Invasive meningococcal disease is an uncommon but serious disease predominantly affecting children. This phase 2b study evaluated MenABCWY in 6-month-old infants followed by MenB-fHbp and MenABCWY in 2-month-old infants, the latter being the target age and intervention. Participants were randomized to MenABCWY, 60 µg or 120 µg MenB-fHbp+MenACWY-TT, or 4CMenB+MenACWY-TT, administered as 2 primary and 1 booster dose. The primary safety objective was to describe the safety profile of MenABCWY in participants enrolled at 2 months. Primary immunogenicity objectives were the percentage of participants achieving seroprotective serum bactericidal antibody using human complement titers. Overall, 314 and 12 participants were randomized to sentinel cohort and open-label expanded-enrollment stages, respectively. Based on 2 reports of fever requiring invasive investigations and accompanied by cerebrospinal fluid pleocytosis and 1 report arising from a previous study, the Sponsor terminated the study. Local reactions and systemic events after primary vaccination were generally mild to moderate, and tended to be higher with MenABCWY versus 4CMenB+MenACWY-TT. Immunogenicity data suggest that 1 month after vaccination 2, MenABCWY responses for MenA/C/W/Y were robust and comparable with 4CMenB+MenACWY-TT in 2-month-old participants. Immune responses for MenB test strains were higher with MenABCWY versus 4CMenB+MenACWY-TT and generally similar with 60 µg and 120 µg MenB-fHbp+MenACWY-TT or MenABCWY. Based on the limited results, the consistency of MenB immune responses with 60 µg and 120 µg MenB-fHbp suggests doses < 60 µg could be investigated to assess whether a more acceptable safety profile in conjunction with beneficial immune responses is possible in 2-month-old infants.