Clinical Trial of Recombinant Hepatitis E Vaccine

Conditions

Hepatitis E

Keywords

hepatitis E, vaccine, efficacy

Brief summary

The primary purpose of this study is to determine whether the preventive hepatitis E are effective in the prevention of hepatitis E occurring at least 30 days after the administration of the third dose of vaccine. The secondary purpose of this study is to to evaluate the safety and immunogenicity and immunopersistence of the study vaccine. The initial study is planed to be ended on month 19 and the results were analysed and used for registration purpose. The extended study will be continued to assess the long-term efficacy, immunogenicity and safety.

Detailed description

Participants were randomly allocated into two groups, one received Hepatitis E vaccine and the other received hepatitis B vaccine. The study was carried out with two stages. In the first stage (phase 3a), 2 645 subjects was enrolled and actively monitored for solicited adverse events for 1 month after each injection. Serum samples from all the subjects were collected on day 0, 7m, 13m, 19m and timely after then to evaluate the immunogenicity and immuno-persistency. In the second stage (phase 3b), another 109 959 subjects was enrolled and monitored for solicited adverse events for 1 month after each injection. Serum samples from 9764 subjects among the phase 3b participants were collected on day 0, 7m, 19m and timely after then to evaluate the immunogenicity and immuno-persistency. Serious adverse events during the trial were followed up. Suspected hepatitis cases were identified through an established active hepatitis surveillance system. The sentinels of the system comprised all the healthcare facilities in the field. Suspected hepatitis was defined as when patients presented with systemic symptoms such as fatigue and/or loss of appetite for more than 3 days with alanine aminotransferase (ALT) exceeding 2.5 fold upper limit of normal range (ULN). Paired sera were obtained from these patients at the time of presentation and 2-6 weeks later. Sera were tested for the HEV antibodies and HEV-RNA.

Zhuang C, Liu X, Huang X, Lu J, Zhu K, Liao M, Chen L, Jiang H, Zang X, Wang Y, Yang C, Liu D, Zheng Z, Zhang X, Huang S, Huang Y, Su Y, Wu T, Zhang J, Xia N.

2025-02-174 citations

10.1038/s41467-025-57021-3

Persistence of hepatitis E vaccine-induced antibody response across different dosage schedules and baseline serostatus.

Zhu K, Liao M, Chen L, Lu J, Huang X, Zhuang C, Su Y, Huang S, Wu T, Zhang J, Xia N.

2024-12-19

10.1038/s41541-024-01041-5

Long-term efficacy of a recombinant hepatitis E vaccine in adults: 10-year results from a randomised, double-blind, placebo-controlled, phase 3 trial.

Huang S, Zhang X, Su Y, Zhuang C, Tang Z, Huang X, Chen Q, Zhu K, Hu X, Ying D, Liu X, Jiang H, Zang X, Wang Z, Yang C, Liu D, Wang Y, Tang Q, Shen W, Cao H, Pan H, Ge S, Huang Y, Wu T, Zheng Z, Zhu F, Zhang J, Xia N.

2024-02-1943 citations

10.1016/s0140-6736(23)02234-1

Long-term Antibody Persistence After Hepatitis E Virus Infection and Vaccination in Dongtai, China

Brittany Kmush, Huan Yu, Shoujie Huang, Xuefeng Zhang, Ting Wu et al. (7 authors)

Open Forum Infectious Diseases2019-03-2819 citations

10.1093/ofid/ofz144

Modeling the long-term antibody response of a hepatitis E vaccine.

Chen S, Zhou Z, Wei FX, Huang SJ, Tan Z, Fang Y, Zhu FC, Wu T, Zhang J, Xia NS.

2015-06-2822 citations

10.1016/j.vaccine.2015.06.050

Long-Term Efficacy of a Hepatitis E Vaccine

Jun Zhang, Xuefeng Zhang, Shoujie Huang, Ting Wu, Yuemei Hu et al. (22 authors)

New England Journal of Medicine2015-03-04369 citations

10.1056/nejmoa1406011

Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial.

Zhu FC, Zhang J, Zhang XF, Zhou C, Wang ZZ, Huang SJ, Wang H, Yang CL, Jiang HM, Cai JP, Wang YJ, Ai X, Hu YM, Tang Q, Yao X, Yan Q, Xian YL, Wu T, Li YM, Miao J, Ng MH, Shih JW, Xia NS.

2010-08-20545 citations

10.1016/s0140-6736(10)61030-6

Interventions

BIOLOGICALhepatitis E vaccine

Intramuscularly given at 0, 1, 6m for three doses.

BIOLOGICALHepatitis B vaccine

Intramuscularly given at 0, 1, 6m for three doses.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

16 Years to 65 Years

Healthy volunteers

Yes

Inclusion criteria

* Healthy people aged from 16 years to 65 years old at the time of the first vaccination, normal intelligence and agree to sign the informed consent form. * Subjects will reside in the study region in the next 19 months. * Free of history of hepatitis B or hepatitis E. * Can comply with the request of study. * Axillary temperature is below 37 degree centigrade.

Exclusion criteria

For dose 1: * Having other vaccine or immunoglobulin within two weeks; * Having allergic history to vaccine and medicine * Eclampsia, epilepsy, encephalopathy and history of mental disease or family; * Thrombocytopenia or other disturbance of blood coagulation which would lead to muscle injection taboo; * Fixed or suspected deficiency of immunologic function, containing immunosuppressant treatment(radiation therapy, chemical treatment, steroid hormone, antimetabolites, cytotoxic drugs), genetic defect(e.g. fabism), HIV or other factors; * congenital malformation, eccyliosis or severe chronic disease(e.g. Down Syndrome, diabetes, sickle cell anemia or mental disease); * fixed or suspected other disease including fever, active infection, liver and kidney disease, angiocardiopathy, malignancy, acute and chronic disease; * joining other clinical study undergoing; * women pregnant or in lactation. For dose 2 or 3: * Severe allergy for dose 1 or 2; * Severe adverse reaction associated with last vaccination; * New occurrence of symptoms meet dose 1

Design outcomes

Primary

Measure	Time frame
Rate of confirmed hepatitis E cases	One year since one month post the third injection

Secondary

Measure	Time frame
Persistency of IgG anti-HEV	One year
IgG anti-HEV seroconversion rate	On one month post the third injection

Countries

China

Outcome results

None listed