Safety and Immunogenicity Following Recombinant Hepatitis B (Bio Farma) Vaccine in Adults & Children

Study Overview
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Brief Summary
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This trial is an experimental, randomized, double blind, prospective intervention study Approximately 100 subjects will be enrolled in this trial, divided into 2 arms, as follow: For adult (18-40 years old)

Detailed Description
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Each study age group/arm will be divided into two groups of treatment. One group will receive investigational product and one other group will receive active comparator. This Study is sequential age de-escalation. To be conducted in heathy adults (18-40 years old) and followed by children (10-17 years old) ). Before the study started, the subjects will be assessed for anti HBs Antibody. For subjects with anti-HBs not protective (< 10mIU/mL) before immunization, additional 2 doses will be required with 1 month interval.

Official Title
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Safety and Preliminary of Immunogenicity Following Recombinant Hepatitis B (Bio Farma) Vaccine in Adults & Children (Phase I)

Conditions
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Hepatitis B

Intervention / Treatment
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* Biological: Recombinant Hepatitis B (Bio Farma) Vaccine
* Biological: Recombinant Hepatitis B (Bio Farma) Vaccine®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult Healthy individu as determined by clinical judgment, including a medical history, physical exam, rontgen thorax and laboratory results, which confirms the absence of a current or past disease state considered significant by the investigator. Subjects have been informed properly regarding the study and signed the informed consent form Subjects will commit to comply with the instructions of the investigator and the schedule of the trial Children: Healthy individu as determined by clinical judgment, including a medical history, physical exam and rontgen thorax which confirms the absence of a current or past disease state considered significant by the investigator. Subjects/parents/guardian(s) have been informed properly regarding the study and signed the informed consent form and Subject/parents/guardian(s) will commit to comply with the instructions of the investigator and the schedule of the trial. Exclusion Criteria: Subject concomitantly enrolled or scheduled to be enrolled in another trial Any direct relatives relationship with the study team. Evolving mild, moderate or severe illness, especially infectious diseases or fever (axillary temperature ³ 37.5°C) within the 48 hours preceding enrollment. Known history of allergy to any component of the vaccines (based on anamnesis) Known history of immunodeficiency disorder (HIV infection, leukemia, lymphoma, or malignancy) History of uncontrolled coagulopathy or blood disorders contraindicating for phlebotomy. Subject who has received in the previous 4 weeks a treatment likely to alter the immune response (intravenous immunoglobulins, blood-derived products, or corticosteroid therapy and other immunosuppresant). Any abnormality or chronic disease which according to the investigator might interfere with the assessment of the trial objectives. Pregnancy or planning a pregnancy within the next 3 months & lactation. (for Adults) Subject already immunized with any vaccine within 4 weeks prior and expects to receive other vaccines within 4 weeks following immunization. HbsAg positive Subjects with known history of Hepatitis B infection. Subjects who have received Hepatitis B vaccination which proven by vaccination records. Subject planning to move from the study area before the end of study period.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 40 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: Sequential Assignment
Interventional Model Description: This Study is sequential age de-escalation. To be conducted in heathy adults (18-40 years old) and followed by children (10-17 years old) )
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Recombinant Hepatitis B (Bio Farma) Vaccine<br>Recombinant Hepatitis B vaccine is an inactivated HbsAg produced in yeast cells (Hansenula polymorpha) using recombinant DNA technology. It is a whitish liquid produced by culture genetically engineered yeast cell which carry the relevant gene of the HbsAg and purified and inactivated by several physicochemical steps such as ultracentrifugation, column chromatography and formaldehyde treatment. | Biological: Recombinant Hepatitis B (Bio Farma) Vaccine<br>* Recombinant Hepatitis B vaccine produced by Bio Farma<br>|
| Active Comparator: Control Product: Recombinant Hepatitis B (Bio Farma) Vaccine®<br>Registered Recombinant Hepatitis B vaccine is an inactivated HbsAg produced in yeast cells (Hansenula polymorpha) using recombinant DNA technology. It is a whitish liquid produced by culture genetically engineered yeast cell which carry the relevant gene of the HbsAg and purified and inactivated by several physicochemical steps such as ultracentrifugation, column chromatography and formaldehyde treatment. | Biological: Recombinant Hepatitis B (Bio Farma) Vaccine®<br>* Registered Recombinant Hepatitis B vaccine produced by Bio Farma<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with Immediate reaction | Number of subjects with at least one immediate reaction (local reaction or systemic event) within 30 minutes after one dose or three doses of Hepatits B vaccination | 3 months | 
| percentage of subjects with Immediate reaction | Percentage of subjects with at least one immediate reaction (local reaction or systemic event) within 30 minutes after one dose or three doses of Hepatits B vaccination | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with Adverse Events from 1 day to 28 days after vaccination | Number of subjects with at least one of these adverse events, solicited or not, within 24 h, 48h, 72h and 28 days after each dose vaccination | 3 months | 
| Percentage of subjects with Adverse Events from 1 day to 28 days after vaccination | Percentage of subjects with at least one of these adverse events, solicited or not, within 24 h, 48h, 72h and 28 days after each dose vaccination | 3 months | 
| Number of subjects with Serious Adverse Events from 1 day to 28 days after vaccination | Number of subjects with serious adverse event from inclusion until 28 day after each dose vaccination. | 3 Months | 
| Percentage of subjects with serious Adverse Events from 1 day to 28 days after vaccination | Percentage of subjects with serious adverse event from inclusion until 28 day after each dose vaccination. | 3 Months | 
| Number of Lab Deviation for adults subjects in 7 days of immunization | Number of deviation from routine biochemical (SGOT, SGPT, Ureum, Creatinine) and Hematological (Hb, Hct, Dif, Leucocyte count, Total Leucocyte, total Eryhrocyte, total Thrombocyte) laboratory evaluation that probably related to the vaccination (adults subject). | 7 Days After 1st Vaccination | 
| Safety Comparison between each intervention group | incidence of any adverse event, compared between two intervention arms | 3 months | 
| Protectivity of Hepatitis B vaccine (number of subject with protective anti HbsAg) | Number of subjects with anti-HbsAg more than 10mIU/ml, 28 days after 1 dose or three doses of vaccination. | 3 months | 
| Protectivity of Hepatitis B vaccine (4 times increasing antibody) | - Number and percentage of subjects with more than 4 folds increasing antibody | 3 months | 
| Protectivity of Hepatitis B vaccine (Geometic Mean Titers) | - Geometric Mean Titers (GMT) following immunization | 3 months | 
| Anti-HBs description between groups | Number of subjects with protective Anti-HBs value, compared between intervention groups after vaccination. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccine, hepatitis b, infection, virus