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

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

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.

Study Overview

• Status: Completed
• Conditions: Norwalk Gastroenteritis; Norovirus Infections
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 510
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Henan
    • Hebi, Henan, China
      • qixian Center for Disease Control and Prevention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 59 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: National Vaccine and Serum Institute, China
• Collaborators: Zhengzhou University; Lanzhou Institute of Biological Products Co., Ltd; Beijing Zhong Sheng Heng Yi Pharmaceutical Technology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2019
• Primary Completion (Actual): December 13, 2020
• Study Completion (Actual): December 13, 2020

Study Registration Dates

• First Submitted: November 27, 2019
• First Submitted That Met QC Criteria: December 4, 2019
• First Posted (Actual): December 6, 2019

Study Record Updates

• Last Update Posted (Actual): April 22, 2021
• Last Update Submitted That Met QC Criteria: April 20, 2021
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Gastrointestinal Diseases; Gastroenteritis; Caliciviridae Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: CXSL1700011-I

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No