Table 2.
Clinical studies of MenACWY-TT in infants, toddlers, and adolescents
| Study | Clinical trial registration number | Study, n | Location | Design | Immunogenicity | Safety |
|---|---|---|---|---|---|---|
| Infants | ||||||
| Merino Arribas et al., 2017 [94] | ClinicalTrials.gov: NCT01144663 | 2095 | Spain, Germany, Estonia |
Randomization 1:1:1:1 • MenACWY-TT at 2, 3, 4, and 12 months • MenACWY-TT at 2, 4, and 12 months • MenC-CRM197 at 2, 4, and 12 months • MenC-TT at 2, 4, and 12 months |
MenACWY-TT (two or three doses) was noninferior to two doses of either MenC vaccine. After the primary series, ≥ 88.5% and ≥ 93.1% of subjects had titers ≥ 1:8 in hSBA and rSBA, respectively, for each meningococcal serogroup. After the booster dose, ≥ 99.1% had hSBA or rSBA titers ≥ 1:8 | No increase in reactogenicity was observed in infants who received three doses of MenACWY-TT. One SAE (epilepsy) was considered potentially related to vaccination |
| Dbaibo et al., 2018 [95] | ClinicalTrials.gov: NCT01340898 | 750 | Lebanon, Mexico |
Randomization 2:1:1 • MenACWY-TT at 2, 4, 6, and 15–18 months • MenACWY-TT at 6 and 15–18 months • MenACWY-TT at 15–18 months |
After the three-dose primary series, ≥ 99.4% of subjects had rSBA titers ≥ 1:8 for each meningococcal serogroup; this rose to ≥ 99.6% after the booster. After one dose + booster, ≥ 99.3% of subjects had rSBA titers ≥ 1:8. After one dose at 15–18 months, ≥ 96.3% of subjects had rSBA titers ≥ 1:8 | Safety and tolerability were comparable across dosing schedules |
| Toddlers | ||||||
| Vesikari et al., 2011 [96] | ClinicalTrials.gov: NCT00474266 | 1000 | Finland |
Randomization 3:3:1:1 of toddlers aged 12–23 months • MenACWY-TT + MMRV/MMRV 84 days later • MenACWY-TT/MMRV at 42 and 84 days later • MMRV/MenC 42 days later/MMRV 84 days after dose 1 • MenC/MMRV at 42 and 84 days later |
MenACWY-TT was noninferior to MenC. 42 days after MenACWY-TT vaccination, ≥ 99.7% of subjects had rSBA titers ≥ 1:8 against each meningococcal serogroup. All subjects in the MenACWY-TT + MMRV group seroconverted against measles and rubella, 87.7% seroconverted against mumps, and 97.9% seroconverted against varicella. Coadministration was noninferior to administering vaccines separately | All groups had comparable safety profiles with the exception of fever and rash, which were higher in both groups that received MMRV at Day 0. (Safety and reactogenicity were assessed for 43 days following the first vaccination; SAEs were reported for 6 months) |
| Cutland et al., 2018 [97] | ClinicalTrials.gov: NCT01939158 | 802 | Australia, Canada, Czech Republic, Panama, South Africa, Turkey |
Randomization 1:1:1:1 of toddlers aged 12–14 months • One dose of MenACWY-TT • Two doses of MenACWY-TT at 2 months apart • One dose of MenACWY-TT coadministered with PCV13 • One dose of PCV13 followed by 1 dose of MenACWY-TT administered 2 mo later |
≥ 92.8% of subjects had rSBA titers ≥ 1:8 for each meningococcal serogroup. GMTs increased markedly compared with prevaccination levels. Dose 2 elicited comparable immune responses to dose 1. Coadministration with PCV13 did not affect immunogenicity | Redness was the most common local reaction after dose 1 of MenACWY-TT. Safety was comparable after dose 2. Coadministration with PCV13 did not affect the safety profile of either vaccine |
| Children | ||||||
| Vesikari et al., 2012 [98] | ClinicalTrials.gov: NCT00427908 | 309 | Finland |
Randomization 3:1 of children aged 2–10 years • MenACWY-TT (1 dose) • Men-PS (1 dose) |
At 1 month postvaccination, MenACWY-TT was noninferior to Men-PS. Response rates measured by rSBA were ≥ 94.3% in the MenACWY-TT group and ≥ 81.2% in the Men-PS group. All subjects in both groups had rSBA titers ≥ 1:8 against each meningococcal serogroup | Pain was the most frequent solicited local symptom and was more frequently reported in the Men-PS groups. Redness and swelling were more common in the MenACWY-TT groups |
| Vesikari et al., 2016 [99] | ClinicalTrials.gov: NCT00427908 |
Y 4: 217 Y 5: 111 |
Finland |
Long-term follow-up phase of the vaccination study described above • Evaluated antibody persistence up to 5 years after MenACWY-TT or Men-PS |
rSBA antibody persistence (% subjects ≥ 1:8) at year 4 was 50.0–90.4% in the MenACWY-TT group and 6.9–41.4% in the Men-PS group At year 5, antibody persistence against serogroups A, W, and Y was 78.6–90.8% in the MenACWY-TT group and 0.0–15.4% in the Men-PS group. (At year 5, MenC titers were artificially elevated due to withdrawal of subjects with MenC rSBA < 1:8 after the year 4 visit) |
No SAEs related to vaccination were reported from 6 months following primary vaccination through to the year 5 visit |
| Adolescents | ||||||
| Ishola et al., 2015 [100] | ClinicalTrials.gov: NCT01192997 | 93 | United Kingdom |
Subjects previously vaccinated with MenC at 3.5–5.9 years of age were randomized 1:1 at 16–19 years of age • MenACWY-TT booster • MenACWY-CRM197 booster |
Among subjects boosted with MenACWY-TT vs. MenACWY-CRM, proportions of subjects with rSBA titers ≥ 1:8 were 100% vs 98–100% at 1 month postvaccination, 95–100% vs 91–100% at 6 months postvaccination, and 96–100% vs. 100% at 9 months postvaccination | Local or general reactions were generally similar between groups. Severe redness and muscle pain were more common with MenACWY-CRM197; severe tiredness was more common with MenACWY-TT |
| van Ravenhorst et al., 2017 [101, 102] | EudraCT: 2013-001823-38 | 501 | Netherlands |
Subjects previously vaccinated with MenC-TT at 14 months–3 years were randomized 1:1 at 10, 12, or 15 years of age • MenACWY-TT booster • MenC-TT booster |
≥ 94.5% of subjects vaccinated with MenACWY-TT achieved rSBA titers ≥ 1:8 for each serogroup at 1 month postbooster. At 1 year postbooster, 95.1% of evaluated subjects maintained rSBA titers ≥ 1:8 against all of serogroups A, W, and Y, and ≥ 97.3% had rSBA titers ≥ 1:8 for serogroup C | N/A |
| Halperin et al., 2014 [103] | ClinicalTrials.gov: NCT01165242 | 1011 | United States, Canada |
Subjects aged 11–25 years randomized 1:1:1 to receive 1 vaccine dose • MenACWY-TT (lot A) • MenACWY-TT (lot B) • MenACWY-D |
MenACWY-TT (lot A) was noninferior to MenACWY-D at 1 month postvaccination. Vaccine response rates against each serogroup measured by hSBA were 51.0–82.5% in the MenACWY-TT groups and 39.0–76.3% in the MenACWY-D group (Vaccine response defined as hSBA titer ≥ 1:8 in initially seronegative subjects and fourfold titer increase in initially seropositive subjects) |
Rates of local and systemic AEs and grade 3 AEs were similar among the 3 vaccine groups |
| Borja-Tabora et al., 2015 [104] | ClinicalTrials.gov: NCT00356369 | 404 | Philippines, Saudi Arabia |
Evaluated bactericidal antibody persistence up to 5 years after vaccination • In the primary phase of the study, 500 subjects aged 11–55 years were randomized 3:1 to receive 1 dose of MenACWY-TT or Men-PS • 284 of the 404 subjects evaluated at year 5 were aged 11–17 years at time of vaccination |
At year 5, proportions of adolescent subjects with rSBA antibody titers ≥ 1:8 for each serogroup ranged from 74.0–92.8% in the MenACWY-TT group and 23.7–80.3% in the Men-PS group | No SAEs related to vaccination were reported |
| Baxter et al., 2015 [105] | ClinicalTrials.gov: NCT00715910 | 189 | United States |
Evaluated antibody persistence up to 5 years after MenACWY-TT (n = 144 at year 5) or MenACWY-D (n = 45 at year 5) • In the primary phase of the study, subjects aged 10–25 years were randomized 3:1 to receive 1 dose of MenACWY-TT or MenACWY-D |
At 5-year postvaccination, percentages of subjects with hSBA titers ≥ 1:8 against serogroups A, C, W, and Y were 48.9%, 92.9%, 87.0%, and 94.4%, respectively, in the MenACWY-TT group and 44.4%, 79.5%, 84.1%, and 90.9% in the MenACWY-D group | No related SAEs were reported during the 5-year persistence phase of the study |
| Rivera et al., 2018 [106] | ClinicalTrials.gov: NCT01767376 | 691 | Korea, Germany, Dominican Republic |
Randomization 1:1:1 of individuals aged 11–25 years • MenACWY-TT + Tdap MenACWY-TT/Tdap 1 month later • Tdap/MenACWY-TT 1 month later |
Coadministration was noninferior for MenACWY-TT, and all Tdap antigens except pertussis. 96.9–100% of subjects had anti-meningococcal rSBA titers or anti-Tdap antibody concentrations meeting or exceeding assay cutoffs for all serogroups | Coadministration did not increase frequencies of local reactions, systemic events, or unsolicited AEs |
| Rivera et al., 2018 [107] | ClinicalTrials.gov: NCT01755689 | 1300 | Estonia, Thailand, Dominican Republic |
Randomization 1:1:1:1:1 of female subjects aged 9–25 years • MenACWY-TT at month 0/HPV2 at month 1, 2, and 7 • MenACWY-TT + HPV2 at month 0/HPV2 at month 1 and 6 HPV2 at month 0, 1, and 6 • MenACWY-TT + HPV2 + Tdap at month 0/HPV2 at month 1 and 6 • HPV2 + Tdap at month 0/HPV2 at month 1 and 6 |
Concomitant vaccination of MenACWY-TT and HPV2 was noninferior to individual administration of either vaccine. ≥ 97.3% of subjects had rSBA titers ≥ 1:8 against each of the meningococcal serogroups, and ≥ 99.6% of subjects in each group had anti-HPV antibodies meeting or exceeding prespecified thresholds. Compared with Tdap + HPV2, coadministration of all three vaccines met noninferiority criteria for diphtheria and tetanus but not pertussis antigens; however, ≥ 98.0% of subjects in each group had pertussis antigen antibodies above the assay cutoff | Concomitant administration did not affect safety and tolerability of any vaccine |
AE adverse event, CRM cross-reactive material, GMT geometric mean titer, HPV2 2-valent human papillomavirus vaccine, hSBA serum bactericidal assay using human complement, MenACWY meningococcal serogroups A, C, W, and Y, MenC meningococcal serogroup C, MMRV measles, mumps, rubella and varicella, NA not available, PCV13 13-valent pneumococcal conjugate vaccine, PS polysaccharide, rSBA serum bactericidal assay using rabbit complement, SAE serious adverse event, Tdap tetanus, diphtheria, and acellular pertussis vaccine, TT tetanus toxoid