Trial Outcomes & Findings for Meningococcal Serogroup ACYWX Conjugate Vaccine in Comparison With MenACWY-TT Conjugate Vaccine (NCT NCT05093829)

Participants were recruited in Mali, enrollment began March 24, 2022, and all follow up at Day 29 was complete by March 10, 2023.

1331 participants were assessed for eligibility and 6 were ineligible and excluded. 1325 participants received step 1 randomization to Group 1 (meningococcal vaccination at 9 months of age, n=602) or Group 2 (meningococcal vaccination at 15 months of age, n=723). 1202 participants received step 2 randomization to meningococcal vaccine study arm, and 123 Group 2 participants were excluded due to lost to follow-up or ineligibility or Group 2 target (n=600) met.

Meningococcal Serogroup ACYWX Conjugate Vaccine in Comparison With MenACWY-TT Conjugate Vaccine

Null hypothesis: The immune response to meningitis serogroup "S" at Day 29 elicited by one dose of NmCV-5 is inferior to the immune response elicited by one dose of MenACWY-TT. Alternative hypothesis: The immune response to meningitis serogroup "S" at Day 29 elicited by one dose of NmCV-5 is non-inferior, by a pre-specified margin, to the immune response elicited by one dose of MenACWY-TT, where "S" denotes one of the meningitis serogroups: A, C, W or Y. Endpoints are the seroprotective response at Day 29 to serogroups A, C, W and Y in the NmCV-5 arm and seroprotective response at Day 29 to serogroups A, C, W and Y in the MenACWY-TT arm with seroprotective response defined as serogroup specific rSBA antibody titers ≥ 8. Non-inferiority comparisons are made between study vaccination arms within each study age group (9 months or 15 months of age). Proportions and difference in proportions are reported as percentages (number of infants per 100).

Null hypothesis: At Day 29, the immune response to meningitis serogroup X elicited by one dose of NmCV-5 is inferior to the lowest immune response (among meningitis serogroups A, C, W or Y) elicited by one dose of MenACWY-TT. Alternative hypothesis: At Day 29, the immune response to meningitis serogroup X elicited by one dose of NmCV-5 is non-inferior, by a pre-specified margin, to the lowest immune response (among meningitis serogroups A, C, W or Y) elicited by one dose of MenACWY-TT. Endpoints are the seroprotective response to serogroup X in the NmCV-5 arm and the minimum seroprotective response among serogroups A, C, W and Y in the MenACWY-TT arm at Day 29 with seroprotective response defined as serogroup specific rSBA antibody titers ≥ 8. Non-inferiority comparisons are made between study vaccination arms within each study age group (9 months or 15 months). Proportions and difference in proportions are reported as percentages (number of infants per 100).

To assess the safety and tolerability of a single dose of NmCV-5 or MenACWY-TT, when given concomitantly with routine vaccines, all Serious Adverse Events (SAE) occurring during the first 6 months of the follow-up period after meningococcal vaccination are reported. Endpoints are the number of participants with unsolicited adverse events that are reported as Serious Adverse Events (SAEs) according to ICH/GCP guidelines or the study protocol collected from the time of Step 2 randomization and vaccination and with date of event onset up to and including Study Day 181.

To assess the safety and tolerability of a single dose of NmCV-5 or MenACWY-TT, when given concomitantly with routine vaccines, all solicited AEs occurring during a 7-day follow-up period after meningococcal vaccination are reported. Solicited AEs include injection site (local) events (erythema/redness, induration/swelling, pain and/or tenderness) and systemic events (irritability, drowsiness/lethargy, decrease eating/anorexia, vomiting, fever (axillary), and feverish). Endpoints are the number of participants with solicited adverse events collected from about 30 minutes after meningococcal vaccination to Study Day 8 (7 days after vaccination). NOTE: Capture of data for symptom Feverish began on June 15, 2022, so some participants were not assessed for this symptom. Also, Fever (Axillary) is objectively measured by oral temperature and Feverish is a subjective observation from a parent who feels their infant has a raised temperature but not verified by thermometer.

To assess the safety and tolerability of a single dose of NmCV-5 or MenACWY-TT, when given concomitantly with routine vaccines, all unsolicited AEs occurring through 28 days after meningococcal vaccination are reported. Unsolicited AEs include AEs reported in scheduled or interim (unscheduled) visits after receipt of meningitis vaccination and with date of onset up to and including Study Day 29. Endpoints are the number of participants reporting at least one unsolicited adverse event (overall and by MedDRA preferred term).

Null hypothesis: The immune response to meningitis serogroup X at Day 29 elicited by one dose of NmCV-5 is not superior to the immune response elicited by one dose of MenACWY-TT, Alternative hypothesis: The immune response to meningitis serogroup X at Day 29 elicited by one dose of NmCV-5 is superior, by a pre-specified margin, to the immune response elicited by one dose of MenACWY-TT. Endpoints are the seroprotective response to serogroup X in the NmCV-5 arm at Day 29 and the seroprotective response defined to serogroup X in the MenACWY-TT arm at Day 29 with seroprotective response defined as serogroup specific rSBA antibody titers ≥ 8. Superiority comparisons are made between study vaccination arms within each study age group (9 months or 15 months of age). Proportions and difference in proportions are reported as percentages (number of infants per 100).

Null hypothesis: The immune response to measles at Day 29 elicited by the MR vaccine when co-administered with one dose of NmCV-5 is inferior to the immune response elicited by the MR vaccine when co-administered with one dose of MenACWY-TT. Alternative hypothesis: The immune response to measles at Day 29 elicited by the MR vaccine when co-administered with one dose of NmCV-5 is non inferior, by a pre-specified margin, to the immune response elicited by the MR vaccine when co-administered with one dose of MenACWY-TT. Endpoints are the seropositive responses to measles vaccine at Day 29 post vaccination, defined as anti-measles IgG concentration \>200 mIU/mL. Non-inferiority comparisons are made between study vaccination arms within each study age group (9 months or 15 months of age). Proportions and difference in proportions are reported as percentages (number of infants per 100).

Null hypothesis: The immune response to rubella at Day 29 elicited by the MR vaccine when co-administered with one dose of NmCV-5 is inferior to the immune response elicited by the MR vaccine when co-administered with one dose of MenACWY-TT. Alternative hypothesis: The immune response to rubella at Day 29 elicited by the MR vaccine when co-administered with one dose of NmCV-5 is non inferior, by a pre-specified margin, to the immune response elicited by the MR vaccine when co-administered with one dose of MenACWY-TT. Endpoints are the seropositive responses to rubella vaccine at Day 29 post vaccination, defined as anti-rubella IgG concentration \>20 IU/mL. Non-inferiority comparisons are made between study vaccination arms within each study age group (9 months or 15 months of age). Proportions and difference in proportions are reported as percentages (number of infants per 100).

Null hypothesis: The immune response to yellow fever at Day 29 elicited by the yellow fever vaccine when co-administered with one dose of NmCV-5 is inferior to the immune response elicited by the yellow fever vaccine when co-administered with one dose of MenACWY-TT. Alternative hypothesis: The immune response to yellow fever at Day 29 elicited by the yellow fever vaccine when co-administered with one dose of NmCV-5 is non inferior, by a pre-specified margin, to the immune response elicited by the yellow fever vaccine when co-administered with one dose of MenACWY-TT. Endpoints are the seroprotective responses to yellow fever vaccine at Day 29 post vaccination, defined as yellow fever neutralizing antibody titers ≥10. Non-inferiority comparisons are made between study vaccination arms within the 9 months study age group only. Proportions and difference in proportions are reported as percentages (number of infants per 100).

For each study age group (9 months and 15 months) and for each of the five serogroups (A, C, W, Y, and X), geometric means and 95% CIs of rSBA titers at Day 29 are calculated by study vaccination arm within each study age group, and the Geometric Mean Titer (GMT) Ratio of rSBA titers at Day 29 for NmCV-5 relative to MenACWY-TT will be estimated, along with 95% CIs. The point and interval estimates will be obtained from a back transformation of the estimated difference in means of the log-transformed rSBA titers. Endpoints are the rSBA titer values for meningococcal serogroups A, C, W, Y and X, from samples collected at Visit 3 (Study Day 29).

To assess clinically significant immune response indicators elicited by a single dose of meningococcal vaccine, the number and proportion of participants with seroresponse in rSBA titers at Day 29 is calculated for meningococcal serogroups A, C, W, Y and X. Endpoints are the number and percentage of participants with seroresponse in rSBA titers to meningococcal serogroups A, C, W, Y and X, from samples collected at Visit 3 (Study Day 29), where seroresponse is defined as a post-immunization (Day 29) rSBA titer of 32 or greater if the participant's pre-immunization (Baseline) rSBA titer was \< 8; or a ≥ four-fold increase over baseline at Day 29 post-immunization if the participant's pre-immunization rSBA titer was ≥ 8. Seroresponse is calculated for each study vaccination arm within each study age group (9 months or 15 months of age). Proportions are reported as percentages (number of infants per 100).

To assess clinically significant immune response indicators elicited by a single dose of meningococcal vaccine, the Geometric Mean Fold Rise (GMFR) from baseline to Day 29 of rSBA titers to meningococcal serogroups A, C, W, Y and X is estimated, with 95% CI. Endpoints are the rSBA titer values for meningococcal serogroups A, C, W, Y and X from samples collected at Visit 1 (Day 1) and Visit 3 (Day 29). The point and interval estimates will be obtained from a back transformation of the estimated mean difference of the log-transformed rSBA titers.

To assess clinically significant immune response indicators elicited by a single dose of meningococcal vaccine, the number and proportion of participants with rSBA titers ≥ 128 at Day 29 is calculated for meningococcal serogroups A, C, W, Y and X. Endpoints are the number and proportion of participants with rSBA titers ≥ 128 for meningococcal serogroups A, C, W, Y and X, from samples collected at Visit 3 (Study Day 29). This is calculated for each study vaccination arm within each study age group (9 months or 15 months of age). Proportions are reported as percentages (number of infants per 100).