Hepatitis B Virus Infection
Conditions
Keywords
hepatitis B virus
Brief summary
To describe the immunogenicity and safety of modified process hepatitis B vaccine administered to renal predialysis and dialysis patients
Interventions
Modified process hepatitis B vaccine 40 ug/1.0 mL injection in a 4 dose regimen at months 0, 1, 6, and 8. Duration of treatment is 9 months.
BIOLOGICALComparator: ENGERIX-B™
ENGERIX-B™ two 20 ug/1.0 mL injections in a 4 dose regimen at months 0, 1, 6, and 8. Duration of treatment is 9 months.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female subjects at least 18 years of age * Laboratory confirmed negative serology result to HbsAg (hepatitis b virus), anti-HBs (antibody to hepatitis B surface antigen), and anti HBc (antibody to hepatitis B core antigen) within 6 weeks of the initial dose of study vaccine * Patient on renal dialysis or a pre-dialysis patient with a creatinine clearance of \<=30 ml/min
Exclusion criteria
* Previous hepatitis B infection, vaccination with any hepatitis B vaccine * Recent febrile illness; hypersensitivity to any component of licensed hepatitis B vaccines * Recent administration of immune globulin, licensed inactivated vaccine within 14 days or licensed live vaccine within 30 days prior to receipt of first study vaccine * Receipt of investigational drugs or investigational vaccines within 3 months prior * Impairment of immunologic function * Recent use of systemic immunomodulatory medications * Pregnant women, nursing mothers or women planning to become pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Seroprotected Participants to the Modified Process Hepatitis B Vaccine and ENGERIX-B™ (Currently Licensed Vaccine) at Month 7 | 7 months (1 month after the third dose) | 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 dose) and at Month 7 (1 month after the third dose). |
| The Number of Seroprotected Participants to the Modified Process Hepatitis B Vaccine and ENGERIX-B™ (Currently Licensed Vaccine) at Month 9 | 9 months (1 month after the fourth dose) | 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 dose) and at Month 9 (1 month after the fourth dose). |
| The Total Number of Participants With One or More Injection-Site Adverse Experiences | Days 1-15 After Any Vaccination | — |
| The Total Number of Participants With a Maximum Temperature >= 100.0F / 37.8C | Days 1-5 After Any Vaccination | — |
| The Total Number of Participants With Serious Vaccine-Related Clinical Adverse Experiences | 0-9 months (recorded from first dose until the participant completes or discontinues the study) | Participants with adverse experiences considered possibly, probably, or definitely related to study vaccines and considered serious (death, persistent disability, life threatening, hospitalization, birth defects, cancer, or overdose). |
Participant flow
Recruitment details
22-Dec-2006 (First Patient Enrolled in Study) to 05-May-2008 (Last Participant had their Last Visit). This study was conducted at 23 sites: 7 in Canada, 8 in the United Kingdom, 5 in Italy, and 3 in Spain. In the Modified Process group, one participant was randomized by mistake, and therefore was not vaccinated.
Pre-assignment details
A screening serum sample was obtained prior to study entry and assayed for hepatitis B serologic markers. Only patients that were seronegative were considered for enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Modified Process Hepatitis B Vaccine Modified Process Hepatitis B Vaccine, 40 µg(micrograms) | 138 |
| ENGERIX-B™ ENGERIX-B™, 2 x 20 µg(micrograms) | 138 |
| Total | 276 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 5 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 11 | 7 |
| Overall Study | Randomized by mistake | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 6 |
Baseline characteristics
| Characteristic | Modified Process Hepatitis B Vaccine | ENGERIX-B™ | Total |
|---|---|---|---|
| Age, Continuous | 69.7 Years STANDARD_DEVIATION 13.4 | 69.2 Years STANDARD_DEVIATION 12.7 | 69.5 Years STANDARD_DEVIATION 13 |
| Sex: Female, Male Female | 53 Participants | 56 Participants | 109 Participants |
| Sex: Female, Male Male | 85 Participants | 82 Participants | 167 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 56 / — | 73 / — |
| serious Total, serious adverse events | 11 / — | 11 / — |
Outcome results
Primary
The Number of Seroprotected Participants to the Modified Process Hepatitis B Vaccine and ENGERIX-B™ (Currently Licensed Vaccine) at Month 7
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 dose) and at Month 7 (1 month after the third dose).
Time frame: 7 months (1 month after the third dose)
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 Seroprotected Participants to the Modified Process Hepatitis B Vaccine and ENGERIX-B™ (Currently Licensed Vaccine) at Month 7 | 49 Participants |
| ENGERIX-B™ | The Number of Seroprotected Participants to the Modified Process Hepatitis B Vaccine and ENGERIX-B™ (Currently Licensed Vaccine) at Month 7 | 64 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 after the third dose among subjects who were seronegative at baseline95% CI: [38.4, 58.7]
95% CI: [47.9, 67]
Primary
The Number of Seroprotected Participants to the Modified Process Hepatitis B Vaccine and ENGERIX-B™ (Currently Licensed Vaccine) at Month 9
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 dose) and at Month 9 (1 month after the fourth dose).
Time frame: 9 months (1 month after the fourth dose)
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 Seroprotected Participants to the Modified Process Hepatitis B Vaccine and ENGERIX-B™ (Currently Licensed Vaccine) at Month 9 | 66 Participants |
| ENGERIX-B™ | The Number of Seroprotected Participants to the Modified Process Hepatitis B Vaccine and ENGERIX-B™ (Currently Licensed Vaccine) at Month 9 | 72 Participants |
95% CI: [56.5, 75.8]
95% CI: [59.4, 77.9]
Primary
The Total Number of Participants With a Maximum Temperature >= 100.0F / 37.8C
Time frame: Days 1-5 After Any Vaccination
Population: Safety Analysis Set: The Safety Analysis Set is defined as all participants who receive 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 | 5 Participants |
| ENGERIX-B™ | The Total Number of Participants With a Maximum Temperature >= 100.0F / 37.8C | 6 Participants |
Primary
The Total Number of Participants With One or More Injection-Site Adverse Experiences
Time frame: Days 1-15 After Any Vaccination
Population: Safety Analysis Set: The Safety Analysis Set is defined as all participants who receive 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 | 43 Participants |
| ENGERIX-B™ | The Total Number of Participants With One or More Injection-Site Adverse Experiences | 48 Participants |
Primary
The Total Number of Participants With Serious Vaccine-Related Clinical Adverse Experiences
Participants with adverse experiences considered possibly, probably, or definitely related to study vaccines and considered serious (death, persistent disability, life threatening, hospitalization, birth defects, cancer, or overdose).
Time frame: 0-9 months (recorded from first dose until the participant completes or discontinues the study)
Population: Safety Analysis Set: The Safety Analysis Set is defined as all participants who receive 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 |
| ENGERIX-B™ | The Total Number of Participants With Serious Vaccine-Related Clinical Adverse Experiences | 0 Participants |