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MenHibrix

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MenHibrix

CLINICAL PHARMACOLOGY

Mechanism of Action

Neisseria meningitides

The presence of bactericidal anti-capsular meningococcal antibodies has been associated with protection from invasive meningococcal disease.8 MENHIBRIX induces production of bactericidal antibodies specific to the capsular polysaccharides of serogroups C and Y.

Haemophilus influenzae type b

Specific levels of antibodies to PRP (anti-PRP) have been shown to correlate with protection against invasive disease due to H. influenzae type b. Based on data from passive antibody studies9 and a clinical efficacy study with unconjugated Haemophilus b polysaccharide vaccine10, an anti-PRP concentration of 0.15 mcg/mL has been accepted as a minimal protective level. Data from an efficacy study with unconjugated Haemophilus b polysaccharide vaccine indicate that an anti-PRP concentration of ≥ 1.0 mcg/mL predicts protection through at least a 1-year period.11,12 These antibody levels have been used to evaluate the effectiveness of H. influenzae type b-containing vaccines, including MENHIBRIX.

Clinical Studies

Immunological Evaluation

In Study 009/0105 the immune response to MENHIBRIX and control vaccines was evaluated in a subset of US participants. In this clinical study, MENHIBRIX and Hib control vaccines were administered concomitantly with routinely recommended US-licensed vaccines [see ADVERSE REACTIONS]. Among participants in the ATP immunogenicity cohort for both vaccine groups combined, 47% were female; 81% of participants were white, 8% were black, 4% were Hispanic, 1% were Asian, and 6% were of other racial/ethnic groups.

Study objectives included evaluation of N. meningitidis serogroups C (MenC) and Y (MenY) as measured by serum bactericidal assay using human complement (hSBA) and antibodies to PRP as measured by enzyme-linked immunosorbent assay (ELISA) in sera obtained approximately one month (range 21 to 48 days) after dose 3 of MENHIBRIX or PRP-T and approximately 6 weeks (range 35 to 56 days) after dose 4 of MENHIBRIX or PRP-OMP. The hSBA-MenC and hSBA-MenY geometric mean antibody titers (GMTs) and the percentage of participants with hSBA-MenC and hSBA-MenY levels ≥ 1:8 are presented in Table 2. Anti-PRP geometric mean antibody concentrations (GMCs) and the percentage of participants with anti-PRP levels ≥ 0.15 mcg/mL and ≥ 1.0 mcg/mL are presented in Table 3.

Table 2: Bactericidal Antibody Responses Following MENHIBRIX (One Month After Dose 3 and 6 Weeks After Dose 4) in US Children Vaccinated at 2, 4, 6, and 12 to 15 Months of Age (ATP Cohort for Immunogenicity)

  MENHIBRIX
Post-Dose 3
MENHIBRIX
Post-Dose 4
hSBA-MenC N = 491 N = 331
% ≥ 1:8 98.8 98.5a
95% CI 97.4, 99.6 96.5, 99.5
GMT 968 2040
95% CI 864, 1084 1746, 2383
hSBA-MenY N = 481 N = 342
% ≥ 1:8 95.8 98.8a
95% CI 93.7, 97.4 97.0, 99.7
GMT 237 1390
95% CI 206, 272 1205, 1602
ATP = according to protocol; CI = confidence interval; GMT = geometric mean antibody titer.
N = number of US children eligible for inclusion in the ATP immunogenicity cohort for whom serological results were available for the post-dose 3 and post-dose 4 immunological evaluations.
a Acceptance criteria were met (lower limit of 95% CI for the percentage of participants with hSBA-MenC and hSBA-MenY titers ≥ 1:8 ≥ 90% following 4 doses).

Table 3: Comparison of anti-PRP Responses Following MENHIBRIX or Haemophilus b Conjugate Vaccinea (One Month After Dose 3 and 6 Weeks After Dose 4) in US Children Vaccinated at 2, 4, 6, and 12 to 15 Months of Age (ATP Cohort for Immunogenicity)

  Post-Dose 3 Post-Dose 4
MENHIBRIX PRP-T MENHIBRIX PRP-OMP
Anti-PRP N = 518 N = 171 N = 361 N = 126
% ≥ 0.15 mcg/mL 100 98.2 100 100
95% CI 99.3, 100 95.0, 99.6 99.0, 100 97.1, 100
% ≥ 1.0 mcg/mL 96.3b 91.2 99.2b 99.2
95% CI 94.3, 97.8 85.9, 95.0 97.6, 99.8 95.7, 100
GMC (mcg/mL) 11 6.5 34.9 20.2
95% CI 10.0, 12.1 5.3, 7.9 30.7, 39.6 16.4, 24.9
ATP = according to protocol; anti-PRP = antibody concentrations to H. influenzae capsular polysaccharide; CI = confidence interval; GMC = geometric mean antibody concentration.
N = number of US children eligible for inclusion in the ATP immunogenicity cohort for whom serological results were available for the post-dose 3 and post-dose 4 immunological evaluations.
a US-licensed monovalent Haemophilus b Conjugate Vaccine for doses 1, 2, and 3 (PRP-T) and for dose 4 (PRP-OMP).
b Non-inferiority was demonstrated (lower limit of 95% CI on the group difference of MENHIBRIX minus Haemophilus b Conjugate Vaccine ≥ -10%).

Concomitant Vaccine Administration

In participants who received MENHIBRIX concomitantly with PEDIARIX and PCV7 at 2, 4, and 6 months of age, there was no evidence for reduced antibody response to pertussis antigens (GMC to pertussis toxin, filamentous hemagglutinin, and pertactin), diphtheria toxoid (antibody levels ≥ 0.1 IU/mL), tetanus toxoid (antibody levels ≥ 0.1 IU/mL), poliovirus types 1, 2, and 3 (neutralizing antibody levels ≥ 1:8 to each virus), hepatitis B (anti-hepatitis B surface antigen ≥ 10 mIU/mL) or PCV7 (antibody levels ≥ 0.2 mcg/mL and GMC to each serotype) relative to the response in control participants administered PRP-T concomitantly with PEDIARIX and PCV7. The immune responses to PEDIARIX3,5 and PCV73 were evaluated one month following dose 3.

There was no evidence for interference in the immune response to MMR and varicella vaccines (initially seronegative participants with anti-measles ≥ 200 mIU/mL, anti-mumps ≥ 51 ED50, anti-rubella ≥ 10 IU/mL, and anti-varicella ≥ 1:40) administered at 12 to 15 months of age concomitantly with MENHIBRIX and PCV7 relative to these vaccines administered concomitantly with PRP-OMP and PCV7.4,5 The immune responses to MMR and varicella vaccines were evaluated 6 weeks post-vaccination. Data are insufficient to evaluate potential interference when a fourth PCV7 dose is administered concomitantly with MENHIBRIX at 12 to 15 months of age.

REFERENCES

All NCT numbers are as noted in the National Library of Medicine clinical trial database (see www.clinicaltrials.gov).

3. NCT00129129 (005/006).

4. NCT00134719 (007/008).

5. NCT00289783 (009/010).

8. Goldschneider I, Gotschlich EC, Artenstein MS. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med 1969;129:1307-1326.

9. Robbins JB, Parke JC, Schneerson R, et al. Quantitative measurement of “natural” and immunization-induced Haemophilus influenzae type b capsular polysaccharide antibodies. Pediatr Res 1973;7:103-110.

10. Peltola H, Käythy H, Sivonen A, et al. Haemophilus influenzae type b capsular polysaccharide vaccine in children: A double-blind field study of 100,000 vaccinees 3 months to 5 years of age in Finland. Pediatrics 1977;60:730-737.

11. Käythy H, Peltola H, Karanko V, et al. The protective level of serum antibodies to the capsular polysaccharide of Haemophilus influenzae type b. J Infect Dis 1983;147:1100.

12. Anderson P. The protective level of serum antibodies to the capsular polysaccharide of Haemophilus influenzae type b. J Infect Dis 1984;149:1034.

Last reviewed on RxList: 7/23/2012
This monograph has been modified to include the generic and brand name in many instances.

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