Hepatitis B Vaccine
Conditions
Keywords
Hepatitis B, Vaccine, Randomized Controlled Trial, Hemodialysis, Immunogenicity
Brief summary
Intramuscular injection of 40 μg hepatitis B vaccine in a standard three-dose schedule or a four-dose schedule is recommended for hemodialysis patients. However, seroconversion rates are inadequate and persistence of immunity remains a challenge. 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 hemodialysis patients.
Detailed description
Participants are randomized in a ratio of 1:1 into 20 µg recombinant hepatitis B vaccine group or 60µg recombinant hepatitis B vaccine group.The 20 µg group will receive three intramuscular injections of the 20 µg recombinant hepatitis B vaccine, while the 60 µg group will receive three intramuscular injections of the 60 µg dose at months 0, 1 and 6, respectively. HBsAg and anti-HBs will be tested during the study period. Adverse reactions will be recorded after vaccination.
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
Suping Wang
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
* Having end-stage renal disease (ESRD) on maintenance hemodialysis * Aged between 18 and 70 years at enrollment * 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 * Acute cytolysis in the last three months before enrollment * Any vaccination during the month preceding enrollment * Intolerance or allergy to any component of the vaccine * Ongoing opportunistic infection * Hepatitis C virus infection * Hematological disorder * Cancer * Unexplained fever the week before enrollment * Immunosuppressive or immunomodulating treatment in the last six months * Renal transplantation or upcoming renal transplantation * Liver disease * Other immunocompromised condition not related to ESRD * An expected survival of \< 6 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Anti-HBs Seroconversion Rate at Month 7 | Month 7 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anti-HBs Seroconversion Rate at Month 36 | Month 36 | — |
| Anti-HBs Seroconversion Rate at Month 30 | Month 30 | — |
| Anti-HBs Seroconversion Rate at Month 24 | Month 24 | — |
| Anti-HBs Concentration at Month 7 | Month 7 | Anti-HBs concentration at month 7 as measured by CMIA |
| Anti-HBs Concentration at Month 12 | Month 12 | Anti-HBs concentration at month 12 as measured by CMIA |
| Anti-HBs Seroconversion Rate at Month 12 | Month 12 | — |
| Occurrence of Adverse Events After Vaccination | Within 7 days after the vaccination | Occurrence of adverse reactions within 7 days after vaccination with the hepatitis B vaccine |
| Anti-HBs Seroconversion Rate at Month 18 | Month 18 | — |
| Anti-HBs Seroconversion Rate at Month 42 | Month 42 | — |
Other
| Measure | Time frame |
|---|---|
| High-level Response Rate at Month 18 | Month 18 |
| High-level Response Rate at Month 30 | Month 30 |
| High-level Response Rate at Month 36 | Month 36 |
| High-level Response Rate at Month 42 | Month 42 |
| High-level Response Rate at Month 24 | Month 24 |
| High-level Response Rate at Month 12 | Month 12 |
| High-level Response Rate at Month 7 | Month 7 |
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. | 176 |
| IM 60μg Group Participants received 3 intramuscular injections of 60 μg recombinant hepatitis B vaccine at months 0, 1 and 6. | 176 |
| Total | 352 |
Baseline characteristics
| Characteristic | IM 20μg Group | IM 60μg Group | Total |
|---|---|---|---|
| Age, Continuous | 43.5 years STANDARD_DEVIATION 12.2 | 45.5 years STANDARD_DEVIATION 12 | 44.5 years STANDARD_DEVIATION 12.1 |
| Race/Ethnicity, Customized Han ethnicity | 176 Participants | 175 Participants | 351 Participants |
| Race/Ethnicity, Customized Hui ethnicity | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment China Rural | 87 Participants | 75 Participants | 162 Participants |
| Region of Enrollment China Urban | 89 Participants | 101 Participants | 190 Participants |
| Sex: Female, Male Female | 76 Participants | 88 Participants | 164 Participants |
| Sex: Female, Male Male | 100 Participants | 88 Participants | 188 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 174 | 0 / 175 |
| other Total, other adverse events | 8 / 174 | 8 / 175 |
| serious Total, serious adverse events | 0 / 174 | 0 / 175 |
Outcome results
Primary
Anti-HBs Seroconversion Rate at Month 7
Time frame: Month 7
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Anti-HBs Seroconversion Rate at Month 7 | 118 Participants |
| IM 60μg Group | Anti-HBs Seroconversion Rate at Month 7 | 132 Participants |
Secondary
Anti-HBs Concentration at Month 12
Anti-HBs concentration at month 12 as measured by CMIA
Time frame: Month 12
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IM 20μg Group | Anti-HBs Concentration at Month 12 | 407.8 mIU/mL |
| IM 60μg Group | Anti-HBs Concentration at Month 12 | 476.2 mIU/mL |
Secondary
Anti-HBs Concentration at Month 7
Anti-HBs concentration at month 7 as measured by CMIA
Time frame: Month 7
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IM 20μg Group | Anti-HBs Concentration at Month 7 | 1488.5 mIU/mL |
| IM 60μg Group | Anti-HBs Concentration at Month 7 | 1916.6 mIU/mL |
Secondary
Anti-HBs Seroconversion Rate at Month 12
Time frame: Month 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Anti-HBs Seroconversion Rate at Month 12 | 109 Participants |
| IM 60μg Group | Anti-HBs Seroconversion Rate at Month 12 | 114 Participants |
Secondary
Anti-HBs Seroconversion Rate at Month 18
Time frame: Month 18
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Anti-HBs Seroconversion Rate at Month 18 | 77 Participants |
| IM 60μg Group | Anti-HBs Seroconversion Rate at Month 18 | 96 Participants |
Secondary
Anti-HBs Seroconversion Rate at Month 24
Time frame: Month 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Anti-HBs Seroconversion Rate at Month 24 | 54 Participants |
| IM 60μg Group | Anti-HBs Seroconversion Rate at Month 24 | 78 Participants |
Secondary
Anti-HBs Seroconversion Rate at Month 30
Time frame: Month 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Anti-HBs Seroconversion Rate at Month 30 | 48 Participants |
| IM 60μg Group | Anti-HBs Seroconversion Rate at Month 30 | 62 Participants |
Secondary
Anti-HBs Seroconversion Rate at Month 36
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Anti-HBs Seroconversion Rate at Month 36 | 41 Participants |
| IM 60μg Group | Anti-HBs Seroconversion Rate at Month 36 | 51 Participants |
Secondary
Anti-HBs Seroconversion Rate at Month 42
Time frame: Month 42
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Anti-HBs Seroconversion Rate at Month 42 | 33 Participants |
| IM 60μg Group | Anti-HBs Seroconversion Rate at Month 42 | 40 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
| 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 |
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | Occurrence of Adverse Events After Vaccination | 14 Participants |
| IM 60μg Group | Occurrence of Adverse Events After Vaccination | 14 Participants |
Other Pre-specified
High-level Response Rate at Month 12
Time frame: Month 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | High-level Response Rate at Month 12 | 67 Participants |
| IM 60μg Group | High-level Response Rate at Month 12 | 82 Participants |
Other Pre-specified
High-level Response Rate at Month 18
Time frame: Month 18
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | High-level Response Rate at Month 18 | 30 Participants |
| IM 60μg Group | High-level Response Rate at Month 18 | 38 Participants |
Other Pre-specified
High-level Response Rate at Month 24
Time frame: Month 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | High-level Response Rate at Month 24 | 19 Participants |
| IM 60μg Group | High-level Response Rate at Month 24 | 23 Participants |
Other Pre-specified
High-level Response Rate at Month 30
Time frame: Month 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | High-level Response Rate at Month 30 | 15 Participants |
| IM 60μg Group | High-level Response Rate at Month 30 | 19 Participants |
Other Pre-specified
High-level Response Rate at Month 36
Time frame: Month 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | High-level Response Rate at Month 36 | 14 Participants |
| IM 60μg Group | High-level Response Rate at Month 36 | 14 Participants |
Other Pre-specified
High-level Response Rate at Month 42
Time frame: Month 42
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | High-level Response Rate at Month 42 | 8 Participants |
| IM 60μg Group | High-level Response Rate at Month 42 | 10 Participants |
Other Pre-specified
High-level Response Rate at Month 7
Time frame: Month 7
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IM 20μg Group | High-level Response Rate at Month 7 | 88 Participants |
| IM 60μg Group | High-level Response Rate at Month 7 | 107 Participants |