Phase III Study on Immunogenicity and Safety of MenACYW Conjugate Vaccine Versus Nimenrix in Healthy Infants and Toddlers

The primary objective of this study is to demonstrate the non-inferiority of the antibody response, measured in terms of geometric mean titers (GMTs), against meningococcal serogroups A, C, W, and Y. This evaluation follows the administration of a 2-dose series (1+1) of the MenACYW conjugate vaccine compared to a 2-dose series (1+1) of Nimenrix®, with each vaccine administered to infants at 6-7 months of age and toddlers at 12-13 months of age. The clinical relevance of this objective lies in ensuring that the MenACYW vaccine provides an immune response that is at least as effective as the established Nimenrix® vaccine, which is crucial for the prevention of meningococcal infections in this vulnerable population. Secondary objectives include: - Comparing seroprotection against meningococcal serogroups ACWY, 30 days after administration of the priming dose of MenACYW conjugate vaccine versus the priming dose of Nimenrix® in infants aged 6-7 months. - Describing the antibody response against meningococcal serogroups ACWY before vaccination and 30 days after administration of the priming dose of either MenACYW vaccine or Nimenrix® in infants aged 6-7 months. - Describing the antibody response against meningococcal serogroups ACWY before and 30 days after administration of the booster dose of either MenACYW vaccine or Nimenrix® in toddlers aged 12-13 months. - Describing the antibody response against meningococcal serogroups ACWY before the priming dose in infants aged 6-7 months and 30 days following administration of the booster dose of either MenACYW vaccine or Nimenrix® in toddlers aged 12-13 months. - Describing the safety profile of the MenACYW vaccine and Nimenrix® after the priming dose administered to infants at 6-7 months old and after the booster dose administered at 12-13 months old.

The clinical trial involves healthy volunteers with a focus on meningococcal infection. The study population consists of infants aged 6 to 7 months and toddlers aged 12 to 13 months, encompassing both male and female participants. The participants are required to be in good health, as determined by a comprehensive medical evaluation, including medical history and physical examination. The trial population was selected based on specific age criteria and health status, ensuring that only those deemed healthy by the investigator's judgment were included. The sponsor has not provided information regarding the total number of participants. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, given the young age of the participants.

The clinical trial is designed to evaluate the immunogenicity and safety of a quadrivalent meningococcal conjugate vaccine compared to Nimenrix® in healthy infants and toddlers. This is a Phase III, modified double-blind, randomized, controlled study with two parallel groups. The trial aims to demonstrate the non-inferiority of the antibody response in terms of geometric mean titers (GMTs) against meningococcal serogroups A, C, W, and Y. The study will involve administering a 2-dose series (1+1) of the MenACYW conjugate vaccine and Nimenrix® to participants at 6-7 months and 12-13 months of age. The trial is expected to commence recruitment on February 19, 2024, and conclude by August 12, 2025. Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (6 to 7 months) and health status. The primary endpoint is the measurement of GMTs of antibodies against the specified meningococcal serogroups. Secondary endpoints include hSBA and rSBA antibody titers, seroresponse rates, and the incidence of adverse events. Follow-up visits will be scheduled to monitor the participants' response to the vaccine and any adverse events. The end-of-study visit will assess the overall safety and immunogenicity outcomes. The expected duration of participant involvement is approximately 7 months, covering the period from the first dose at 6-7 months of age to the final follow-up after the second dose at 12-13 months. Conditions that may lead to early termination from the study include the occurrence of serious adverse events or withdrawal of consent by the participant's guardian. The study will adhere to rigorous ethical standards and regulatory requirements to ensure the safety and well-being of all participants.

The clinical trial involves the administration of two vaccines: MenQuadfi and Nimenrix. MenQuadfi is a quadrivalent meningococcal conjugate vaccine, formulated as a solution for injection. It contains polysaccharides from Neisseria meningitidis serogroups A, C, W, and Y, each conjugated to tetanus toxoid. The vaccine is manufactured by Sanofi Pasteur and is administered via intramuscular injection. The dosage is 0.5 ml per administration, with a maximum total dose of 1 ml over the treatment period. The vaccine is given in a 1+1 schedule, with the first dose administered to infants at 6-7 months of age and the second dose to toddlers at 12-13 months of age. The maximum treatment period is 7 days. Nimenrix is also a quadrivalent meningococcal conjugate vaccine, provided as a powder and solvent for solution for injection in a pre-filled syringe. It contains polysaccharides from Neisseria meningitidis groups A, C, W-135, and Y, each conjugated to tetanus toxoid. This vaccine is produced by Pfizer Europe MA EEIG and is administered via intramuscular injection. The dosage is 0.5 ml per administration, with a maximum total dose of 1 ml over the treatment period. Similar to MenQuadfi, Nimenrix is administered in a 1+1 schedule, with the first dose given to infants at 6-7 months of age and the second dose to toddlers at 12-13 months of age. The maximum treatment period is 7 days. Both vaccines are used in the study to compare their immunogenicity and safety profiles. The primary objective is to demonstrate the non-inferiority of the antibody response, measured by geometric mean titers (GMTs), against meningococcal serogroups A, C, W, and Y. The study is designed as a parallel-group, prevention, Phase III, modified double-blind, 2-arm trial. Participant compliance with the dosing schedule is monitored throughout the study to ensure accurate assessment of the vaccines' efficacy and safety.

The efficacy of the quadrivalent meningococcal conjugate vaccine (MenACYW conjugate vaccine) will be assessed in a Phase III clinical trial by evaluating the geometric mean titers (GMTs) of antibodies against meningococcal serogroups A, C, W, and Y. The primary endpoint is to demonstrate non-inferiority of the antibody response in terms of GMTs following the administration of a 2-dose series (1+1) of MenACYW compared to a 2-dose series (1+1) of Nimenrix®. The vaccines will be administered to infants at 6-7 months of age and toddlers at 12-13 months of age. Secondary endpoints include the measurement of hSBA antibody titers against the same serogroups, with specific thresholds such as titers ≥ 1:8 and several pre-defined thresholds. The percentage of participants achieving a ≥4-fold rise in antibody titers over baseline, as measured by hSBA, will also be evaluated. Additionally, rSBA antibody titers and their response to the vaccine will be assessed. Safety endpoints will include the number of participants with immediate adverse events, solicited injection site reactions, systemic reactions, unsolicited adverse events, and serious adverse events. These parameters will be collected and analyzed to determine the immunogenicity and safety profile of the MenACYW conjugate vaccine compared to Nimenrix®.