Hepatitis B
Conditions
Keywords
hepatitis B, hepatitis B vaccine, immunogenicity, adults
Brief summary
The objective of this study is to evaluate the immunogenicity and Anti-HBV antibody persistence of hepatitis B vaccine with different doses and schedules. Hepatitis B vaccine with the regimens of 20μg, 0-1-6 mon and 60μg,0-1 or 0-2 mon will be administered to young adults, and the comparative immunogenicity among the three groups will be measured at 1 mon post-a series vaccination, 1- and 2-year after the first dose of the regimen. Furthermore, the safety of hepatitis B vaccine with different doses and schedules will also be evaluated.
Interventions
BIOLOGICALHepatitis B vaccine
Hepatitis B vaccine, 60 μg/1ml recombinant hepatitis B vaccine,20 μg/1ml recombinant hepatitis B vaccine, Shenzhen Kangtai Biological Products Co, LTD.
Sponsors
Guangxi Center for Disease Control and Prevention
Liuzhou City Center for disease control and prevention
Shenzhen Kangtai Biological Products Co., LTD
Peking University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
* Healthy subjects aged between 16 and 25 as established by medical history and clinical examination * Written informed consent will be obtained from each subject before the serum screening of HBV markers * Seronegative for HBsAg, anti-HBs antibody, anti-HBc antibody * Have never been immunized with HBV vaccine before
Exclusion criteria
* Subject has a medical history of allergic to any ingredient of vaccine * Family history of seizures or progressive neurological disease * Autoimmune disease or immunodeficiency * Women with pregnant * Bleeding disorder diagnosed by a doctor * Chronic diseases: hepatitis, tumor, tuberculosis,et.al * Any prior administration of immunoglobulins or blood products in the last 3 mon before recruitment * Subjects had a medical history of serious adverse reactions to vaccines
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity of Hepatitis B Vaccine With Different Doses and Schedules in Healthy Young Adults | one month after a series vaccination of the regimen | The measurements of anti-HBs antibodies were determined quantitatively by CMIA using the Architect i2000SR analyzer (Abbott, Chicago, IL, USA). The accepted protective serum anti-HBs level was ≥10 mIU/ml. Anti-HBs≥10 and \< 100 mIU/ml were considered low response, and anti-HBs concentrations ≥100 but \< 1000 mIU/ml were middle or moderate response, and hyper or high response was associated with an anti-HBs level ≥1000 mIU/ml. The GMCs of anti-HBs antibody will be compared among the three vaccine groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity of Hepatitis B Vaccine With Different Doses and Schedules in Healthy Young Adults | 1-year after the first dose of the regimens | The measurements of anti-HBs antibodies were determined quantitatively by CMIA using the Architect i2000SR analyzer (Abbott, Chicago, IL, USA). The accepted protective serum anti-HBs level was ≥10 mIU/ml. Anti-HBs≥10 and \< 100 mIU/ml were considered low response, and anti-HBs concentrations ≥100 but \< 1000 mIU/ml were middle or moderate response, and hyper or high response was associated with an anti-HBs level ≥1000 mIU/ml. The GMCs of anti-HBs will be compared among the three vaccine groups. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety of HBV Vaccine Determined by Number of Participants With Adverse Events | 0-3 day after the first dose of immunization | Participants were monitored for any adverse events occurring within 30 min after each injection for immediate reactions and instructed to measure axillary temperature and record selected injection-site reactions (pain, erythema, induration, swelling, pruritus, cutaneous rash) and systemic reactions (headache, vomiting, asthenia, allergic reaction, fatigue, diarrhea, myalgia, general malaise, etc.) on the day of vaccination and the subsequent 3 days. Adverse reactions were graded or categorized according to the standard guideline for adverse reactions grading in vaccine clinical trials as Grade 1-3. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 20μg, 0-1-6 117 young adults were administered with 20μg of hepatitis B vaccine according to the 0-1-6 mon schedule. | 117 |
| 60μg, 0-1 111 young adults were administered with 60μg of hepatitis B vaccine according to the 0-1 mon schedule. | 111 |
| 60μg, 0-2 125 young adults were administered with 60μg of hepatitis B vaccine according to the 0-2 mon schedule. | 125 |
| Total | 353 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 58 | 66 | 70 |
Baseline characteristics
| Characteristic | Total | 20μg, 0-1-6 | 60μg, 0-1 | 60μg, 0-2 |
|---|---|---|---|---|
| Age, Continuous | 20.20 years STANDARD_DEVIATION 1.05 | 20.32 years STANDARD_DEVIATION 1.13 | 20.11 years STANDARD_DEVIATION 0.94 | 20.18 years STANDARD_DEVIATION 1.07 |
| Region of Enrollment China | 353 participants | 117 participants | 111 participants | 125 participants |
| Sex: Female, Male Female | 114 Participants | 40 Participants | 32 Participants | 42 Participants |
| Sex: Female, Male Male | 239 Participants | 77 Participants | 79 Participants | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 117 | 2 / 111 | 5 / 125 |
| serious Total, serious adverse events | 0 / 117 | 0 / 111 | 0 / 125 |
Outcome results
Primary
Immunogenicity of Hepatitis B Vaccine With Different Doses and Schedules in Healthy Young Adults
The measurements of anti-HBs antibodies were determined quantitatively by CMIA using the Architect i2000SR analyzer (Abbott, Chicago, IL, USA). The accepted protective serum anti-HBs level was ≥10 mIU/ml. Anti-HBs≥10 and \< 100 mIU/ml were considered low response, and anti-HBs concentrations ≥100 but \< 1000 mIU/ml were middle or moderate response, and hyper or high response was associated with an anti-HBs level ≥1000 mIU/ml. The GMCs of anti-HBs antibody will be compared among the three vaccine groups.
Time frame: one month after a series vaccination of the regimen
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 20μg, 0-1-6 | Immunogenicity of Hepatitis B Vaccine With Different Doses and Schedules in Healthy Young Adults | 1847.99 mIU/ml |
| 60μg, 0-1 | Immunogenicity of Hepatitis B Vaccine With Different Doses and Schedules in Healthy Young Adults | 839.27 mIU/ml |
| 60μg, 0-2 | Immunogenicity of Hepatitis B Vaccine With Different Doses and Schedules in Healthy Young Adults | 1244.8 mIU/ml |
p-value: <0.05ANOVA
Secondary
Immunogenicity of Hepatitis B Vaccine With Different Doses and Schedules in Healthy Young Adults
The measurements of anti-HBs antibodies were determined quantitatively by CMIA using the Architect i2000SR analyzer (Abbott, Chicago, IL, USA). The accepted protective serum anti-HBs level was ≥10 mIU/ml. Anti-HBs≥10 and \< 100 mIU/ml were considered low response, and anti-HBs concentrations ≥100 but \< 1000 mIU/ml were middle or moderate response, and hyper or high response was associated with an anti-HBs level ≥1000 mIU/ml. The GMCs of anti-HBs will be compared among the three vaccine groups.
Time frame: 1-year after the first dose of the regimens
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 20μg, 0-1-6 | Immunogenicity of Hepatitis B Vaccine With Different Doses and Schedules in Healthy Young Adults | 1456.63 mIU/ml |
| 60μg, 0-1 | Immunogenicity of Hepatitis B Vaccine With Different Doses and Schedules in Healthy Young Adults | 256.30 mIU/ml |
| 60μg, 0-2 | Immunogenicity of Hepatitis B Vaccine With Different Doses and Schedules in Healthy Young Adults | 235.15 mIU/ml |
Secondary
Immunogenicity of Hepatitis B Vaccine With Different Doses and Schedules in Healthy Young Adults
The measurements of anti-HBs antibodies were determined quantitatively by CMIA using the Architect i2000SR analyzer (Abbott, Chicago, IL, USA). The accepted protective serum anti-HBs level was ≥10 mIU/ml. Anti-HBs≥10 and \< 100 mIU/ml were considered low response, and anti-HBs concentrations ≥100 but \< 1000 mIU/ml were middle or moderate response, and hyper or high response was associated with an anti-HBs level ≥1000 mIU/ml. The GMCs of anti-HBs antibody will be compared among the three vaccine groups. The dynamic changes of seroprotection rates and GMCs of anti-HBs antibody will also be analyzed over the 2 years.
Time frame: 2-year after the first dose of the regimens
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 20μg, 0-1-6 | Immunogenicity of Hepatitis B Vaccine With Different Doses and Schedules in Healthy Young Adults | 427.46 mIU/ml |
| 60μg, 0-1 | Immunogenicity of Hepatitis B Vaccine With Different Doses and Schedules in Healthy Young Adults | 89.74 mIU/ml |
| 60μg, 0-2 | Immunogenicity of Hepatitis B Vaccine With Different Doses and Schedules in Healthy Young Adults | 89.80 mIU/ml |
Other Pre-specified
Safety of HBV Vaccine Determined by Number of Participants With Adverse Events
Participants were monitored for any adverse events occurring within 30 min after each injection for immediate reactions and instructed to measure axillary temperature and record selected injection-site reactions (pain, erythema, induration, swelling, pruritus, cutaneous rash) and systemic reactions (headache, vomiting, asthenia, allergic reaction, fatigue, diarrhea, myalgia, general malaise, etc.) on the day of vaccination and the subsequent 3 days. Adverse reactions were graded or categorized according to the standard guideline for adverse reactions grading in vaccine clinical trials as Grade 1-3.
Time frame: 0-3 day after the first dose of immunization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 20μg, 0-1-6 | Safety of HBV Vaccine Determined by Number of Participants With Adverse Events | 2 number of participants |
| 60μg, 0-1 | Safety of HBV Vaccine Determined by Number of Participants With Adverse Events | 2 number of participants |
| 60μg, 0-2 | Safety of HBV Vaccine Determined by Number of Participants With Adverse Events | 5 number of participants |