Haemophilus Influenzae Type B, Hepatitis B
Conditions
Keywords
Haemophilus Influenza, type b and Hepatitis B
Brief summary
To determine if there is an improvement in the immune response to HBsAg (hepatitis B virus) in healthy infants using a modified process in a combination Haemophilus Influenzae, type b/Hepatitis B vaccine and a currently licensed Haemophilus Influenzae, type b/Hepatitis B vaccine
Interventions
BIOLOGICALComparator: Modified Process Vaccine
Modified process vaccine HBsAg 5 ug/0.5 mL and PRP \[OMPC\] 7.5 ug/0.5 mL in a 3-dose regimen at 2, 4 & 12 months of age. Duration of treatment is 11 months.
BIOLOGICALComparator: COMVAX™
COMVAX™ HBsAg 5 ug/0.5 mL and PRP \[OMPC\] 7.5 ug/0.5 mL in a 3-dose regimen at 2, 4, and 12 months of age. Duration of treatment is 11 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
40 Days to 80 Days
Healthy volunteers
Yes
Inclusion criteria
* Healthy 2-month-old full term infants born to non-HBs Ag (hepatitis B virus) carrier mothers
Exclusion criteria
* Birth mother known to be a carrier of hepatitis B virus (HBsAg+) or known carriers ever living in close contact with the subject * History of previous hepatitis B infection; history of vaccination with any hepatitis B vaccine * Recent (\<72 hours) history of febrile illness (rectal temperature \>=38.1°C/\>=100.5°F) * Known or suspected hypersensitivity to any component of RECOMBIVAXHB™ or COMVAX™ (e.g., aluminum, yeast) * Recent administration (w/i 3 months prior to study start) of hepatitis B immune globulin (HBIg), serum immune globulin, or any other blood-derived product * Receipt of investigational drugs or investigational vaccines within 3 months prior to study start or if planned within the study period; * Known or suspected impairment of immunologic function or recent use (within 3 months prior to study start) of immunomodulatory medications (does not include topical and inhaled steroids); * Any condition that, in the opinion of the investigator, might interfere with the evaluation of study objectives; or inability to comply with the study schedule and/or inability to attend all required study visits
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Anti-HBs Seroprotected Participants 1 Month After the Third Dose. | 11 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 Month 11 (1 month after the third dose) |
| The Anti-HBs GMT (Geometric Mean Titer) 1 Month After the Third Dose. | 11 months (1 month after the third dose) | Geometric Mean Titer (GMT) - This is an Antibody titer that is measured using a laboratory test to detect the presence and amount of antibodies in a person's blood. Anti-HBs (Antibodies against hepatitis B surface antigen) and Geometric Mean Titers were measured from blood samples taken at Month 11 (1 month after the third dose). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Total Number of Participants With Serious Vaccine-Related Clinical Adverse Experiences | 0-11 months (recorded from first dose until the participant completes or discontinues) | 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) |
| The Number of Anti-PRP Seroprotected Participants 1 Month After the Third Dose. | 11 months (1 month after the third dose) | The number of participants as measured by the seroprotection rate (anti-polyribosylribitol phosphate antibodies greater than 1 µg/mL). Anti-PRP (Antibodies against polyribosylribitol phosphate) titers were measured from blood samples taken at Month 11 (1 month after the third dose) |
| The Anti-PRP GMT (Geometric Mean Titer) 1 Month After the Third Dose. | 11 months (1 month after the third dose) | Geometric Mean Titer (GMT) - This is an Antibody titer that is measured using a laboratory test to detect the presence and amount of antibodies in a person's blood. Anti-PRP (Antibodies against polyribosylribitol phosphate) titers were measured from blood samples taken at Month 11 (1 month after the third dose) |
Participant flow
Recruitment details
06-Dec-2006 (First Participant Enrolled in Study) to 03-Jun-2008 (Last Participant had their Last Visit). This study was conducted at 27 sites: 17 in Canada (16 of which were active sites) and 10 in Finland.
Pre-assignment details
Participants excluded for history of or prior vaccination for hepatitis B (Hep B) or Haemophilus influenzae Type B (Hib) disease and for administration of blood products. Participants also excluded if mother received Hep B, Hib vaccine, or blood products 6 months prior to participant birth.
Participants by arm
| Arm | Count |
|---|---|
| Modified Process Vaccine Modified Process Vaccine (0, 2, and 10 months), 5/7.5 µg (micrograms)
1 participant randomized but not vaccinated in the Modified Process Vaccine group; overall N is 269, not 270. | 269 |
| COMVAX™ COMVAX™ (0, 2, and 10 months), 5/7.5 µg (micrograms)
3 participants in the COMVAX™ group vaccinated but not randomized; overall N is 276, not 273 - due to issues randomizing via IVRS, in violation, all 3 participants were vaccinated as randomly assigned by the Investigator. | 276 |
| Total | 545 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Protocol Violation | 10 | 9 |
| Overall Study | Subject Randomized but Not Vaccinated | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 0 |
Baseline characteristics
| Characteristic | Modified Process Vaccine | COMVAX™ | Total |
|---|---|---|---|
| Age, Continuous | 67.7 Days | 68.3 Days | 68.0 Days |
| Sex: Female, Male Female | 129 Participants | 142 Participants | 271 Participants |
| Sex: Female, Male Male | 140 Participants | 134 Participants | 274 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 259 / — | 264 / — |
| serious Total, serious adverse events | 0 / — | 3 / — |
Outcome results
Primary
The Anti-HBs GMT (Geometric Mean Titer) 1 Month After the Third Dose.
Geometric Mean Titer (GMT) - This is an Antibody titer that is measured using a laboratory test to detect the presence and amount of antibodies in a person's blood. Anti-HBs (Antibodies against hepatitis B surface antigen) and Geometric Mean Titers were measured from blood samples taken at Month 11 (1 month after the third dose).
Time frame: 11 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 (GEOMETRIC_MEAN) |
|---|---|---|
| Modified Process Vaccine | The Anti-HBs GMT (Geometric Mean Titer) 1 Month After the Third Dose. | 4204.4 mIU/mL |
| COMVAX™ | The Anti-HBs GMT (Geometric Mean Titer) 1 Month After the Third Dose. | 1683.4 mIU/mL |
95% CI: [1.9, 3.3]
Primary
The Number of Anti-HBs Seroprotected Participants 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 Month 11 (1 month after the third dose)
Time frame: 11 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 Vaccine | The Number of Anti-HBs Seroprotected Participants 1 Month After the Third Dose. | 230 Participants |
| COMVAX™ | The Number of Anti-HBs Seroprotected Participants 1 Month After the Third Dose. | 226 Participants |
Comparison: The purpose of the primary analysis is to demonstrate that there is an adequate seroprotection rate (percentage of participants with anti-HBs \>=10mIU/mL) in each group at 1 month after the third dose. An adequate response requires the lower bound of the two-sided 95% confidence interval for the seroprotection rate to exceed 90%.95% CI: [98.7, 100]
Comparison: The purpose of the primary analysis is to demonstrate that there is an adequate seroprotection rate (percentage of participants with anti-HBs \>=10mIU/mL) in each group at 1 month after the third dose. An adequate response requires the lower bound of the two-sided 95% confidence interval for the seroprotection rate to exceed 90%.95% CI: [69.9, 99.9]
Secondary
The Anti-PRP GMT (Geometric Mean Titer) 1 Month After the Third Dose.
Geometric Mean Titer (GMT) - This is an Antibody titer that is measured using a laboratory test to detect the presence and amount of antibodies in a person's blood. Anti-PRP (Antibodies against polyribosylribitol phosphate) titers were measured from blood samples taken at Month 11 (1 month after the third dose)
Time frame: 11 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 (GEOMETRIC_MEAN) |
|---|---|---|
| Modified Process Vaccine | The Anti-PRP GMT (Geometric Mean Titer) 1 Month After the Third Dose. | 7.1 µg /mL |
| COMVAX™ | The Anti-PRP GMT (Geometric Mean Titer) 1 Month After the Third Dose. | 8.0 µg /mL |
Secondary
The Number of Anti-PRP Seroprotected Participants 1 Month After the Third Dose.
The number of participants as measured by the seroprotection rate (anti-polyribosylribitol phosphate antibodies greater than 1 µg/mL). Anti-PRP (Antibodies against polyribosylribitol phosphate) titers were measured from blood samples taken at Month 11 (1 month after the third dose)
Time frame: 11 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 Vaccine | The Number of Anti-PRP Seroprotected Participants 1 Month After the Third Dose. | 216 Participants |
| COMVAX™ | The Number of Anti-PRP Seroprotected Participants 1 Month After the Third Dose. | 210 Participants |
95% CI: [90, 96.6]
Comparison: No hypothesis is being tested. The purpose of the secondary analysis is to estimate the seroprotection rate (percentage of participants with anti-PRP \> 1µg/mL) in each group at 1 month after the third dose.95% CI: [87.8, 95.3]
Secondary
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: 0-11 months (recorded from first dose until the participant completes or discontinues)
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 Vaccine | The Total Number of Participants With Serious Vaccine-Related Clinical Adverse Experiences | 0 Participants |
| COMVAX™ | The Total Number of Participants With Serious Vaccine-Related Clinical Adverse Experiences | 0 Participants |