Meningitis, Meningococcemia
Conditions
Keywords
Meningitis, Meningococcemia, Neisseria meningitidis
Brief summary
The study investigated safety profile and the antibody responses to an experimental tetravalent meningococcal diphtheria conjugate vaccine (Menactra®) in children who have received a monovalent meningococcal C conjugate vaccine at least one year previously. Primary objective: To describe and compare the Serum Bactericidal Assay (SBA) antibody response for serogroup C in participants receiving Menactra® to the serogroup C antibody response in a control group of participants receiving a licensed Haemophilus Influenzae Type b (Hib) conjugate vaccine 28 days following vaccination.
Interventions
0.5 mL, Intramuscular
0.5 mL, Intramuscular
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 4 Years
Healthy volunteers
Yes
Inclusion criteria
: * Participant is healthy, as determined by medical history and physical examination. * Participant is 2 years to \< 5 years of age at the time of vaccination. * At least one year from primary vaccination with a monovalent meningococcal C conjugate vaccine has elapsed. * Parent/Guardian has signed an Ethics Committee-approved informed consent form. A culturally appropriate translation will be used for non-English speaking participants where required.
Exclusion criteria
: * Serious chronic disease (i.e. cardiac, renal, neurologic, metabolic, rheumatologic, etc.) * Known or suspected impairment of immunologic function * Acute medical illness with or without fever within the last 72 hours or an axillary temperature ≥ 37.5ºC at the time of inclusion * History of documented invasive meningococcal disease * Administration of immune globulin, other blood products within the last three months, injected or oral corticosteroids or other immunomodulatory therapy within six weeks of the study vaccine. Individuals on a tapering dose schedule of oral steroids lasting \< 7 days may be included in the trial as long as they have not received more than one course within the last two weeks prior to enrolment * Antibiotic therapy within the 72 hours prior to vaccination or 72 hours prior to drawing any blood sample * Received any vaccine in the 28-day period prior to enrolment, or scheduled to receive any vaccine during enrolment in the trial * Received a meningococcal C conjugate vaccine within one year prior to enrolment * Suspected or known hypersensitivity to any of the vaccine components * Unavailable for the entire study period or unable to attend the scheduled visits or to comply with the study procedures * Enrolled in another clinical trial * Any condition, which, in the opinion of the investigator, would pose a health risk to the participant or interfere with the evaluation of the vaccine.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Geometric Mean of Antibody Titers (GMTs) as Measured by Serum Bactericidal Assay (SBA) at Baseline (Day 0) and Day 28 Post-vaccination. | Day 0 (before) and 28 days post-vaccination |
Secondary
| Measure | Time frame |
|---|---|
| Participants With a ≥ 4-Fold Rise in Antibody Titers as Measured by Serum Bactericidal Assay (SBA) From Baseline to Day 28 Post-vaccination. | 28 days post-vaccination |
Countries
United Kingdom
Participant flow
Recruitment details
Subjects were recruited from August 2003 through March 2004 at 2 clinics in the United Kingdom.
Pre-assignment details
A total of 103 subjects that met the inclusion but none of the exclusion criteria were enrolled, 102 subjects were vaccinated.
Participants by arm
| Arm | Count |
|---|---|
| Menactra® Vaccine Group Participants received Menactra® Vaccine | 52 |
| Hiberix® Vaccine Group Participants received Hiberix® Vaccine | 51 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Not vaccinated | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Hiberix® Vaccine Group | Menactra® Vaccine Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 51 Participants | 52 Participants | 103 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 37.6 Months STANDARD_DEVIATION 8.3 | 37.0 Months STANDARD_DEVIATION 8.5 | 37.3 Months STANDARD_DEVIATION 8.3 |
| Region of Enrollment United Kingdom | 51 participants | 52 participants | 103 participants |
| Sex: Female, Male Female | 22 Participants | 28 Participants | 50 Participants |
| Sex: Female, Male Male | 29 Participants | 24 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 52 | 22 / 50 |
| serious Total, serious adverse events | 1 / 52 | 0 / 50 |
Outcome results
Primary
Geometric Mean of Antibody Titers (GMTs) as Measured by Serum Bactericidal Assay (SBA) at Baseline (Day 0) and Day 28 Post-vaccination.
Time frame: Day 0 (before) and 28 days post-vaccination
Population: SBA geometric mean titers for each of the 4 meningococcal serogroups was evaluated in the per-protocol population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Menactra® Vaccine Group | Geometric Mean of Antibody Titers (GMTs) as Measured by Serum Bactericidal Assay (SBA) at Baseline (Day 0) and Day 28 Post-vaccination. | Meningococcal Serogroup C - Day 28 | 12534.67 Titers |
| Menactra® Vaccine Group | Geometric Mean of Antibody Titers (GMTs) as Measured by Serum Bactericidal Assay (SBA) at Baseline (Day 0) and Day 28 Post-vaccination. | Meningococcal Serogroup A - Day 28 | 11404.16 Titers |
| Menactra® Vaccine Group | Geometric Mean of Antibody Titers (GMTs) as Measured by Serum Bactericidal Assay (SBA) at Baseline (Day 0) and Day 28 Post-vaccination. | Meningococcal Serogroup Y - Day 0 | 236.61 Titers |
| Menactra® Vaccine Group | Geometric Mean of Antibody Titers (GMTs) as Measured by Serum Bactericidal Assay (SBA) at Baseline (Day 0) and Day 28 Post-vaccination. | Meningococcal Serogroup A - Day 0 | 136.33 Titers |
| Menactra® Vaccine Group | Geometric Mean of Antibody Titers (GMTs) as Measured by Serum Bactericidal Assay (SBA) at Baseline (Day 0) and Day 28 Post-vaccination. | Meningococcal Serogroup Y - Day 28 | 4031.98 Titers |
| Menactra® Vaccine Group | Geometric Mean of Antibody Titers (GMTs) as Measured by Serum Bactericidal Assay (SBA) at Baseline (Day 0) and Day 28 Post-vaccination. | Meningococcal Serogroup C - Day 0 | 76.11 Titers |
| Menactra® Vaccine Group | Geometric Mean of Antibody Titers (GMTs) as Measured by Serum Bactericidal Assay (SBA) at Baseline (Day 0) and Day 28 Post-vaccination. | Meningococcal Serogroup W-135 - Day 0 | 26.07 Titers |
| Menactra® Vaccine Group | Geometric Mean of Antibody Titers (GMTs) as Measured by Serum Bactericidal Assay (SBA) at Baseline (Day 0) and Day 28 Post-vaccination. | Meningococcal Serogroup W-135 - Day 28 | 5978.03 Titers |
| Hiberix® Vaccine Group | Geometric Mean of Antibody Titers (GMTs) as Measured by Serum Bactericidal Assay (SBA) at Baseline (Day 0) and Day 28 Post-vaccination. | Meningococcal Serogroup W-135 - Day 28 | 32 Titers |
| Hiberix® Vaccine Group | Geometric Mean of Antibody Titers (GMTs) as Measured by Serum Bactericidal Assay (SBA) at Baseline (Day 0) and Day 28 Post-vaccination. | Meningococcal Serogroup A - Day 0 | 99.66 Titers |
| Hiberix® Vaccine Group | Geometric Mean of Antibody Titers (GMTs) as Measured by Serum Bactericidal Assay (SBA) at Baseline (Day 0) and Day 28 Post-vaccination. | Meningococcal Serogroup A - Day 28 | 199.31 Titers |
| Hiberix® Vaccine Group | Geometric Mean of Antibody Titers (GMTs) as Measured by Serum Bactericidal Assay (SBA) at Baseline (Day 0) and Day 28 Post-vaccination. | Meningococcal Serogroup C - Day 0 | 26.91 Titers |
| Hiberix® Vaccine Group | Geometric Mean of Antibody Titers (GMTs) as Measured by Serum Bactericidal Assay (SBA) at Baseline (Day 0) and Day 28 Post-vaccination. | Meningococcal Serogroup C - Day 28 | 22.63 Titers |
| Hiberix® Vaccine Group | Geometric Mean of Antibody Titers (GMTs) as Measured by Serum Bactericidal Assay (SBA) at Baseline (Day 0) and Day 28 Post-vaccination. | Meningococcal Serogroup Y - Day 0 | 266.05 Titers |
| Hiberix® Vaccine Group | Geometric Mean of Antibody Titers (GMTs) as Measured by Serum Bactericidal Assay (SBA) at Baseline (Day 0) and Day 28 Post-vaccination. | Meningococcal Serogroup Y - Day 28 | 298.63 Titers |
| Hiberix® Vaccine Group | Geometric Mean of Antibody Titers (GMTs) as Measured by Serum Bactericidal Assay (SBA) at Baseline (Day 0) and Day 28 Post-vaccination. | Meningococcal Serogroup W-135 - Day 0 | 24.44 Titers |
Secondary
Participants With a ≥ 4-Fold Rise in Antibody Titers as Measured by Serum Bactericidal Assay (SBA) From Baseline to Day 28 Post-vaccination.
Time frame: 28 days post-vaccination
Population: SBA titers for each of the 4 meningococcal serogroups was evaluated in the per-protocol population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Menactra® Vaccine Group | Participants With a ≥ 4-Fold Rise in Antibody Titers as Measured by Serum Bactericidal Assay (SBA) From Baseline to Day 28 Post-vaccination. | Meningococcal Serogroup A | 43 Participants |
| Menactra® Vaccine Group | Participants With a ≥ 4-Fold Rise in Antibody Titers as Measured by Serum Bactericidal Assay (SBA) From Baseline to Day 28 Post-vaccination. | Meningococcal Serogroup C | 41 Participants |
| Menactra® Vaccine Group | Participants With a ≥ 4-Fold Rise in Antibody Titers as Measured by Serum Bactericidal Assay (SBA) From Baseline to Day 28 Post-vaccination. | Meningococcal Serogroup W-135 | 43 Participants |
| Menactra® Vaccine Group | Participants With a ≥ 4-Fold Rise in Antibody Titers as Measured by Serum Bactericidal Assay (SBA) From Baseline to Day 28 Post-vaccination. | Meningococcal Serogroup Y | 35 Participants |
| Hiberix® Vaccine Group | Participants With a ≥ 4-Fold Rise in Antibody Titers as Measured by Serum Bactericidal Assay (SBA) From Baseline to Day 28 Post-vaccination. | Meningococcal Serogroup W-135 | 8 Participants |
| Hiberix® Vaccine Group | Participants With a ≥ 4-Fold Rise in Antibody Titers as Measured by Serum Bactericidal Assay (SBA) From Baseline to Day 28 Post-vaccination. | Meningococcal Serogroup A | 11 Participants |
| Hiberix® Vaccine Group | Participants With a ≥ 4-Fold Rise in Antibody Titers as Measured by Serum Bactericidal Assay (SBA) From Baseline to Day 28 Post-vaccination. | Meningococcal Serogroup C | 2 Participants |
| Hiberix® Vaccine Group | Participants With a ≥ 4-Fold Rise in Antibody Titers as Measured by Serum Bactericidal Assay (SBA) From Baseline to Day 28 Post-vaccination. | Meningococcal Serogroup Y | 1 Participants |