Hepatitis B
Conditions
Brief summary
To assess the safety and immunogenicity of a booster dose of hepatitis B vaccine in children who have received a 3-dose primary series of either RECOMBIVAX HB or ENGERIX-B. The primary vaccination series (was given 4 to 8 years prior to study entry and consisted of a licensed hepatitis B vaccine product (either RECOMBIVAX HB or ENGERIX-B). The booster dose given in this study will be either an investigational Merck product (Modified Process Hepatitis B Vaccine) or licensed ENGERIX-B vaccine.
Interventions
Single dose 5 µg/0.5ml modified process hepatitis B vaccine
BIOLOGICALComparator: Comparator: ENGERIX-B
Single dose 10 µg/0.5ml ENGERIX-B
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
4 Years to 8 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy Children 4 to 8 years of age * Complete medical records documenting receiving a previous hepatitis B vaccination during the first year of life (for Cohort A and B only) * Complete 3-dose vaccination with either a primary series of RECOMBIVAX HB or a primary series of ENGERIX-B (for Cohort A and B only)
Exclusion criteria
* Birth mother known to be a carrier of hepatitis B virus (Cohort C only) * History of previous hepatitis B vaccine * History of vaccination with any hepatitis B vaccine (Cohort C only) * Known of suspected hypersensitivity to any component of RECOMBIVAX HB or ENGERIX-B (eg aluminum, yeast) recent administration of hepatitis B immune globulin (HBIg), serum immune globulin, or any other blood-derived product * Receipt of investigational drugs or vaccines within 3 months prior to study vaccine or planned within study period * Impairment of immunologic function or recent use of immunomodulatory medications * A Combination of different hepatitis B vaccines used in the primary vaccination series (Cohort A and B only)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Antibody Response to Hepatitis B Surface Antigen in Subjects Who Received a 3-dose Primary Series of RECOMBIVAX HB in Infancy | 4 weeks after vaccination with either modified process hepatitis B vaccine or ENGERIX-B | Number of subjects who received a 3-dose primary series of RECOMBIVAX HB™ in infancy and who demonstrated antibodies to hepatitis B surface antigen ≥10 mIU/mL at 4 weeks after receiving a booster dose of modified process hepatitis B vaccine or ENGERIX-B™. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antibody Response to Hepatitis B Surface Antigen in Subjects Who Received a 3-dose Primary Series of ENGERIX-B in Infancy | 4 weeks after vaccination with either modified process hepatitis B vaccine or ENGERIX-B | Number of subjects who received a 3-dose primary series of ENGERIX-B ™ in infancy and who demonstrated antibodies to hepatitis B surface antigen ≥10 mIU/mL at 4 weeks after receiving a booster dose of modified process hepatitis B vaccine or ENGERIX-B™. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Antibody Response to Hepatitis B Surface Antigen in Subjects Who Received a 3-dose Primary Series of RECOMBIVAX HB in Infancy | 4 weeks after vaccination with either modified process hepatitis B vaccine or ENGERIX-B | Geometric Mean Titer (GMT) for all subjects who completed a 3-dose primary vaccination series of RECOMBIVAX HB™ and who received a booster dose of either modified process hepatitis B vaccine or ENGERIX-B™ |
| Antibody Response to Hepatitis B Surface Antigen in Subjects Who Received a 3-dose Primary Series of ENGERIX-B in Infancy | 4 weeks after vaccination with either modified process hepatitis B vaccine or ENGERIX-B | Geometric Mean Titer (GMT) for all subjects who completed a 3-dose primary vaccination series of ENGERIX-B™ and who received a booster dose of either modified process hepatitis B vaccine or ENGERIX-B™ |
Participant flow
Recruitment details
This study was conducted at 77 primary study sites in Spain and 1 study site in Canada. Date of first subject visit: 26-Sep-2006; Date of last subject visit: 23-June-2008
Pre-assignment details
To be eligible for enrollment in the study, participants were to have received a primary series of 3 doses of the same type of hepatitis B vaccine (either RECOMBIVAX HB or ENGERIX-B) during the first year of life.
Participants by arm
| Arm | Count |
|---|---|
| Modified Process Hepatitis B Vaccine Booster (Group 1) Participants received a primary series of 3 doses of RECOMBIVAX HB™ (5 µg (micrograms) per dose) during the first year of life outside of the context of the study; During the study, participants received one dose of Modified Process Hepatitis B Vaccine, 5 µg (micrograms) (Booster Dose) | 376 |
| ENGERIX-B™ Booster (RECOMBIVAX-HB™ in Infancy) (Group 2) Participants received a primary series of 3 doses of RECOMBIVAX HB™ (5 µg (micrograms) per dose) during the first year of life outside of the context of the study; During the study, participants received one dose of ENGERIX-B™ (10 µg (micrograms) per dose) (Booster Dose) | 375 |
| Modified Process Hepatitis B Vaccine Booster (Group 3) Participants received a primary series of 3 doses of ENGERIX-B™ (10 µg (micrograms) per dose).during the first year of life outside of the context of the study; During the study, participants received one dose of Modified Process Hepatitis B Vaccine, 5 µg (micrograms) (Booster Dose) | 353 |
| ENGERIX-B™ Booster (ENGERIX-B™ in Infancy) (Group 4) Participants received a primary series of 3 doses of ENGERIX-B™ (10 µg (micrograms) per dose).during the first year of life outside of the context of the study; During the study, participants received one dose of ENGERIX-B™ (10 µg (micrograms) per dose) (Booster Dose) | 354 |
| Modified Process Hepatitis B Vaccine (Group 5) Participants did not receive a prior vaccination with a hepatitis B vaccine; During the study, participants received one dose of Modified Process Hepatitis B Vaccine, 5 µg (micrograms) | 20 |
| Total | 1,478 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Difficulties in specimen collection | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 2 | 1 |
| Overall Study | Protocol Violation | 6 | 2 | 0 | 1 | 0 |
| Overall Study | Vaccine supply issue | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 7 | 2 | 3 | 0 |
Baseline characteristics
| Characteristic | Modified Process Hepatitis B Vaccine Booster (Group 1) | ENGERIX-B™ Booster (RECOMBIVAX-HB™ in Infancy) (Group 2) | Modified Process Hepatitis B Vaccine Booster (Group 3) | ENGERIX-B™ Booster (ENGERIX-B™ in Infancy) (Group 4) | Modified Process Hepatitis B Vaccine (Group 5) | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 5.7 years STANDARD_DEVIATION 0.92 | 5.7 years STANDARD_DEVIATION 0.92 | 5.3 years STANDARD_DEVIATION 1.05 | 5.4 years STANDARD_DEVIATION 0.98 | 4.3 years STANDARD_DEVIATION 0.66 | 5.5 years STANDARD_DEVIATION 0.98 |
| Sex: Female, Male Female | 172 Participants | 186 Participants | 179 Participants | 161 Participants | 13 Participants | 711 Participants |
| Sex: Female, Male Male | 204 Participants | 189 Participants | 174 Participants | 193 Participants | 7 Participants | 767 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 214 / 369 | 192 / 368 | 198 / 344 | 194 / 342 | 9 / 19 |
| serious Total, serious adverse events | 0 / 369 | 0 / 368 | 0 / 344 | 2 / 342 | 0 / 19 |
Outcome results
Primary
Antibody Response to Hepatitis B Surface Antigen in Subjects Who Received a 3-dose Primary Series of RECOMBIVAX HB in Infancy
Number of subjects who received a 3-dose primary series of RECOMBIVAX HB™ in infancy and who demonstrated antibodies to hepatitis B surface antigen ≥10 mIU/mL at 4 weeks after receiving a booster dose of modified process hepatitis B vaccine or ENGERIX-B™.
Time frame: 4 weeks after vaccination with either modified process hepatitis B vaccine or ENGERIX-B
Population: Per-protocol population (defined as the subjects that completed the study as defined by the protocol). Subjects were excluded from the analysis population mainly because they did not receive the primary series vaccination series as defined in the protocol or the study vaccine was not maintained at proper temperature as defined in the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Process Hepatitis B Vaccine Booster (Group 1) | Antibody Response to Hepatitis B Surface Antigen in Subjects Who Received a 3-dose Primary Series of RECOMBIVAX HB in Infancy | 323 Participants |
| ENGERIX-B™ Booster (RECOMBIVAX-HB™ in Infancy) (Group 2) | Antibody Response to Hepatitis B Surface Antigen in Subjects Who Received a 3-dose Primary Series of RECOMBIVAX HB in Infancy | 305 Participants |
Comparison: The primary purpose of this study was to show that subjects who received a primary series of RECOMBIVAX HB™ in the first year of life were adequately protected by RECOMBIVAX HB™ by measuring the immune response to a single booster dose of either a modified process vaccine or ENGERIX-B™.p-value: <0.00195.2% CI: [92.1, 97.1]Hochberg's step up
Comparison: The primary purpose of this study was to show that subjects who received a primary series of RECOMBIVAX HB™ in the first year of life were adequately protected by RECOMBIVAX HB™ by measuring the immune response to a single booster dose of either a modified process vaccine or ENGERIX-B™.p-value: <0.00197.6% CI: [91.6, 97.3]Hochberg's step up
Comparison: The primary purpose of this study was to show that subjects who received a primary series of RECOMBIVAX HB™ in the first year of life were adequately protected by RECOMBIVAX HB™ by measuring the immune response to a single booster dose of either a modified process vaccine or ENGERIX-B™.p-value: 0.1995.2% CI: [88, 94.4]Hochberg's step up
Secondary
Antibody Response to Hepatitis B Surface Antigen in Subjects Who Received a 3-dose Primary Series of ENGERIX-B in Infancy
Number of subjects who received a 3-dose primary series of ENGERIX-B ™ in infancy and who demonstrated antibodies to hepatitis B surface antigen ≥10 mIU/mL at 4 weeks after receiving a booster dose of modified process hepatitis B vaccine or ENGERIX-B™.
Time frame: 4 weeks after vaccination with either modified process hepatitis B vaccine or ENGERIX-B
Population: Per-protocol population (defined as the subjects that completed the study as defined by the protocol). Subjects were excluded from the analysis population mainly because they did not receive the primary series vaccination series as defined in the protocol or the study vaccine was not maintained at proper temperature as defined in the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Process Hepatitis B Vaccine Booster (Group 1) | Antibody Response to Hepatitis B Surface Antigen in Subjects Who Received a 3-dose Primary Series of ENGERIX-B in Infancy | 329 Participants |
| ENGERIX-B™ Booster (RECOMBIVAX-HB™ in Infancy) (Group 2) | Antibody Response to Hepatitis B Surface Antigen in Subjects Who Received a 3-dose Primary Series of ENGERIX-B in Infancy | 313 Participants |
Comparison: The purpose of the secondary analysis is to demonstrate that there is an adequate SPR in subjects who received a primary vaccination series of ENGERIX-B™ and a booster dose of modified process hepatitis B vaccine. An adequate response requires the lower bound of the two-sided 95% confidence interval for the SPR to exceed 90%.95% CI: [95, 98.8]
Other Pre-specified
Antibody Response to Hepatitis B Surface Antigen in Subjects Who Received a 3-dose Primary Series of ENGERIX-B in Infancy
Geometric Mean Titer (GMT) for all subjects who completed a 3-dose primary vaccination series of ENGERIX-B™ and who received a booster dose of either modified process hepatitis B vaccine or ENGERIX-B™
Time frame: 4 weeks after vaccination with either modified process hepatitis B vaccine or ENGERIX-B
Population: Per-protocol population (defined as the subjects that completed the study as defined by the protocol). Subjects were excluded from the analysis population mainly because they did not receive the primary series vaccination series as defined in the protocol or the study vaccine was not maintained at proper temperature as defined in the protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Modified Process Hepatitis B Vaccine Booster (Group 1) | Antibody Response to Hepatitis B Surface Antigen in Subjects Who Received a 3-dose Primary Series of ENGERIX-B in Infancy | 1424.0 mIU/mL |
| ENGERIX-B™ Booster (RECOMBIVAX-HB™ in Infancy) (Group 2) | Antibody Response to Hepatitis B Surface Antigen in Subjects Who Received a 3-dose Primary Series of ENGERIX-B in Infancy | 1216.1 mIU/mL |
Other Pre-specified
Antibody Response to Hepatitis B Surface Antigen in Subjects Who Received a 3-dose Primary Series of RECOMBIVAX HB in Infancy
Geometric Mean Titer (GMT) for all subjects who completed a 3-dose primary vaccination series of RECOMBIVAX HB™ and who received a booster dose of either modified process hepatitis B vaccine or ENGERIX-B™
Time frame: 4 weeks after vaccination with either modified process hepatitis B vaccine or ENGERIX-B
Population: Per-protocol population (defined as the subjects that completed the study as defined by the protocol). Subjects were excluded from the analysis population mainly because they did not receive the primary series vaccination series as defined in the protocol or the study vaccine was not maintained at proper temperature as defined in the protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Modified Process Hepatitis B Vaccine Booster (Group 1) | Antibody Response to Hepatitis B Surface Antigen in Subjects Who Received a 3-dose Primary Series of RECOMBIVAX HB in Infancy | 476.9 mIU/mL |
| ENGERIX-B™ Booster (RECOMBIVAX-HB™ in Infancy) (Group 2) | Antibody Response to Hepatitis B Surface Antigen in Subjects Who Received a 3-dose Primary Series of RECOMBIVAX HB in Infancy | 561.2 mIU/mL |