Evaluation of Immunogenicity and Safety of Pentavalent Meningococcal ABCYW Vaccine in Pediatric Populations Compared to Licensed Meningococcal Vaccines

The primary objective of this study is to describe the **safety profile** of the MenPenta vaccine formulations in healthy children, toddlers, and infants. Additionally, the study aims to evaluate the **immune response** to the MenPenta vaccine formulations and comparator vaccines at various stages: 30 days after the second dose of vaccination given at approximately 4 months of age, and 30 days after the third dose of vaccination given at 12-15 months of age, specifically in healthy infants. The immune response will be measured by hSBA in serogroups A, C, W-135, Y, and reference MenB strains. This is clinically relevant as it assesses the vaccine's ability to elicit a protective immune response, which is crucial for preventing meningococcal disease.

Secondary objectives include describing the immune response (breadth of coverage) in a panel of MenB strains 30 days after the last dose of vaccination against serogroup B when administered to healthy children, toddlers, and infants. This evaluation is important for understanding the vaccine's effectiveness across different age groups and its potential to provide broad protection against meningococcal serogroup B.

The clinical trial involves a total of **500 participants** who are being evaluated for the safety and immune response to the MenPenta vaccine formulations. The study population includes **healthy children** aged 2 to 9 years, toddlers aged 12 to 15 months, and infants aged 56 to 89 days. Both **male and female** subjects are included in the trial. Participants are required to be overtly healthy, as determined by medical evaluation, including medical history and physical examination. Infants and toddlers must be born at full term (≥37 weeks) with a birth weight ≥2.5 kg or after a gestation period above 28 weeks through 36 weeks with a birth weight ≥1.5 kg, and must be medically stable. The trial population was selected based on these criteria to ensure the inclusion of individuals who do not require significant medical support. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial also includes a vulnerable population, as indicated by the inclusion of infants and toddlers. The sponsor has not provided additional information regarding specific lifestyle factors or habits of the participants.

The clinical trial is designed as a **randomized**, **double-blind**, and controlled study to evaluate the **immunogenicity** and safety of investigational pentavalent meningococcal ABCYW vaccine formulations compared to licensed meningococcal vaccines. The trial will be conducted in three stages, targeting healthy children aged 2 to 9 years, toddlers aged 12 to 15 months, and infants aged 2 months. The primary objective is to assess the safety profile and immune response to the MenPenta vaccine formulations and comparator vaccines, with specific focus on the **hSBA** titers against meningococcal serogroups A, C, W-135, Y, and reference MenB strains.

The trial will span an estimated duration from January 2025 to December 2027. Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, health status, and medical stability. Following the initial screening, participants will receive the study interventions and attend follow-up visits to monitor for any adverse events and to collect blood samples for immunogenicity assessments. The end-of-study visit will conclude the participant's involvement, ensuring all safety and efficacy data are collected.

Participant involvement is expected to last up to 361 days, depending on the stage of the trial they are enrolled in. Conditions that may lead to early termination from the study include the occurrence of serious adverse events or any significant deviation from the protocol that compromises participant safety or data integrity. The trial will adhere to rigorous ethical standards and regulatory requirements to ensure the safety and well-being of all participants throughout the study duration.

The clinical trial involves the administration of several vaccines, each with specific characteristics and administration protocols. **MenQuadfi** is a solution for injection, specifically a **Meningococcal Group A, C, W, and Y conjugate vaccine**. It is administered via **intramuscular injection** with a dosage of 0.5 ml per dose. The maximum treatment period for this vaccine is 1 day, and it is produced by Sanofi Pasteur. The active substances include polysaccharides from Neisseria meningitidis serogroups A, C, W-135, and Y, each conjugated to tetanus toxoid carrier protein.

**Nimenrix** is a powder and solvent for solution for injection in a pre-filled syringe, also a **Meningococcal groups A, C, W-135, and Y conjugate vaccine**. It is administered intramuscularly with a dosage of 0.5 ml per dose, and the maximum total dose is 1.5 ml over a treatment period of 361 days. This vaccine is produced by Pfizer Europe MA EEIG and contains similar active substances as MenQuadfi, with the addition of a de-O-acetylated polysaccharide from Neisseria meningitidis group C.

**Bexsero** is a suspension for injection in a pre-filled syringe, a **Meningococcal group B vaccine** (rDNA, component, adsorbed). It is administered intramuscularly with a dosage of 0.5 ml per dose, and the maximum total dose is 1.5 ml over a treatment period of 361 days. Produced by GSK Vaccines S.R.L., it contains recombinant proteins from Neisseria meningitidis group B, produced in E. coli cells and adsorbed on aluminium hydroxide.

**Prevenar 13** is a suspension for injection, a **pneumococcal polysaccharide conjugate vaccine** (13-valent, adsorbed). It is administered intramuscularly with a dosage of 0.5 ml per dose, and the maximum total dose is 1.5 ml over a treatment period of 361 days. Produced by Pfizer Europe MA EEIG, it contains pneumococcal polysaccharides from 13 serotypes, each conjugated to CRM197 and adsorbed on aluminium phosphate.

**Hexyon** is a suspension for injection in a pre-filled syringe, a combination vaccine for **diphtheria, tetanus, pertussis (acellular, component), hepatitis B (rDNA), poliomyelitis (inactivated), and Haemophilus influenzae type b**. It is administered intramuscularly with a dosage of 0.5 ml per dose, and the maximum total dose is 1.5 ml over a treatment period of 361 days. Produced by Sanofi Pasteur Europe, it contains multiple antigens adsorbed on aluminium hydroxide.

**MenPenta fHD** and **MenPenta SD** are suspensions for injection, both serving as **pentavalent meningococcal vaccines**. They are administered intramuscularly with a dosage of 0.5 ml per dose, and the maximum total dose is 1 ml over a treatment period of 361 days. Produced by Sanofi Pasteur Inc., they contain polysaccharides from Neisseria meningitidis serogroups A, C, W-135, and Y, conjugated to tetanus toxoid, along with additional components RNMB1, RNMB2, NMBPBAS1, and RNMB3.

**RotaTeq** is an oral solution, a **rotavirus vaccine (live)**. It is administered orally with a dosage of 1.5 ml per dose, and the maximum total dose is 4.5 ml over a treatment period of 121 days. Produced by Merck Sharp & Dohme B.V., it contains live reassortants of human-bovine rotavirus serotypes G1, G2, G3, G4, and P1[8], produced on Vero cells.

The efficacy of the MenPenta vaccine formulations in the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the measurement of **hSBA** (human Serum Bactericidal Assay) antibody titers against meningococcal serogroups A, C, W, and Y, as well as the reference MenB strains. These titers will be evaluated pre-dose and 30 days after the second and third doses in infant participants. Additionally, the geometric mean titers (GMTs) of antibodies against these serogroups will be calculated, and the percentage of participants with hSBA titers equal to or greater than the lower limit of quantification (LLOQ) will be determined. The seroresponse to the vaccine will also be assessed in children and toddlers.

Secondary endpoints focus on the response to additional MenB strains, with similar measurements of hSBA titers and GMTs in children, toddlers, and infants. The percentage of participants with antibody titers against these additional strains will be evaluated at thresholds of ≥1:4 and ≥1:8. The efficacy assessments will be conducted at specified time points, including pre-dose and one month after the second and third doses, to capture the immune response over time. These assessments will provide comprehensive data on the immunogenicity of the MenPenta vaccine formulations compared to licensed meningococcal vaccines.