Safety, Immunogenicity, and Immune Persistence Study of an Inactivated Hepatitis A Vaccine

Study Overview
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Brief Summary
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A double-blind, randomized and controlled clinical trial was conducted in healthy children aged from 1 to 8 years to evaluate the immunogenicity and safety of three consecutive lots of a preservative-free inactivated hepatitis A vaccine (Healive®). Participants who completed their primary vaccination were invited to participate in the follow-up phase. Written informed consents were obtained from them. The follow-up study was open-label. These subjects were visited in the next 11 years for blood sampling and assessment of immune persistence induced by vaccination.

Detailed Description
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The investigated vaccine is an inactivated, adjuvanted and preservative-free hepatitis A vaccine. Each dose contained 250 U HAV antigen in 0.5 milliliter. Total 400 subjects were enrolled and assigned into four groups, each receiving one of the three lots of Healive® or an established control vaccine at month 0 and 6. Anti-HAV titers were determined at month 1, 6 and 7. Anti-HAV titer over 20 mIU/ml is defined as seroprotection. After the full immunization schedule, written informed consents were obtained from subjects who would like to participate in the follow-up study. Blood samples of these subjects were collected at month 18, 30, 42, 54, 66, 112,138 after the first injection to evaluate the seroconversion rates (SCRs) and geometric mean concentrations (GMCs) of antibody against hepatitis A virus. Serological results of the follow-up study were then used to explore suitable statistical model for predicting the persistence of hepatitis A vaccine-induced antibodies.

Official Title
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The Phase Ⅳ Clinical Trial to Evaluate the Safety, Immunogenicity, and Immune Persistence of Three Consecutive Lots of an Inactivated Hepatitis A Vaccine in Healthy Children

Conditions
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Hepatitis A

Intervention / Treatment
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* Biological: Healive® Lot 1
* Biological: Healive® Lot 2
* Biological: Healive® Lot 3
* Biological: Havrix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Health children from 1 to 10 years Not participate in any other trial during the course of the trial Informed consent Exclusion Criteria: Any history of allergic reactions or convulsions following vaccination Other known or planned vaccination within 1 month prior to the study and during the study period Any chronic illness/disease including virus hepatitis, tuberculosis and epilepsy Presence of any congenital abnormality, upgrowth obstacle Any history/suspicion/presence of neurology and Lunacy Any current or foreseeable use of immunosuppressors (i.e. corticosteroids , immunoglobulins) within 1 month prior to the vaccination and during the period of the study Contraindication to intramuscularly injection due to thrombocytopenia or other bleeding disorders Abnormal ALT Positive markers for anti-HAV and HBV（HBsAg）infection Presence of fever at the time of vaccination, i.e. body temperature (by mouth) > 37.0 centigrade.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 10 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1: Healive® Lot 1<br> | Biological: Healive® Lot 1<br>* Inactivated hepatitis A vaccine manufactured by Sinovac Biotech Co., Ltd.; two-dose regimen with 6 months apart<br>|
| Experimental: 2: Healive® Lot 2<br> | Biological: Healive® Lot 2<br>* Inactivated hepatitis A vaccine manufactured by Sinovac Biotech Co., Ltd.; two-dose regimen with 6 months apart<br>|
| Experimental: 3: Healive® Lot 3<br> | Biological: Healive® Lot 3<br>* Inactivated hepatitis A vaccine manufactured by Sinovac Biotech Co., Ltd.; two-dose regimen with 6 months apart<br>|
| Active Comparator: 4: control vaccine (Havrix)<br> | Biological: Havrix<br>* Inactivated hepatitis A vaccine manufactured by GlaxoSmithKline Biologicals; two-dose regimen with 6 months apart<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-HAV titer | To evaluate the immune responses to the inactivated hepatitis A vaccine by detecting the anti-HAV titer using microparticle enzyme immunoassay (MEIA) assay. | 7 months after the first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Solicited adverse reactions (AE): local reactions and systematic reactions | Solicited AEs were recorded until 72 hours after each injection | 72 hours after each injection | 
| Unsolicited adverse reactions (AE) | Unsolicited AEs were recorded until month 7 | 7 months after the first dose | 
| Change of anti-HAV titer: geometry mean titer(GMT) and seroconversion rate | Blood samples were collected at day 0, month 1, 6, 7, 18, 30, 42, 54, 66,112, 138 after the first dose to assess the change of long-term immune response. Anti-HAV antibodies were assessed by microparticle enzyme immunoassay (MEIA) assay (cut off: 20 mIU/ml) | baseline (day 0), month 1, 6, 7, 18, 30, 42, 54, 66,112,138 after the first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inactivated hepatitis A vaccine, Healive, safety, immunogenicity, immune persistence