A Clinical Trial to Evaluate the Safety and Immunogenicity of Norovirus Bivalent Vaccine

Study Overview
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Brief Summary
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A total of 450 subjects were enrolled, divided into four age groups, including 18-59 years, 6-17 years, 3-5 years, and 6-35 months. There are three types of the test vaccine component in each age group. A total of 30 people in each dose group were vaccinated with the test vaccine or placebo 1 or placebo 2, respectively, in a ratio of 3: 1: 1. The 18-59-year-old, 6-17-year-old, and 3-5-year-old age groups were vaccinated 2 times at a time interval of 28 days. The 6-35 month age group is divided into two groups, Group 1 is inoculated with 2 doses interval of 28 days each, and Group 2 is inoculated with 3 doses interval of 28 days.

Detailed Description
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From January to April 2020, this study was affected by the COVID-19 epidemic, which caused the two groups（6-17-year-old，3-5-year-old） of subjects to vaccinate beyond the window and deviate from the experimental plan. After communication between the researcher, the sponsor and the statistician, it was decided to restart the Phase I clinical trials of these two groups.

Official Title
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A Randomized, Blind, Placebo-controlled Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of Recombinant Norovirus Bivalent (GI. 1 / GII. 4) Vaccine (Hansenulapolymorpha) in Healthy People Aged 6 Months to 59 Years

Conditions
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Norwalk Gastroenteritis, Norovirus Infections

Intervention / Treatment
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* Biological: Norovirus Bivalent (GI.1 / GII.4) Vaccine（low）
* Biological: Norovirus Bivalent (GI.1 / GII.4) Vaccine（middle）
* Biological: Norovirus Bivalent (GI.1 / GII.4) Vaccine（high）
* Biological: Normal saline
* Biological: Aluminum adjuvant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 6 months to 59 years old, can provide legal identification of Chinese population; Based on medical history and physical examination, determined by the researcher as healthy; Volunteer legal guardians or trustees have the ability to understand (non-illiterate) research procedures, sign informed consent voluntarily with informed consent, and be able to comply with the requirements of clinical research protocols; Female subjects of childbearing age were not pregnant at the time of enrollment (negative urine pregnancy test), were not breastfeeding, and had no birth plan within the first 3 months after enrollment; effective contraceptive measures were taken within 2 weeks before enrollment. Exclusion Criteria: Axillary body temperature before inoculation on the day of entry> 37.0 ℃; Congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc .; Have a history of epilepsy, convulsions or convulsions, or a family history of mental illness; Those who received immunoenhancement or inhibitor therapy within months (continuous oral or instillation for more than 14 days); Have been diagnosed with congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia or other autoimmune diseases; No spleen or spleen function defect caused by any situation; Severe liver and kidney disease, drug-uncontrollable hypertension (systolic blood pressure> 140mmHg, diastolic blood pressure> 90mmHg), diabetic complications, malignant tumors, various acute diseases or chronic attacks of acute diseases; Have a history of chronic gastrointestinal diseases, diarrhea or other digestive system diseases, and have had gastroenteritis requiring treatment in the past 7 days;. Have a history of abnormal coagulation function (such as coagulation factor deficiency, coagulopathy); Have a history of severe allergic reactions to vaccination; are allergic to any component of the test vaccine; Live attenuated vaccine within14 days; other vaccines received within 7 days; Participating in other clinical trials in the near future; The investigator judges other circumstances that are not suitable for participation in this clinical trial. In addition to the general exclusion criteria, specific populations should also adhere to the following exclusion criteria: Premature birth (delivery before the 37th week of pregnancy), low weight (birth <2300g) infants under 24 months of age; History of salvage, birth apnea, or other causes of salvage, neurological damage, severe chronic disease (such as Down syndrome, sickle cell anemia, or neurological disorders) in children under 24 months of age.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vaccine group 1<br>vaccine produced by NVSI , Specification: GI.1 / GII.4 (low), 0.5ml / dose | Biological: Norovirus Bivalent (GI.1 / GII.4) Vaccine（low）<br>* Norovirus Bivalent (GI.1 / GII.4) Vaccine（low）administered intramuscularly according to a 0, 28，（56） day vaccination schedule<br>|
| Experimental: vaccine group 2<br>vaccine produced by NVSI , Specification: GI.1 / GII.4 (middle), 0.5ml / dose | Biological: Norovirus Bivalent (GI.1 / GII.4) Vaccine（middle）<br>* Norovirus Bivalent (GI.1 / GII.4) Vaccine（middle）administered intramuscularly according to a 0, 28，（56） day vaccination schedule<br>|
| Experimental: vaccine group 3<br>vaccine produced by NVSI , Specification: GI.1 / GII.4 (high), 0.5ml / dose | Biological: Norovirus Bivalent (GI.1 / GII.4) Vaccine（high）<br>* Norovirus Bivalent (GI.1 / GII.4) Vaccine（high）administered intramuscularly according to a 0, 28，（56）day vaccination schedule<br>|
| Placebo Comparator: Normal saline<br>（0.5ml / dose）produced by NVSI | Biological: Normal saline<br>* Normal saline administered intramuscularly according to a 0, 28 ，（56）day vaccination schedule<br>|
| Placebo Comparator: Aluminum adjuvant<br>（0.5ml / dose）produced by NVSI | Biological: Aluminum adjuvant<br>* Aluminum adjuvant administered intramuscularly according to a 0, 28，（56） day vaccination schedule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AE of local and systemic reactions within 30 minutes after each dose |  | 30 minutes | 
| All active AEs within 0-7 days after each dose | Active AE: Local and systemic adverse reactions occurring within 0-7 days after each dose of vaccination | 7 days | 
| All non-active collection AEs within 0-28（30） days after each dose | Adverse events other than active AE include solicitation adverse events reported in addition to the specified solicitation time window | 28（30） days | 
| All SAEs within 6 months after the last dose is vaccinated |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calculate geometric mean titer (GMT) of NoV GI.1 and GII.4 IgG antibodies |  | 28 days after the full vaccination | 
| Calculate positive rate of NoV GI.1 and GII.4 IgG antibodies |  | 28 days after the full vaccination | 
| Calculate NoV GI.1 and GII.4 HBGA-blocking antibody titers |  | 28 days after the full vaccination | 
| Calculate NoV GI.1 and GII.4 HBGA-blocking antibody positive rates |  | 28 days after the full vaccination |