A Phase Ⅳ Clinical Trial of the Recombinant Hepatitis E Vaccine (Escherichia Coli)(the Chronic Hepatitis B Patients )

Study Overview
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Brief Summary
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This phase IV clinical study was designed to evaluate the immunogenicity and safety of Hecolin® in the chronic Hepatitis B patients on the clinical stability.

Detailed Description
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This phase IV clinical study was designed to evaluate the immunogenicity and safety of the recombinant Hepatitis E vaccine(Hecolin®), manufactured by Xiamen Innovax Biotech CO., LTD., in the chronic Hepatitis B patients on the clinical stability and aged over 30 years of age at enrollment. The study volunteers will receive the 3 doses of Hecolin® administered intramuscularly according to a 0-1-6 month schedule.

Official Title
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An Open, Pared Trial of Recombinant Hepatitis E Vaccine (Escherichia Coli) Hecolin® in the Chronic Hepatitis B Patients on the Clinical Stability .( Aged 30 Years or Over)

Conditions
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Hepatitis E

Intervention / Treatment
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* Biological: Recombinant Hepatitis E Vaccine (Escherichia Coli)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria(all volunteers): Aged over 30 years old on the day of enrollment Axillary temperature is below than 37.0 ℃. No administration of HEV vaccine before the study Judged as healthy and eligible for vaccination by the investigators through a selfreported medical history and some physical examinations. Able to understand this study information and willing to comply with all study requirements. Willing to participate in this study and sign informed consent form. Negative serological markers for hepatitis E Inclusion Criteria(experiment group): ALT < 1.5×ULN No spleen swelling,no cirrhosis and no hepatocellular carcinoma Inclusion Criteria(control group): 1. HBsAg(-) Exclusion Criteria: With clinical evidence of malignant tumor History of severe cardio-cerebrovascular disease Administration of hepatotoxicity drugs before or during the study Pregnancy,breast-feeding or plan to be pregnant in 7 months later Participated in any other clinical trial during the study period. Use of any investigational product or non-registered product (drug or vaccine)within 30 days preceding the first dose of the study vaccine or plan to use during the study period. Received immunosuppressed, immunoregulation therapy or corticosteroid systemic therapy for more than 14 days in the 6 months before entry, except local treatment. Administration of any immunoglobulin or blood products within 3 months preceding the first dose of the study vaccine,or plan to use during the study period. Administration of any inactivated vaccines within 14 days preceding the first dose of the study or attenuated live vaccines within 21 days preceding the first dose of the study. Had a fever (axillary temperature over 38°C) within 3 days or acute illness requiring systemic antibiotics or antiviral treatment within 5 days before vaccination. Immunodeficiency (such as HIV carriers), primary disease of important organs, malignant tumor, or any immune disease (such as systemic lupus erythematosus, arthritis pauperum, splenectomy or functional asplenia or other disease which might affect immune response). History of allergic disease or history of serious adverse events occurring after vaccination, i.e., allergy,urticaria, dyspnea, angioneurotic edema or abdominal pain. Allergic history to any component of this vaccine. Asthma that needed emergency treatment, hospitalization, oral or intravenous corticosteroid to keep stable in the past two years. Combining another severe internal medicine disease(such as severe hypertension, cardiopathy,diabetes and hyperthyroidism) Anomal coagulation function or coagulopathy diagnosed by doctor Epilepsy(not including alcohol epilepsy within 3 years prior to abstinence and simple epilepsy that do without curing within 3 years prior to the study ) Anomal psychology or mind affecting the individual's ability to obey the study requie Other medical, psychological, social or occupational factors that, according to the investigators' judgment,might affect the individual's ability to obey the protocol or sign the informed consent.

Ages Eligible for Study
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Minimum Age: 30 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: the chronic Hepatitis B patients<br>Participants in this arm are aged over 30 years and would receive three doses of Recombinant Hepatitis E Vaccine (Escherichia Coli)(Hecolin®) at 0,1,6 month. | Biological: Recombinant Hepatitis E Vaccine (Escherichia Coli)<br>* Participants would receive 3 doses of Recombinant Hepatitis E Vaccine (Escherichia Coli) intramuscularly at 0, 1, 6 month.<br>* Other names: Hecolin®;|
| Active Comparator: the healthy volunteer<br>Participants in this arm are aged over 30 years and would receive three doses of Recombinant Hepatitis E Vaccine (Escherichia Coli)(Hecolin®) at 0,1,6 month. | Biological: Recombinant Hepatitis E Vaccine (Escherichia Coli)<br>* Participants would receive 3 doses of Recombinant Hepatitis E Vaccine (Escherichia Coli) intramuscularly at 0, 1, 6 month.<br>* Other names: Hecolin®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Whose Anti-HEV Antibody Seroconverted at One Month After The Third Dose | Measure the number of participants whose anti-HEV antibody seroconverted at month 7 to evaluate the immunogenicity of the Hepatitis E vaccine. | Month 7 | 
| Geometric Mean Concentrations of Anti-HEV Antibody at One Month After The Third Dose | Measure the level of anti-HEV antibody in serum samples at month 7 to evaluate the immunogenicity of the Hepatitis E vaccine. Wu/ml：World Health Organization (WHO) units per ml. The WHO standard was used to calibrate the antibody quantitative reference. | Month 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Changes in Liver Function Index Before and One Month After the First Dose | ALT, AST and TBIL were detected in both groups to determine the liver function of participants. The grade of ALT, AST and TBIL was determined according to the rules issued by CFDA. The fluctuations were classified into three categories: no change indicated no grade change; processed indicated a change from normal to abnormal or an increase in grade; and improved indicated a change from abnormal to normal or a decrease in grade or the change from abnormal to normal. | Day 0-Month 1 | 
| Number of Participants With Changes in Liver Function Index Before and One Month After the Third Dose | ALT, AST and TBIL were detected in both groups to determine the liver function of participants. The grade of ALT, AST and TBIL was determined according to the rules issued by CFDA. The fluctuations were classified into three categories: no change indicated no grade change; processed indicated a change from normal to abnormal or an increase in grade; and improved indicated a change from abnormal to normal or a decrease in grade or the change from abnormal to normal. | Month 6-Month 7 | 
| Number of Participants With Changes in Liver Function Index Before The First Dose and One Month After the Third Dose | ALT, AST and TBIL were detected in both groups to determine the liver function of participants. The grade of ALT, AST and TBIL was determined according to the rules issued by CFDA. The fluctuations were classified into three categories: no change indicated no grade change; processed indicated a change from normal to abnormal or an increase in grade; and improved indicated a change from abnormal to normal or a decrease in grade or the change from abnormal to normal. | Day0-Month 7 | 
| Number of Participants Who Experienced Any Adverse Reactions/Events | Any adverse reactions/events contains solicited and unsolicited adverse reactions/events during the whole period of observation. | Day 0-Month 7 | 
| Number of Participants Who Experienced Solicited Adverse Reactions/Events | Number of participants who experienced local, system adverse reactions/events within 7 days after each vaccination. | Day 0-Day 7 | 
| Number of Participants Who Experienced Solicited Local Adverse Reactions/Events | Number of participants who experienced solicited local adverse reactions/events within 7 days after each vaccination. | Day 0-Day 7 | 
| Number of Participants Who Experienced Solicited System Adverse Reactions/Events | Number of participants who experienced solicited system adverse reactions/events within 7 days after each vaccination. | Day 0-Day 7 | 
| Number of Participants Who Experienced Unsolicited Adverse Reactions/Events | Number of participants who experienced unsolicited adverse reactions/events during the whole period of observation. | Day 0-Month 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis E