All participants in Phase I were tested for hemoglobin levels before and on the 4th day after vaccination | on the 4th day after vaccination |
| Urinary protein level in urine | All participants in Phase I were tested for urinary protein levels in urine before and on the 4th day after vaccination | on the 4th day after vaccination |
| Urinary red blood cell level in urine | All participants in Phase I were tested for urinary red blood cell levels in urine before and on the 4th day after vaccination | on the 4th day after vaccination |
| Serum antibody level | Detect the levels of hemagglutination inhibition (HI) antibodies against influenza viruses H1N1, H3N2, and type B (B/Victoria and B/Yamagata). | 30 days after vaccination |
| ID | Term |
|---|---|
| D007251 | Influenza, Human |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D009976 | Orthomyxoviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D007252 | Influenza Vaccines |
| ID | Term |
|---|---|
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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