Hepatitis B
Conditions
Brief summary
This study was conducted in healthy infants and will provide new immunogenicity and safety data for the modified process hepatitis B vaccine. This study was conducted to address the following: to evaluate the immunogenicity and safety data of the 5 microgram dose of the modified process hepatitis B vaccine compared with a 10 microgram dose of the modified process hepatitis B vaccine, to evaluate another dosing schedule of 2, 4, and 6 months, and to provide descriptive immunogenicity data of another marketed vaccine (ENGERIX-B®).
Interventions
BIOLOGICALModified Process Hepatitis B Vaccine (Experimental)
Modified Process Hepatitis B Vaccine given intramuscularly (IM) in 3 injections of 5 ug (micrograms)/0.5 mL each over 4 months (Modified Process Hepatitis B vaccine 5 μg arm). Modified Process Hepatitis B Vaccine given IM in 3 Injections of 10 ug (micrograms)/0.5 mL each over 4 months (Modified Process Hepatitis B vaccine 10 μg arm).
BIOLOGICALHepatitis B Vaccine (Recombinant)
RECOMBIVAX HB™ (currently licensed product) given IM in 3 Injections of 5 ug/0.5 mL each over 4 months.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Months to 2 Months
Healthy volunteers
Yes
Inclusion criteria
* Participant is a healthy infant approximately 2 months of age
Exclusion criteria
* Birth mother is a known carrier of hepatitis B virus or another known carrier has lived in close contact with the participant * Participant's birth mother did not receive any prenatal care * Participant has previous history of hepatitis B infection * Participant has been vaccinated against hepatitis B or birth mother was vaccinated within 6 months before birth of participant * Participant has had a fever within 72 hours of study start * Participant has received any blood-derived product or birth mother received blood-derived product within 6 months of birth of participant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Seroresponders to the Modified Process Hepatitis B Vaccine (5 μg and 10 μg Dose), RECOMBIVAX HB™ Hepatitis B Vaccine (Currently Licensed Vaccine), and ENGERIX-B® | 7 months of age (1 month after 3 doses) | The percentage of participants as measured by Seroresponse. Seroresponse was defined as anti-hepatitis B surface antibodies greater than or equal to 10 milli-International Units (mIU)/mL. Success on the primary immunogenicity hypothesis required demonstrating an adequate anti-HBs seroprotection rate response for either modified process hepatitis B 5 μg vaccine or RECOMBIVAX HB™. Specifically, the lower bound of the multiplicity adjusted 95% confidence interval (CI) on the seroprotection rate for either vaccine was required to be above 90.0%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antibody to Hepatitis B Surface Antigen Geometric Mean Titer (Anti-HBs GMT) Responses for Modified Process Vaccine (5 μg and 10 μg), RECOMBIVAX™ Hepatitis B (Currently Licensed Vaccine), and ENGERIX-B® | 7 months of age (1 month after 3 doses) | Geometric Mean Titer - Antibody titer is a laboratory test that measures the presence and amount of antibodies in blood. |
Participant flow
Recruitment details
15-Nov-2006 (First Participant Enrolled in Study) to 24-Oct-2007 (Last Participant had their Last Visit). Last participant completed follow-up: 16-Oct-2007.This study was conducted at 15 sites; 14 in Finland and 1 in Norway.
Participants by arm
| Arm | Count |
|---|---|
| Modified Process Hepatitis B Vaccine 5 µg (Micrograms) Infants received a primary series of 3 doses of experimental vaccine (5 μg per dose) at 2, 4 and 6 months of age. | 431 |
| RECOMBIVAX™ Hepatitis B Vaccine Infants received a primary series of 3 doses of currently licensed vaccine (5 μg per dose) at 2, 4 and 6 months of age. | 427 |
| Modified Process Hepatitis B Vaccine 10 µg Infants received a primary series of 3 doses of experimental vaccine (10 μg per dose) at 2, 4 and 6 months of age. | 429 |
| ENGERIX-B® Infants received a primary series of 3 doses of currently licensed vaccine (10 μg per dose) at 2, 4 and 6 months of age. | 431 |
| Total | 1,718 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 2 | 1 | 1 |
| Overall Study | Subject discontinued for other reason | 1 | 2 | 2 | 1 |
| Overall Study | Subject Moved | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 3 | 2 | 4 |
Baseline characteristics
| Characteristic | Modified Process Hepatitis B Vaccine 5 µg (Micrograms) | RECOMBIVAX™ Hepatitis B Vaccine | Modified Process Hepatitis B Vaccine 10 µg | ENGERIX-B® | Total |
|---|---|---|---|---|---|
| Age, Continuous | 63.2 days STANDARD_DEVIATION 10.18 | 62.9 days STANDARD_DEVIATION 10.15 | 63.3 days STANDARD_DEVIATION 9.83 | 62.8 days STANDARD_DEVIATION 9.81 | 63.1 days STANDARD_DEVIATION 9.99 |
| Sex: Female, Male Female | 190 Participants | 217 Participants | 208 Participants | 201 Participants | 816 Participants |
| Sex: Female, Male Male | 241 Participants | 210 Participants | 221 Participants | 230 Participants | 902 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 308 / 430 | 294 / 424 | 276 / 429 | 288 / 428 |
| serious Total, serious adverse events | 11 / 430 | 2 / 424 | 6 / 429 | 8 / 428 |
Outcome results
Primary
The Percentage of Seroresponders to the Modified Process Hepatitis B Vaccine (5 μg and 10 μg Dose), RECOMBIVAX HB™ Hepatitis B Vaccine (Currently Licensed Vaccine), and ENGERIX-B®
The percentage of participants as measured by Seroresponse. Seroresponse was defined as anti-hepatitis B surface antibodies greater than or equal to 10 milli-International Units (mIU)/mL. Success on the primary immunogenicity hypothesis required demonstrating an adequate anti-HBs seroprotection rate response for either modified process hepatitis B 5 μg vaccine or RECOMBIVAX HB™. Specifically, the lower bound of the multiplicity adjusted 95% confidence interval (CI) on the seroprotection rate for either vaccine was required to be above 90.0%.
Time frame: 7 months of age (1 month after 3 doses)
Population: Participants who follow the protocol, do not have major protocol deviations and have post-vaccination serology within specified day ranges.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Process Hepatitis B Vaccine 5 µg (Micrograms) | The Percentage of Seroresponders to the Modified Process Hepatitis B Vaccine (5 μg and 10 μg Dose), RECOMBIVAX HB™ Hepatitis B Vaccine (Currently Licensed Vaccine), and ENGERIX-B® | 99.3 Percentage of participants |
| RECOMBIVAX™ Hepatitis B Vaccine | The Percentage of Seroresponders to the Modified Process Hepatitis B Vaccine (5 μg and 10 μg Dose), RECOMBIVAX HB™ Hepatitis B Vaccine (Currently Licensed Vaccine), and ENGERIX-B® | 98.5 Percentage of participants |
| Modified Process Hepatitis B Vaccine 10 µg | The Percentage of Seroresponders to the Modified Process Hepatitis B Vaccine (5 μg and 10 μg Dose), RECOMBIVAX HB™ Hepatitis B Vaccine (Currently Licensed Vaccine), and ENGERIX-B® | 100 Percentage of participants |
| ENGERIX-B® | The Percentage of Seroresponders to the Modified Process Hepatitis B Vaccine (5 μg and 10 μg Dose), RECOMBIVAX HB™ Hepatitis B Vaccine (Currently Licensed Vaccine), and ENGERIX-B® | 99.5 Percentage of participants |
Secondary
Antibody to Hepatitis B Surface Antigen Geometric Mean Titer (Anti-HBs GMT) Responses for Modified Process Vaccine (5 μg and 10 μg), RECOMBIVAX™ Hepatitis B (Currently Licensed Vaccine), and ENGERIX-B®
Geometric Mean Titer - Antibody titer is a laboratory test that measures the presence and amount of antibodies in blood.
Time frame: 7 months of age (1 month after 3 doses)
Population: Participants who follow the protocol, do not have major protocol deviations and have post-vaccination serology within specified day ranges.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Modified Process Hepatitis B Vaccine 5 µg (Micrograms) | Antibody to Hepatitis B Surface Antigen Geometric Mean Titer (Anti-HBs GMT) Responses for Modified Process Vaccine (5 μg and 10 μg), RECOMBIVAX™ Hepatitis B (Currently Licensed Vaccine), and ENGERIX-B® | 748.2 mIU/mL |
| RECOMBIVAX™ Hepatitis B Vaccine | Antibody to Hepatitis B Surface Antigen Geometric Mean Titer (Anti-HBs GMT) Responses for Modified Process Vaccine (5 μg and 10 μg), RECOMBIVAX™ Hepatitis B (Currently Licensed Vaccine), and ENGERIX-B® | 376.8 mIU/mL |
| Modified Process Hepatitis B Vaccine 10 µg | Antibody to Hepatitis B Surface Antigen Geometric Mean Titer (Anti-HBs GMT) Responses for Modified Process Vaccine (5 μg and 10 μg), RECOMBIVAX™ Hepatitis B (Currently Licensed Vaccine), and ENGERIX-B® | 981.5 mIU/mL |
| ENGERIX-B® | Antibody to Hepatitis B Surface Antigen Geometric Mean Titer (Anti-HBs GMT) Responses for Modified Process Vaccine (5 μg and 10 μg), RECOMBIVAX™ Hepatitis B (Currently Licensed Vaccine), and ENGERIX-B® | 556.6 mIU/mL |
Comparison: Comparison of Induced (effected) Geometric Mean Titer for the Modified Hepatitis B Process Vaccine and RECOMBIVAX Hepatitis B vaccine.95% CI: [1.69, 2.35]