MenACYW-TT Coadministration Trial Reports Non-Inferior Immune Responses
Key Takeaways
- Both co-primary non-inferiority endpoints were met at the prespecified 6-month and 12- to 15-month assessments.
- Routine pediatric vaccine responses were also non-inferior with MenACYW-TT coadministration.
- Reactogenicity and broader safety findings were comparable overall, with no new safety concerns identified.
The partially modified double-blind, randomized, parallel-group, active-controlled study was conducted at 69 sites in the USA and Puerto Rico. Healthy infants were 42 to 89 days old at enrollment, and baseline demographic characteristics were balanced between groups. Participants received a four-dose 3 + 1 series of MenACYW-TT or licensed MenACWY-CRM concomitantly with routine pediatric vaccines including DTaP5-IPV/Hib, PCV13, rotavirus, hepatitis B, MMR, varicella, and, in some second-year groups, hepatitis A. The study ran from April 2018 to September 2023; enrollment and randomization occurred from April 2018 to November 2021, and follow-up continued for 6 months after the final vaccination. The co-primary immunogenicity assessments were prespecified for 30 days after dose three at 6 months and 30 days after dose four at 12 to 15 months.
Across serogroups A, C, W, and Y, non-inferiority was shown for hSBA titers of at least 1:8 after the third dose and for seroresponse after the fourth dose. Thirty days after dose three at 6 months, rates were 77.9% to 99.0% with MenACYW-TT and 67.7% to 92.9% with MenACWY-CRM. Thirty days after dose four at 12 to 15 months, seroresponse rates were 79.4% to 97.6% and 77.6% to 96.4%, respectively. After four doses, hSBA geometric mean titers were comparable for serogroup A and descriptively higher for serogroups C, W, and Y. The prespecified non-inferiority criteria were met.
Immune responses to concomitantly administered routine pediatric vaccines were also non-inferior with MenACYW-TT coadministration in the registered study. Assessments covered infant-series responses after the 6-month visit and follow-up analyses after vaccinations in the second year of life. It also described bactericidal-antibody persistence before dose four and comparable MenACYW-TT seroresponse findings whether the fourth dose was given at 12 to 15 months or 15 to 18 months, although hSBA geometric mean titers for serogroups Y and W were higher with the later schedule. Investigators did not identify evidence of immune interference in the reported immunogenicity analyses.
Solicited injection-site and systemic reactions were mostly mild to moderate and usually resolved within 1 to 3 days. During the study, at least one serious adverse event occurred in 99 of 1,727 MenACYW-TT recipients and 38 of 867 MenACWY-CRM recipients. At least one adverse event of special interest occurred in 13 of 1,727 and 5 of 867 participants, and immediate unsolicited events within 30 minutes occurred once in each group. One death was reported and was not considered related to vaccination, and post-vaccination fever in the comparator group was the one serious adverse event assessed as related by both investigator and sponsor; a febrile convulsion in the MenACYW-TT group was assessed as related by the investigator but not by the sponsor. The findings were based on immunogenicity surrogate endpoints rather than direct measurements of disease prevention.