Hepatitis B Vaccine
Conditions
Keywords
Hepatitis B, Vaccine, Randomized Controlled Trial, HIV, Immunogenicity
Brief summary
Uptake, adherence, and completion of vaccination among HIV-infected adults were low, and their immune function and immune response to hepatitis B vaccination were also suboptimal, indicating that the current practice of hepatitis B vaccination can't protect HIV-infected adults from HBV infection. And the persistence of immunity induced by hepatitis B vaccination remains a challenge. This is a randomized, open-label trial, conducted among HIV-infected adults with drug rehabilitation. This study will compare the immunogenicity, immune persistence, and safety of three intramuscular 20µg and 60µg recombinant hepatitis B vaccines at months 0, 1, and 6 among HIV-infected adults.
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
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* HIV-infected * Aged between 18 and 70 years * 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 before or during the month preceding enrollment * Any Intolerance or allergy to any component of the vaccine * Ongoing opportunistic infection * Hematological disorder * Cancer * Unexplained fever the week before enrollment * Immunosuppressive or immunomodulating treatment in the last six months * Liver disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage 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 |
|---|---|---|
| Anti-HBs Concentration at Month 7 | Month 7 | The measurements of anti-HBs antibodies were determined quantitatively by CMIA(Chemiluminescent Microparticle Immunoassay ). |
| Number and Percentage 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 12 | Month 12 | The measurements of anti-HBs antibodies were determined quantitatively by CMIA（Chemiluminescent Microparticle Immunoassay）. |
| 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 |
| Serious Adverse Events (SAE) Occurred During 42 Month | Month 0-42 | Occurrence of Serious adverse events (SAE) within 42 month after vaccination with the hepatitis B |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage 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. |
| Number and Percentage 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 Percentage of Participants With Anti-HBs Antibodies at Month 6 Before the Third Injection | Month 6 before the third injection | The measurements of anti-HBs antibodies were determined quantitatively by CMIA. The accepted protective serum anti-HBs level was ≥10 mIU/ml. |
| Anti-HBs Concentration at Month 6 Before the Third Injection | Month 6 before the third injection | Anti-HBs concentration at month 6 before the third injection as measured by CMIA（Chemiluminescent Microparticle Immunoassay）. |
| Number and Percentage of Participants With Anti-HBs High-level Response at Month 6 Before the Third Injection | Month 6 before the third injection | The measurements of anti-HBs antibodies were determined quantitatively by CMIA. and anti-HBs concentrations ≥100 mIU/ml were high-level response. |
| Number and Percentage 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 60 µg Dose Hepatitis B Vaccine 60 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6
60 µg dose hepatitis B vaccine: three-dose, 60 µg per dose | 91 |
| 20 µg Dose Hepatitis B Vaccine 20 µg recombinant hepatitis B vaccine with three injections at months 0, 1, and 6
20 µg dose hepatitis B vaccine: three-dose, 20 µg per dose | 91 |
| Total | 182 |
Baseline characteristics
| Characteristic | 60 µg Dose Hepatitis B Vaccine | 20 µg Dose Hepatitis B Vaccine | Total |
|---|---|---|---|
| Age, Continuous | 40.5 years STANDARD_DEVIATION 11.4 | 38.2 years STANDARD_DEVIATION 10.6 | 39.3 years STANDARD_DEVIATION 11.1 |
| Race/Ethnicity, Customized Han ethnicity | 32 Participants | 24 Participants | 56 Participants |
| Race/Ethnicity, Customized others | 10 Participants | 5 Participants | 15 Participants |
| Race/Ethnicity, Customized Zhuang ethnicity | 49 Participants | 62 Participants | 111 Participants |
| Sex: Female, Male Female | 42 Participants | 33 Participants | 75 Participants |
| Sex: Female, Male Male | 49 Participants | 58 Participants | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 88 | 0 / 88 |
| other Total, other adverse events | 8 / 88 | 6 / 88 |
| serious Total, serious adverse events | 0 / 88 | 0 / 88 |
Outcome results
Primary
Number and Percentage 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: 83 and 82 patients in the IM60（60μg recombinant hepatitis B vaccine） and IM20（20μg recombinant hepatitis B vaccine） groups completed the followed-up at months 7.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 60 µg Dose Hepatitis B Vaccine | Number and Percentage of Participants With Anti-HBs Seroconversion at Month 7 | 75 Participants |
| 20 µg Dose Hepatitis B Vaccine | Number and Percentage of Participants With Anti-HBs Seroconversion at Month 7 | 69 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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 60 µg Dose Hepatitis B Vaccine | Anti-HBs Concentration at Month 12 | 290.4 mIU/ml |
| 20 µg Dose Hepatitis B Vaccine | Anti-HBs Concentration at Month 12 | 264.4 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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 60 µg Dose Hepatitis B Vaccine | Anti-HBs Concentration at Month 7 | 623.3 mIU/mL |
| 20 µg Dose Hepatitis B Vaccine | Anti-HBs Concentration at Month 7 | 469.4 mIU/mL |
Secondary
Number and Percentage 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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 60 µg Dose Hepatitis B Vaccine | Number and Percentage of Participants With Anti-HBs Seroconversion at Month 12 | 55 Participants |
| 20 µg Dose Hepatitis B Vaccine | Number and Percentage of Participants With Anti-HBs Seroconversion at Month 12 | 50 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 | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 60 µg Dose Hepatitis B Vaccine | Occurrence of Adverse Events After Vaccination | pain | 5 Participants |
| 60 µg Dose Hepatitis B Vaccine | Occurrence of Adverse Events After Vaccination | erythema | 6 Participants |
| 60 µg Dose Hepatitis B Vaccine | Occurrence of Adverse Events After Vaccination | edema | 5 Participants |
| 60 µg Dose Hepatitis B Vaccine | Occurrence of Adverse Events After Vaccination | induration | 4 Participants |
| 20 µg Dose Hepatitis B Vaccine | Occurrence of Adverse Events After Vaccination | induration | 4 Participants |
| 20 µg Dose Hepatitis B Vaccine | Occurrence of Adverse Events After Vaccination | pain | 5 Participants |
| 20 µg Dose Hepatitis B Vaccine | Occurrence of Adverse Events After Vaccination | edema | 4 Participants |
| 20 µg Dose Hepatitis B Vaccine | Occurrence of Adverse Events After Vaccination | erythema | 5 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 vaccination
Population: Safety analysis was performed on all included participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 60 µg Dose Hepatitis B Vaccine | Occurrence of Adverse Events After Vaccination | fever | 1 participants |
| 60 µg Dose Hepatitis B Vaccine | Occurrence of Adverse Events After Vaccination | headache | 2 participants |
| 20 µg Dose Hepatitis B Vaccine | Occurrence of Adverse Events After Vaccination | fever | 1 participants |
| 20 µg Dose Hepatitis B Vaccine | Occurrence of Adverse Events After Vaccination | headache | 1 participants |
Secondary
Serious Adverse Events (SAE) Occurred During 42 Month
Occurrence of Serious adverse events (SAE) within 42 month after vaccination with the hepatitis B
Time frame: Month 0-42
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 60 µg Dose Hepatitis B Vaccine | Serious Adverse Events (SAE) Occurred During 42 Month | 0 Participants |
| 20 µg Dose Hepatitis B Vaccine | Serious Adverse Events (SAE) Occurred During 42 Month | 0 Participants |
Other Pre-specified
Anti-HBs Concentration at Month 6 Before the Third Injection
Anti-HBs concentration at month 6 before the third injection as measured by CMIA（Chemiluminescent Microparticle Immunoassay）.
Time frame: Month 6 before the third injection
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 60 µg Dose Hepatitis B Vaccine | Anti-HBs Concentration at Month 6 Before the Third Injection | 148.9 mIU/ml |
| 20 µg Dose Hepatitis B Vaccine | Anti-HBs Concentration at Month 6 Before the Third Injection | 130.6 mIU/ml |
Other Pre-specified
Number and Percentage of Participants With Anti-HBs Antibodies at Month 6 Before the Third Injection
The measurements of anti-HBs antibodies were determined quantitatively by CMIA. The accepted protective serum anti-HBs level was ≥10 mIU/ml.
Time frame: Month 6 before the third injection
Population: 83 and 70 patients in the IM60 and IM20 groups completed the followed-up at month 6 before the third injection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 60 µg Dose Hepatitis B Vaccine | Number and Percentage of Participants With Anti-HBs Antibodies at Month 6 Before the Third Injection | 65 Participants |
| 20 µg Dose Hepatitis B Vaccine | Number and Percentage of Participants With Anti-HBs Antibodies at Month 6 Before the Third Injection | 61 Participants |
Other Pre-specified
Number and Percentage 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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 60 µg Dose Hepatitis B Vaccine | Number and Percentage of Participants With Anti-HBs High-level Response at Month 12 | 34 Participants |
| 20 µg Dose Hepatitis B Vaccine | Number and Percentage of Participants With Anti-HBs High-level Response at Month 12 | 26 Participants |
Other Pre-specified
Number and Percentage of Participants With Anti-HBs High-level Response at Month 6 Before the Third Injection
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 6 before the third injection
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 60 µg Dose Hepatitis B Vaccine | Number and Percentage of Participants With Anti-HBs High-level Response at Month 6 Before the Third Injection | 29 Participants |
| 20 µg Dose Hepatitis B Vaccine | Number and Percentage of Participants With Anti-HBs High-level Response at Month 6 Before the Third Injection | 27 Participants |
Other Pre-specified
Number and Percentage 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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 60 µg Dose Hepatitis B Vaccine | Number and Percentage of Participants With Anti-HBs High-level Response at Month 7 | 62 Participants |
| 20 µg Dose Hepatitis B Vaccine | Number and Percentage of Participants With Anti-HBs High-level Response at Month 7 | 54 Participants |
Other Pre-specified
Number and Percentage 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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 60 µg Dose Hepatitis B Vaccine | Number and Percentage of Participants With Anti-HBs Seroconversion at Month 42 | 31 Participants |
| 20 µg Dose Hepatitis B Vaccine | Number and Percentage of Participants With Anti-HBs Seroconversion at Month 42 | 29 Participants |