Evaluation of Safety, Tolerability, and Immunogenicity of MenABCWY-2nd Gen Vaccine in Healthy Infants with Meningococcal Infections

The primary objective of this Phase II, randomized, partially blinded study is to evaluate the **safety** and **reactogenicity** of two formulations of the MenABCWY-2nd Gen vaccine, the MenABCWY-1st Gen, the MenB vaccine, and the MenACWY-TT vaccine in healthy infants. This is clinically relevant as it aims to ensure that these vaccines are safe for administration in a vulnerable population, thereby potentially reducing the incidence of meningococcal infections. Additionally, the study seeks to assess the **immune response** to the two formulations of the MenABCWY-2nd Gen vaccine, the MenABCWY-1st Gen, and the MenB vaccine against all serogroup B indicator strains. Furthermore, it evaluates the immune response to the two formulations of the MenABCWY-2nd Gen vaccine, the MenABCWY-1st Gen vaccine, and the MenACWY-TT vaccine against serogroups A, C, W, and Y. This is crucial for determining the vaccines' efficacy in eliciting a protective immune response, which is essential for preventing meningococcal disease in infants.

The clinical trial involves a total of **206 participants** who are healthy infants, both male and female, aged between 55 and 89 days. These participants were selected based on specific criteria, including being born after a gestation period of at least 37 weeks and having a birth weight of at least 2.5 kg. The study population is characterized by their general good health, as determined by medical history and clinical examination prior to enrollment. The trial focuses on evaluating the safety, reactogenicity, and immune response of various formulations of the MenABCWY vaccine against **meningococcal infections**. Participants' parents or legally acceptable representatives provided informed consent, ensuring compliance with the study protocol. The trial does not specify any particular lifestyle considerations such as diet or physical activity for the participants, given their young age. The inclusion of a vulnerable population is noted, reflecting the careful consideration of ethical standards in the study design.

The clinical trial is designed as a **randomized**, partially blinded study to evaluate the safety, tolerability, and immunogenicity of a meningococcal combined ABCWY vaccine when administered to healthy infants. The trial will involve multiple study visits over an estimated duration from December 2021 to March 2025. Participants will be randomly assigned to receive one of the vaccine formulations, ensuring a controlled comparison of outcomes. The study will include a series of visits, starting with an inclusion (screening) visit to confirm eligibility based on criteria such as age, health status, and birth conditions. This visit will involve obtaining informed consent from the participants' parents or legally acceptable representatives.

Following the screening, participants will attend scheduled vaccination visits where they will receive the assigned vaccine formulation via **intramuscular use**. The primary endpoints will assess the number and percentage of participants experiencing solicited administration site and systemic events within seven days post-vaccination, as well as any unsolicited adverse events over 30 days. The immune response will be evaluated through human serum bactericidal assay (hSBA) titres at specified intervals, including one month after the second vaccination and pre- and post-third vaccination. Follow-up visits will monitor for medically attended adverse events, serious adverse events, and adverse events of special interest throughout the study duration.

The expected length of participant involvement is approximately 15 months, with conditions for early termination including the occurrence of serious adverse events or withdrawal of consent. The end-of-study visit will conclude the trial, ensuring all data is collected and participants' health is assessed. The trial's design and procedures are structured to maintain scientific rigor and participant safety, adhering to ethical standards and regulatory requirements.

The clinical trial involves the administration of several experimental and non-experimental treatments. The primary experimental treatment is the **MenABCWY** vaccine, which is a **suspension for injection**. This vaccine contains multiple active substances, including **Meningococcal Group Y Oligosaccharide Conjugated to Corynebacterium diphtheriae CRM197 Protein**, **N. meningitidis Group C (Strain C11) Polysaccharide Conjugated CRM197**, **N. meningitidis Group A Oligosaccharide Conjugated CRM197**, **N. meningitidis Group W135 Oligosaccharide Conjugated CRM197**, and several recombinant proteins produced in E. coli cells by recombinant DNA technology, all adsorbed on aluminium hydroxide. The vaccine is administered via **intramuscular use**. The dosing schedule and frequency of administration are determined by the study protocol, and participant compliance is monitored throughout the trial.

Another experimental treatment in the study is the **NM401C/NMB10A** vaccine, also a **suspension for injection**. This formulation includes similar active substances as the MenABCWY vaccine, with the addition of a unique component identified as **GSKVX000000017986**. The administration route is **intramuscular**, and the dosing schedule is aligned with the study's objectives to evaluate safety and immunogenicity.

The study also includes the **NM401C/NMB10B** vaccine, which is a **suspension for injection**. This vaccine shares the same active substances as the NM401C/NMB10A formulation, including the unique component **GSKVX000000017986**. It is administered intramuscularly, and the dosing schedule is consistent with the trial's design to assess the immune response and safety profile.

As a comparator treatment, the study utilizes the **Nimenrix** vaccine, a **powder and solvent for solution for injection** in a pre-filled syringe. This vaccine targets **Meningococcal groups A, C, W-135, and Y**, with each polysaccharide conjugated to tetanus toxoid carrier protein. The administration is via **intramuscular use**, and it serves as a benchmark to evaluate the experimental vaccines' efficacy and safety.

Additional non-experimental treatments include the **Infanrix hexa** vaccine, a **powder and suspension for suspension for injection**. This vaccine is a combination of diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and Haemophilus influenzae type b conjugate vaccine. It is administered intramuscularly and is used to provide standard immunization coverage in the study population.

The study also incorporates the **Rotarix** vaccine, an **oral suspension** in a pre-filled oral applicator. This live attenuated rotavirus vaccine is administered orally and is included to ensure comprehensive immunization against rotavirus in the study cohort.

Lastly, the **Bexsero** vaccine, a **suspension for injection** in a pre-filled syringe, is used as a comparator. It targets **Meningococcal group B** and includes recombinant proteins produced in E. coli cells by recombinant DNA technology, adsorbed on aluminium hydroxide. The administration is intramuscular, and it serves to compare the immunogenicity and safety of the experimental vaccines against a licensed meningococcal B vaccine.

Participant compliance with the dosing schedule is monitored through regular follow-ups and documentation, ensuring adherence to the study protocol. The trial's design aims to evaluate the safety, tolerability, and immunogenicity of the experimental vaccines compared to standard and licensed vaccines.

The efficacy of the MenABCWY vaccine in the clinical trial will be assessed through several primary endpoints. These include the measurement of human serum bactericidal assay (**hSBA**) titres, which will be evaluated for each serogroup A, C, W, and Y, as well as for each serogroup B indicator strain. The hSBA titres will be measured at specific timepoints: one month after the second vaccination (Day 91), pre-third vaccination (Day 301), and one month after the third vaccination (Day 331). Additionally, the hSBA geometric mean titres (GMTs) and geometric mean ratios (GMRs) will be calculated for these serogroups and strains at Day 331 compared to pre-third vaccination levels.

The collection and analysis of these efficacy parameters will be conducted using validated laboratory tests to ensure accuracy and reliability. The schedule for these assessments is strategically planned to capture the immune response at critical intervals following vaccination. This approach allows for a comprehensive evaluation of the vaccine's ability to elicit an immune response against the targeted meningococcal serogroups, thereby providing insights into its potential efficacy in preventing infections caused by these pathogens.