Evaluation of Immunogenicity and Safety of MenACYW Conjugate Vaccine Booster in Pediatric and Adolescent Populations with Prior Vaccination

The primary objective of this study is to evaluate the **immunogenicity** and safety of a booster dose of the MenACYW conjugate vaccine in children and adolescents who were previously vaccinated as toddlers. This evaluation is crucial for understanding the long-term effectiveness and safety profile of the vaccine, which targets **meningococcal infection** caused by serogroups A, C, W, and Y. Additionally, the study aims to describe the immune persistence of the priming dose and the first booster dose in adolescents, providing insights into the duration of protection offered by the vaccine.

Secondary objectives include:

• Describing antibody persistence and responses to meningococcal serogroups A, C, W, and Y in children and adolescents who received the MenACYW conjugate vaccine 5 or 10 years earlier, as well as in those who received a booster dose 5 years after the primary dose.
• Describing antibody responses to **tetanus toxoid** before and 30 days after each booster dose of the MenACYW vaccine in the same population.
• Describing antibody responses to meningococcal serogroup C before and 30 days after a booster dose in children and adolescents who were either meningococcal vaccine-naïve or MenC-primed as toddlers, and in adolescents who received a booster dose 5 years after the primary dose.

The clinical trial involves a study population of children and adolescents who previously participated in the MET51 study and received the **MenACYW conjugate vaccine**. The trial includes both male and female participants, with an age range corresponding to those who were vaccinated approximately 5 or 10 years earlier as toddlers. The study population is drawn from Finland, Germany, Spain, and Hungary. Participants are required to have completed the MET51 study and attended all necessary visits. The trial population includes individuals who are covered by health insurance, if mandated by local regulations, and who have provided the necessary assent and informed consent. The sponsor has not provided the total number of participants. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The study includes a vulnerable population, indicating that special considerations are in place to ensure the safety and ethical treatment of participants.

The clinical trial is designed to evaluate the **immunogenicity** and safety of a booster dose of the MenACYW conjugate vaccine in children and adolescents who were previously vaccinated as toddlers. This Phase IIIb, open-label, multi-center study will assess the immune persistence of the vaccine and the seroresponse sufficiency against **meningococcal infection** serogroups A, C, W, and Y. The trial will follow a non-randomized, controlled design, with participants receiving the vaccine via **intramuscular injection**. The study is expected to span from August 2022 to April 2028, with participant involvement lasting up to 62 days.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as previous participation in the MET51 study and the ability to comply with trial procedures. Following the screening, participants will attend multiple follow-up visits to monitor antibody titers and assess any adverse events. The primary endpoint is the vaccine seroresponse against the specified meningococcal serogroups, while secondary endpoints include antibody titers and concentrations at various visits, as well as the incidence of adverse events.

The end-of-study visit will conclude the participant's involvement, during which final assessments of immunogenicity and safety will be conducted. Participants may be terminated early from the study if they fail to meet ongoing eligibility criteria, experience significant adverse events, or are unable to comply with the study protocol. The trial aims to provide comprehensive data on the long-term efficacy and safety of the MenACYW conjugate vaccine in a pediatric and adolescent population.

The clinical trial involves the administration of **MenQuadfi**, a **Meningococcal Group A, C, W, and Y conjugate vaccine**. This experimental medication is provided in the form of a **solution for injection**. The active substances in MenQuadfi include **tetanus toxoid** and polysaccharides from **Neisseria meningitidis** groups A, C, W-135, and Y, each conjugated to a tetanus toxoid carrier protein. The vaccine is administered via **intramuscular injection**. The dosage for this trial is set at a maximum of 0.5 ml per day, with a total maximum dose of 1 ml over the treatment period. The treatment period is defined as 62 days. The vaccine is not a pediatric formulation and is not classified as an orphan drug.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the immunogenicity and safety of the MenQuadfi vaccine. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol. The trial aims to assess the immune response and safety profile of the vaccine in children and adolescents who have previously received the MenACYW conjugate vaccine.

The efficacy of the MenACYW conjugate vaccine in the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint focuses on the **vaccine seroresponse** against meningococcal serogroups A, C, W, and Y. This will be evaluated to determine the sufficiency of the immune response following the administration of a booster dose in children who received the initial dose approximately five years earlier.

Secondary endpoints include measuring antibody titers against meningococcal serogroups A, C, W, and Y at various visits, specifically before and after the booster dose administration. These measurements will be taken at multiple timepoints, including Visit 1, Visit 2, Visit 3, and Visit 4, to assess the persistence of the immune response over time. Additionally, antibody concentrations against **tetanus toxoid** will be evaluated at specified visits to further understand the immunogenicity profile of the vaccine.

The collection and analysis of these efficacy parameters will involve laboratory tests to quantify antibody titers and concentrations. The trial will also monitor the number of participants experiencing immediate unsolicited systemic adverse events, solicited injection site reactions, systemic reactions, unsolicited adverse events, serious adverse events, and adverse events of special interest. These assessments will provide comprehensive data on both the immunogenicity and safety of the MenACYW conjugate vaccine in the study population.