Table 2. Randomized controlled phase 2–3 studies performed with 4CMenB prior to license.
| Study description | 4CMenB | Total subjects | Results | Reference |
|---|---|---|---|---|
| Phase 2b/3 | 1,2 or 3 doses of 4CMenB interval 1,2 or 6 mo | 1631 healthy persons, aged 11–17 y | Vaccine was safe. Vaccination with 2 doses with an interval of 6 mo, and not 1 or 2 mo, provided good SBA titers. A 3rd dose provided no additional benefit |
39 |
| Phase 2b | 3 doses 4CMenB at 2,4,6 mo concomitantly with routine infant vaccination 3 doses 4CMenB at 2,4,6 mo and at 3,5,7 mo routine infant vaccination (intercalated scheme) 3 doses concomitantly at 2,3,4 mo simultaneously routine infant vaccination Only routine infant vaccination at 2,3,4 mo |
1885 infants | After each vaccination, fever (≥38 °C) was reported; 76–80% in the groups receiving 4CMenB and the routine vaccines simultaneously, 71% in the intercalated group, and in 51% in the group receiving the routine vaccines only. No influence of clinical significance was observed of 4CMenB vaccination on the immune response to routine vaccination. Higher SBA titers were observed in intercalated vaccination group. In all groups: A SBA titer of ≥1:5 was observed in 99% or more of infants against strains 44/76-SL (fHbp) and 5/99 (NadA), and in 79–86% against the NZ98/254 strain (OMV) |
38 |
| Phase 3 | Safety: Routine vaccines* alone or concomitantly with 3 doses of 4CMenB or MenC at 2,4,6 mo Immunogenicity: Routine vaccines* alone or concomitantly with 3 doses of 4CMenB Fourth (booster) dose at 12 mo with or without MMRV vaccination |
1003 infants 2627 infants 1555 infants |
Concomitantly 4CMenB was associated with increased fever (≥38.5 °C) rates. In total 77% (1912 of 2478) of infants had fever after any 4CMenB dose, compared with 45% (295 of 659) after routine vaccines alone, and 47% (228 of 490) with MenC No clear influence of 4CMenB vaccination was observed on the immune response to routine vaccination. A SBA titer of ≥1:5 was observed in 100% of infants against strains 44/76-SL (fHbp) and 5/99 (NadA), and in 84% against the NZ98/254 strain (OMV). In a subset (n = 100), 84% had SBA titer ≥1:5 for NHBA. 95–100% of boost-vaccinated infants had SBA titers ≥1:5 for all antigens with or without concomitant MMRV |
37 |
*Routine vaccination: with 7-valent pneumococcal and combined diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B, Hemophilus influenzae type b DTaP-IPV-HepB-Hib vaccine. MenC, serogroup C conjugate vaccine; MMRV, measles-mumps-rubella-varicella vaccine.