Hepatitis B
Conditions
Brief summary
The purpose of this trial is to determine if there is an improvement in the immune response of older adults over 50 years of age using a modified process hepatitis B vaccine and a currently licensed hepatitis B vaccine (RECOMBIVAX HB™).
Interventions
BIOLOGICALComparator: RECOMBIVAX HB™ Hepatitis B Vaccine (Recombinant)
RECOMBIVAX HB™ (currently licensed product) given IM (Intramuscular) in 3 doses of 10 mcg (micrograms)/1.0 mL each over 6 months.
BIOLOGICALComparator: Modified Process Hepatitis B Vaccine (Experimental)
Modified Process Hepatitis B Vaccine (Experimental) given IM (Intramuscular) in 3 doses of 10 mcg (micrograms)/1.0 mL each over 6 months.
BIOLOGICALComparator: ENGERIX-B™ (currently licensed product)
ENGERIX-B™ given IM (Intramuscular) in 3 doses of 20 mcg (micrograms)/1.0 mL each over 6 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
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and female older adults greater than or equal to 50 years of age
Exclusion criteria
* Any adult with a history of previous hepatitis B infection * A history of vaccination with any hepatitis B vaccine * Recent (\<72 hours) history of febrile illness (oral temperature =37.8ºC/=100.0ºF) * Known or suspected hypersensitivity to any component of RECOMBIVAX HB™ or ENGERIX-B™ (e.g., aluminum, yeast) * Recent administration (within 3 months prior to first injection with the study vaccine) of hepatitis B immune globulin (HBIG), serum immune globulin, or any other blood-derived product * Receipt of licensed inactivated vaccines within 14 days prior to first injection with the study vaccine * Receipt of licensed live virus vaccines within the 30 days prior to injection with the study vaccine * Receipt of investigational drugs or other investigational vaccines within 3 months prior to first injection with the study vaccine * Known or suspected impairment of immunologic function or recent use of immunomodulatory medications (e.g., systemic corticosteroids). Does not include topical and inhaled steroids * Pregnant women, nursing mothers, and women planning to become pregnant within the study period * Any condition that, in the opinion of the investigator, might interfere with the evaluation of the study objectives
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Seroresponders to the Modified Process Hepatitis B Vaccine and RECOMBIVAX HB™ (Currently Licensed Vaccine) | 7 months (1 month after third vaccination) | The number of participants as measured by the seroprotection rate (anti-hepatitis B surface antibodies greater than or equal to 10 mIU/mL). Anti-HBs (Antibodies against hepatitis B surface antigen) titers were measured from blood samples taken at Day 1 (prior to the first vaccination) and at Month 7 (1 month after the third vaccination). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Seroresponders to ENGERIX-B™ (Currently Licensed Vaccine) | 7 months (1 month after third vaccination) | The number of participants as measured by the seroprotection rate (anti-hepatitis B surface antibodies greater than or equal to 10 mIU/mL). Anti-HBs (Antibodies against hepatitis B surface antigen) titers were measured from blood samples taken at Day 1 (prior to the first vaccination) and at Month 7 (1 month after the third vaccination). |
| The Total Number of Participants With One or More Injection-site Adverse Experiences | Days 1-5 After Any Vaccination | — |
| The Total Number of Participants With a Maximum Temperature >=100.0F/37.8C | Day 1-5 After Vaccination | — |
| The Total Number of Participants With Serious Vaccine-Related Clinical Adverse Experiences | During Entire Study Period (from first vaccination until the participant completes or discontinues: up to 7 months) | — |
Participant flow
Recruitment details
27-Nov-2006 (First Participant Enrolled in Study) to 26-Nov-2007 (Last Participant had their Last Visit). This study was conducted at 22 sites: 10 in Canada, 2 in Denmark, 5 in Sweden, and 5 in the United Kingdom.
Pre-assignment details
In the Modified Process group, 2 participants were randomized but not vaccinated: 1 participant withdrew consent, and 1 participant had an SAE (Serious Adverse Experience) of hypertension prior to vaccination.
Participants by arm
| Arm | Count |
|---|---|
| Modified Process Hepatitis B Vaccine Modified Process Hepatitis B Vaccine, 10 µg (micrograms) | 183 |
| RECOMBIVAX-HB™ RECOMBIVAX-HB™, 10 µg (micrograms) | 183 |
| ENGERIX-B™ ENGERIX-B™, 20 µg (micrograms) | 172 |
| Total | 538 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 2 |
| Overall Study | Lost to Follow-up | 4 | 3 | 5 |
| Overall Study | Protocol Violation | 1 | 2 | 0 |
| Overall Study | see pre-assignment details | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Modified Process Hepatitis B Vaccine | RECOMBIVAX-HB™ | ENGERIX-B™ | Total |
|---|---|---|---|---|
| Age, Continuous | 60.3 years STANDARD_DEVIATION 7.9 | 60.4 years STANDARD_DEVIATION 7.6 | 59.8 years STANDARD_DEVIATION 6.5 | 60.2 years STANDARD_DEVIATION 7.4 |
| Sex: Female, Male Female | 93 Participants | 94 Participants | 73 Participants | 260 Participants |
| Sex: Female, Male Male | 90 Participants | 89 Participants | 99 Participants | 278 Participants |
Outcome results
Primary
The Number of Seroresponders to the Modified Process Hepatitis B Vaccine and RECOMBIVAX HB™ (Currently Licensed Vaccine)
The number of participants as measured by the seroprotection rate (anti-hepatitis B surface antibodies greater than or equal to 10 mIU/mL). Anti-HBs (Antibodies against hepatitis B surface antigen) titers were measured from blood samples taken at Day 1 (prior to the first vaccination) and at Month 7 (1 month after the third vaccination).
Time frame: 7 months (1 month after third vaccination)
Population: Per-protocol Population. The Per-protocol Population is defined as the participants that were able to complete the study as defined by the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Process Hepatitis B Vaccine | The Number of Seroresponders to the Modified Process Hepatitis B Vaccine and RECOMBIVAX HB™ (Currently Licensed Vaccine) | 115 Participants |
| RECOMBIVAX-HB™ | The Number of Seroresponders to the Modified Process Hepatitis B Vaccine and RECOMBIVAX HB™ (Currently Licensed Vaccine) | 100 Participants |
Comparison: No hypothesis is being tested. The purpose of the primary analysis is to estimate the seroprotection rate (percentage of subjects with anti-HBs \>=10mIU/mL) in each group at 1 month post vaccination 3, among subjects who were seronegative at baseline.95% CI: [68, 82.2]
Comparison: No hypothesis is being tested. The purpose of the primary analysis is to estimate the seroprotection rate (percentage of subjects with anti-HBs \>=10mIU/mL) in each group at 1 month post vaccination 3, among subjects who were seronegative at baseline.95% CI: [59.8, 75.5]
Secondary
The Number of Seroresponders to ENGERIX-B™ (Currently Licensed Vaccine)
The number of participants as measured by the seroprotection rate (anti-hepatitis B surface antibodies greater than or equal to 10 mIU/mL). Anti-HBs (Antibodies against hepatitis B surface antigen) titers were measured from blood samples taken at Day 1 (prior to the first vaccination) and at Month 7 (1 month after the third vaccination).
Time frame: 7 months (1 month after third vaccination)
Population: Per-protocol Population. The Per-protocol Population is defined as the participants that were able to complete the study as defined by the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Process Hepatitis B Vaccine | The Number of Seroresponders to ENGERIX-B™ (Currently Licensed Vaccine) | 121 Participants |
Comparison: No hypothesis is being tested. The purpose of the secondary analysis is to estimate the seroprotection rate (percentage of subjects with anti-HBs \>=10mIU/mL) for ENGERIX-B™ at 1 month post vaccination 3, among subjects who were seronegative at baseline.95% CI: [77, 89.6]
Secondary
The Total Number of Participants With a Maximum Temperature >=100.0F/37.8C
Time frame: Day 1-5 After Vaccination
Population: Safety Analysis Set - defined as all participants who received at least one injection of vaccine and who had a safety follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Process Hepatitis B Vaccine | The Total Number of Participants With a Maximum Temperature >=100.0F/37.8C | 2 Participants |
| RECOMBIVAX-HB™ | The Total Number of Participants With a Maximum Temperature >=100.0F/37.8C | 3 Participants |
| ENGERIX-B™ | The Total Number of Participants With a Maximum Temperature >=100.0F/37.8C | 3 Participants |
Secondary
The Total Number of Participants With One or More Injection-site Adverse Experiences
Time frame: Days 1-5 After Any Vaccination
Population: Safety Analysis Set - defined as all participants who received at least one injection of vaccine and who had a safety follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Process Hepatitis B Vaccine | The Total Number of Participants With One or More Injection-site Adverse Experiences | 103 Participants |
| RECOMBIVAX-HB™ | The Total Number of Participants With One or More Injection-site Adverse Experiences | 115 Participants |
| ENGERIX-B™ | The Total Number of Participants With One or More Injection-site Adverse Experiences | 107 Participants |
Secondary
The Total Number of Participants With Serious Vaccine-Related Clinical Adverse Experiences
Time frame: During Entire Study Period (from first vaccination until the participant completes or discontinues: up to 7 months)
Population: Safety Analysis Set - defined as all participants who received at least one injection of vaccine and who had a safety follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modified Process Hepatitis B Vaccine | The Total Number of Participants With Serious Vaccine-Related Clinical Adverse Experiences | 0 Participants |
| RECOMBIVAX-HB™ | The Total Number of Participants With Serious Vaccine-Related Clinical Adverse Experiences | 0 Participants |
| ENGERIX-B™ | The Total Number of Participants With Serious Vaccine-Related Clinical Adverse Experiences | 0 Participants |