Hepatitis B Vaccine
Conditions
Keywords
Hepatitis B, Vaccine, Immunogenicity, methadone maintenance treatment, Randomized Controlled Trial
Brief summary
This is a randomized, controlled trial. The study will evaluate the immunogenicity, immune persistence, and safety of 20 µg and 60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6 in methadone maintenance treatment patients.
Detailed description
Comparison of 2 vaccination strategy against Hepatitis B in patients with Methadone Maintenance Treatment Intervention: Arm 1 : 60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6; Arm 2 : 20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6.
Interventions
BIOLOGICAL60 µg dose hepatitis B vaccine
three-dose, 60 µg per dose
BIOLOGICAL20 µg dose hepatitis B vaccine
three-dose, 20 µg per dose
Sponsors
Centers for Disease Control and Prevention, China
Shanxi Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Aged between 18 and 70 years at the enrolment * Serologically negative for hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) at enrollment * Willing to adhere to the study protocol
Exclusion criteria
* Being pregnant * Intolerance or allergy to any component of the vaccine * Any vaccination during the month preceding enrollment * Ongoing opportunistic infection * Liver disease * Hematological disorder * Cancer * Unexplained fever the week before enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and Rate of Participants With Anti-HBs Seroconversion at Month 7 | Month 7 | The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ） . The accepted protective serum anti-HBs level was ≥10 mIU/ml. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Adverse Events After Vaccination | Within 7 days after the vaccination, at Month 0, 1, and 6 | Occurrence of adverse reactions within 7 days after vaccination with the hepatitis B vaccine |
| Number and Rate of Participants With Anti-HBs Seroconversion at Month 18 | Month 18 | The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ） . The accepted protective serum anti-HBs level was ≥10 mIU/ml |
| Anti-HBs Concentration at Month 30 | Month 30 | The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ） |
| Number and Rate of Participants With Anti-HBs Seroconversion at Month 30 | Month 30 | The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ） . The accepted protective serum anti-HBs level was ≥10 mIU/ml |
| Anti-HBs Concentration at Month 42 | Month 42 | The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ） |
| Number and Rate of Participants With Anti-HBs Seroconversion at Month 42 | Month 42 | The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ） . The accepted protective serum anti-HBs level was ≥10 mIU/ml |
| Anti-HBs Concentration at Month 7 | Month 7 | The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ） |
| Anti-HBs Concentration at Month 12 | Month 12 | The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ） |
| Number and Rate of Participants With Anti-HBs Seroconversion at Month 12 | Month 12 | The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ） . The accepted protective serum anti-HBs level was ≥10 mIU/ml |
| Anti-HBs Concentration at Month 18 | Month 18 | The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ） |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number and Rate of Participants With Anti-HBs High-level Response at Month 18 | Month 18 | The measurements of anti-HBs antibodies were determined quantitatively by CMIA. and anti-HBs concentrations ≥100 mIU/mL were high-level response. |
| Number and Rate of Participants With Anti-HBs High-level Response at Month 30 | Month 30 | The measurements of anti-HBs antibodies were determined quantitatively by CMIA. and anti-HBs concentrations ≥100 mIU/mL were high-level response. |
| Number and Rate of Participants With Anti-HBs High-level Response at Month 42 | Month 42 | The measurements of anti-HBs antibodies were determined quantitatively by CMIA. and anti-HBs concentrations ≥100 mIU/mL were high-level response. |
| Number and Rate of Participants With Anti-HBs High-level Response at Month 12 | Month 12 | The measurements of anti-HBs antibodies were determined quantitatively by CMIA. and anti-HBs concentrations ≥100 mIU/mL were high-level response. |
| Number and Rate of Participants With Anti-HBs High-level Response at Month 7 | Month 7 | The measurements of anti-HBs antibodies were determined quantitatively by CMIA. and anti-HBs concentrations ≥100 mIU/ml were high-level response. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IM 20μg Group Participants received 3 intramuscular injections of 20 μg recombinant hepatitis B vaccine at months 0, 1 and 6. | 98 |
| IM 60μg Group Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6. | 98 |
| Total | 196 |
Baseline characteristics
| Characteristic | Total | IM 20μg Group | IM 60μg Group |
|---|---|---|---|
| Age, Continuous | 43.2 years STANDARD_DEVIATION 7.5 | 42.5 years STANDARD_DEVIATION 7.5 | 44.0 years STANDARD_DEVIATION 7.5 |
| Race/Ethnicity, Customized Han ethnicity | 159 Participants | 76 Participants | 83 Participants |
| Race/Ethnicity, Customized minority ethnicity | 37 Participants | 22 Participants | 15 Participants |
| Region of Enrollment China Rural | 39 Participants | 22 Participants | 17 Participants |
| Region of Enrollment China Urban | 157 Participants | 76 Participants | 81 Participants |
| Sex: Female, Male Female | 41 Participants | 23 Participants | 18 Participants |
| Sex: Female, Male Male | 155 Participants | 75 Participants | 80 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 98 | 0 / 97 |
| other Total, other adverse events | 7 / 98 | 8 / 97 |
| serious Total, serious adverse events | 0 / 98 | 0 / 97 |
Outcome results
Primary
Number and Rate of Participants With Anti-HBs Seroconversion at Month 7
The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ） . The accepted protective serum anti-HBs level was ≥10 mIU/ml.
Time frame: Month 7
Population: 73 and 71 patients in the IM20 and IM60 groups completed the followed-up at months 7.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Number and Rate of Participants With Anti-HBs Seroconversion at Month 7 | 59 Participants |
| IM 60μg Group | Number and Rate of Participants With Anti-HBs Seroconversion at Month 7 | 62 Participants |
Secondary
Anti-HBs Concentration at Month 12
The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ）
Time frame: Month 12
Population: 60 and 61 patients in the IM20 and IM60 groups completed the followed-up at months 12.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IM 20μg Group | Anti-HBs Concentration at Month 12 | 125.9 mIU/mL |
| IM 60μg Group | Anti-HBs Concentration at Month 12 | 182.2 mIU/mL |
Secondary
Anti-HBs Concentration at Month 18
The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ）
Time frame: Month 18
Population: 47 and 43 patients in the IM20 and IM60 groups completed the followed-up at months 12.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IM 20μg Group | Anti-HBs Concentration at Month 18 | 382.2 mIU/mL |
| IM 60μg Group | Anti-HBs Concentration at Month 18 | 490.5 mIU/mL |
Secondary
Anti-HBs Concentration at Month 30
The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ）
Time frame: Month 30
Population: 46 and 42 patients in the IM20 and IM60 groups completed the followed-up at months 12.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IM 20μg Group | Anti-HBs Concentration at Month 30 | 239.9 mIU/mL |
| IM 60μg Group | Anti-HBs Concentration at Month 30 | 306.4 mIU/mL |
Secondary
Anti-HBs Concentration at Month 42
The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ）
Time frame: Month 42
Population: 45 and 40 patients in the IM20 and IM60 groups completed the followed-up at months 12.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IM 20μg Group | Anti-HBs Concentration at Month 42 | 88.6 mIU/mL |
| IM 60μg Group | Anti-HBs Concentration at Month 42 | 97.7 mIU/mL |
Secondary
Anti-HBs Concentration at Month 7
The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ）
Time frame: Month 7
Population: 73 and 71 patients in the IM20 and IM60 groups completed the followed-up at months 7 .
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IM 20μg Group | Anti-HBs Concentration at Month 7 | 630.4 mIU/mL |
| IM 60μg Group | Anti-HBs Concentration at Month 7 | 742.9 mIU/mL |
Secondary
Number and Rate of Participants With Anti-HBs Seroconversion at Month 12
The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ） . The accepted protective serum anti-HBs level was ≥10 mIU/ml
Time frame: Month 12
Population: 60 and 61 patients in the IM20 and IM60 groups completed the followed-up at months 12.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Number and Rate of Participants With Anti-HBs Seroconversion at Month 12 | 41 Participants |
| IM 60μg Group | Number and Rate of Participants With Anti-HBs Seroconversion at Month 12 | 43 Participants |
Secondary
Number and Rate of Participants With Anti-HBs Seroconversion at Month 18
The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ） . The accepted protective serum anti-HBs level was ≥10 mIU/ml
Time frame: Month 18
Population: 47 and 43 patients in the IM20 and IM60 groups completed the followed-up at months 12.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Number and Rate of Participants With Anti-HBs Seroconversion at Month 18 | 29 Participants |
| IM 60μg Group | Number and Rate of Participants With Anti-HBs Seroconversion at Month 18 | 29 Participants |
Secondary
Number and Rate of Participants With Anti-HBs Seroconversion at Month 30
The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ） . The accepted protective serum anti-HBs level was ≥10 mIU/ml
Time frame: Month 30
Population: 46 and 42 patients in the IM20 and IM60 groups completed the followed-up at months 12.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Number and Rate of Participants With Anti-HBs Seroconversion at Month 30 | 20 Participants |
| IM 60μg Group | Number and Rate of Participants With Anti-HBs Seroconversion at Month 30 | 25 Participants |
Secondary
Number and Rate of Participants With Anti-HBs Seroconversion at Month 42
The measurements of anti-HBs antibodies were determined quantitatively by CMIA（ Chemiluminescent Microparticle Immunoassay ） . The accepted protective serum anti-HBs level was ≥10 mIU/ml
Time frame: Month 42
Population: 45 and 40 patients in the IM20 and IM60 groups completed the followed-up at months 12.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Number and Rate of Participants With Anti-HBs Seroconversion at Month 42 | 14 Participants |
| IM 60μg Group | Number and Rate of Participants With Anti-HBs Seroconversion at Month 42 | 20 Participants |
Secondary
Occurrence of Adverse Events After Vaccination
Occurrence of adverse reactions within 28 days after vaccination with the hepatitis B vaccine
Time frame: Within 28 days after the vaccination, at Month 0, 1, and 6
Population: 196 patients were enrolled and randomized,195 patients received the first dose, 1 patients declined in IM60 group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Occurrence of Adverse Events After Vaccination | 2 Participants |
| IM 60μg Group | Occurrence of Adverse Events After Vaccination | 3 Participants |
Secondary
Occurrence of Adverse Events After Vaccination
Occurrence of adverse reactions within 7 days after vaccination with the hepatitis B vaccine
Time frame: Within 7 days after the vaccination, at Month 0, 1, and 6
Population: 196 patients were enrolled and randomized,195 patients received the first dose, 1 patients declined in IM60 group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Occurrence of Adverse Events After Vaccination | 7 Participants |
| IM 60μg Group | Occurrence of Adverse Events After Vaccination | 8 Participants |
Other Pre-specified
Number and Rate of Participants With Anti-HBs High-level Response at Month 12
The measurements of anti-HBs antibodies were determined quantitatively by CMIA. and anti-HBs concentrations ≥100 mIU/mL were high-level response.
Time frame: Month 12
Population: 60 and 61 patients in the IM20 and IM60 groups completed the followed-up at months 12.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Number and Rate of Participants With Anti-HBs High-level Response at Month 12 | 13 Participants |
| IM 60μg Group | Number and Rate of Participants With Anti-HBs High-level Response at Month 12 | 20 Participants |
Other Pre-specified
Number and Rate of Participants With Anti-HBs High-level Response at Month 18
The measurements of anti-HBs antibodies were determined quantitatively by CMIA. and anti-HBs concentrations ≥100 mIU/mL were high-level response.
Time frame: Month 18
Population: 47 and 43 patients in the IM20 and IM60 groups completed the followed-up at months 12.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Number and Rate of Participants With Anti-HBs High-level Response at Month 18 | 9 Participants |
| IM 60μg Group | Number and Rate of Participants With Anti-HBs High-level Response at Month 18 | 14 Participants |
Other Pre-specified
Number and Rate of Participants With Anti-HBs High-level Response at Month 30
The measurements of anti-HBs antibodies were determined quantitatively by CMIA. and anti-HBs concentrations ≥100 mIU/mL were high-level response.
Time frame: Month 30
Population: 46 and 42 patients in the IM20 and IM60 groups completed the followed-up at months 12.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Number and Rate of Participants With Anti-HBs High-level Response at Month 30 | 6 Participants |
| IM 60μg Group | Number and Rate of Participants With Anti-HBs High-level Response at Month 30 | 11 Participants |
Other Pre-specified
Number and Rate of Participants With Anti-HBs High-level Response at Month 42
The measurements of anti-HBs antibodies were determined quantitatively by CMIA. and anti-HBs concentrations ≥100 mIU/mL were high-level response.
Time frame: Month 42
Population: 45 and 40 patients in the IM20 and IM60 groups completed the followed-up at months 12.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Number and Rate of Participants With Anti-HBs High-level Response at Month 42 | 4 Participants |
| IM 60μg Group | Number and Rate of Participants With Anti-HBs High-level Response at Month 42 | 8 Participants |
Other Pre-specified
Number and Rate of Participants With Anti-HBs High-level Response at Month 7
The measurements of anti-HBs antibodies were determined quantitatively by CMIA. and anti-HBs concentrations ≥100 mIU/ml were high-level response.
Time frame: Month 7
Population: 73 and 71 patients in the IM20 and IM60 groups completed the followed-up at months 7.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Number and Rate of Participants With Anti-HBs High-level Response at Month 7 | 31 Participants |
| IM 60μg Group | Number and Rate of Participants With Anti-HBs High-level Response at Month 7 | 40 Participants |