A Phase 3 Trial to Evaluate the Safety, Immunogenicity, and Non-Interference With Concomitant Routine Vaccines, of a Meningococcal Serogroup ACYWX Conjugate Vaccine (NmCV-5) in Comparison With MenACWY-TT Conjugate Vaccine in Healthy Malian Infants

Meningococcal meningitis, caused by invasive strains of Neisseria meningitidis, is a major public health concern because of its considerable morbidity and mortality in sub-Saharan Africa. Case fatality during meningococcal meningitis epidemics can surpass 15%, and rates of permanent sequelae among meningitis survivors in Africa are twice as high as they are in high income countries. Because of the fulminant clinical course of invasive bacterial meningitis and difficulties in access to care in the African meningitis belt, prevention by vaccination is the optimal way to reduce meningococcal meningitis morbidity and mortality. Before 2010, serogroup A meningococcal strains were routinely responsible for the majority (70-96%) of invasive meningococcal disease in sub-Saharan Africa. And annual epidemic could be associated with an incidence of meningococcal disease which could range between 100-1000 cases per 100,000 persons in any given year.

Progressive introduction of MenAfriVac since 2010 has resulted in a substantial reduction in cases of serogroup A meningococcal disease. However, regular large-scale epidemics due to serogroups C, W and X remain common in the African meningitis belt. An affordable and scalable pentavalent meningococcal conjugate vaccine (NmCV-5) has been developed by Serum Institute of India Pvt. Ltd. (SIIPL), the manufacturer of MenAfriVac. NmCV-5 is designed to protect against serogroups A, C, W, Y and X. The immediate goal for the clinical development of NmCV-5 is for WHO Pre-Qualification (WHO-PQ), to enable the vaccine to be used in the Meningitis Belt of sub-Saharan Africa.

This trial will evaluate a single dose of NmCV-5 administered at either 9 months or 15 months of age, time points in the Expanded Program on Immunization (EPI) schedule when meningococcal vaccine is most likely to be administered. Infants aged 9 months will be randomized to receive a meningococcal vaccine at 9 months or 15 months. Infants aged 9 months (eligibility 9-11 months) and randomized to the 9-month age group will be randomized in a 2:1 ratio to receive a single dose of NmCV-5 or a single dose of MenACWY-TT. Prospectively identified and consented infants randomized to the 15-month age group will return when aged 15 months (eligibility 15-17 months) and will be randomized in a 2:1 ratio to receive a single dose of NmCV-5 or a single dose of MenACWY-TT. "Enhanced" EPI vaccines will be co-administered and will consist of 2-doses of a measles-containing vaccine administered at 9 months and 15 months and a single dose of yellow fever vaccine administered at 9 months.

This study protocol is designed to provide evidence that concomitant vaccination with NmCV-5 will not significantly affect the immune responses of infants to their normally scheduled EPI vaccines. This study has been specifically designed to provide information at two distinct timepoints, 9 months and 15 months. The current Mali EPI schedule consists of a measles only vaccine, yellow fever vaccine, and MenA vaccine at 9 months of age; there is no 15 months of age EPI vaccine visit and typically only a single dose of a measles-containing vaccine is administered. However, to satisfy the conditions for WHO-PQ, study participants will receive two doses of a measles-containing vaccine, at 9-months and 15-months. Furthermore, the noninferiority evaluation must include an assessment of the rubella vaccine responses. These modifications to the standard Malian EPI schedule provide a level-of-care that is higher than the current standard-of-care for the general population. Within the context of this study, the researchers will refer to this as an "enhanced" EPI schedule.