Evaluation of Immune Response and Safety of rMenB+OMV NZ Vaccine in Adolescents and Young Adults Previously Primed for Invasive Meningococcal Disease

The primary objective of this study is to demonstrate the superiority of the **immune response** to one booster dose of the meningococcal group B vaccine, rMenB+OMV NZ, in participants who were primed during the first two years of life, compared to the response to the first dose in a naïve group. This is clinically relevant as it aims to establish the enhanced efficacy of the booster dose in providing protection against invasive meningococcal disease (IMD), a serious and potentially life-threatening condition.

Secondary objectives include:

• Evaluating the humoral immune response to one booster dose of rMenB+OMV NZ in the primed group and the first dose in the naïve group.
• Assessing the bactericidal activity at baseline in both the primed and naïve groups.
• Evaluating the safety of rMenB+OMV NZ throughout the study period.

The clinical trial involves a total of **65 participants** who are being studied in relation to **invasive meningococcal disease (IMD)**. The study population includes both male and female subjects, aged between **10 and 20 years**. Participants were selected based on their vaccination history, with two distinct groups: a primed group, who received the rMenB + OMV NZ vaccine in a 3+1 or 2+1 schedule during their first two years of life, and a naïve group, who have never received any group B meningococcal vaccine. The trial includes individuals who are capable of complying with the study requirements, as assessed by the investigator. Participants' general health status is not specified, but the study does consider lifestyle factors such as contraception use for female participants of childbearing potential. The trial population is inclusive of vulnerable groups, and both genders are represented. The selection criteria ensure that participants are able to provide informed consent or assent, as appropriate for their age and legal requirements.

The clinical trial is designed to evaluate the **immune response** and safety of the meningococcal group B vaccine, rMenB+OMV NZ, in healthy participants aged 10 to 20 years who were primed during the first two years of life. This is a Phase 3b, open-label, multi-center study. The trial aims to demonstrate the superiority of the immune response to one booster dose of rMenB+OMV NZ in the primed group compared to the first dose in a naïve group against each MenB indicator strain. The study is expected to commence on August 20, 2025, and conclude by December 9, 2025.

The trial follows a structured sequence of study visits. The inclusion visit, or screening visit, is conducted to confirm eligibility based on the inclusion criteria, which include prior vaccination records and the ability to comply with the study protocol. Participants are then administered the vaccine via **intramuscular injection**. Follow-up visits are scheduled to monitor the **hSBA titers** against each MenB indicator strain, with primary endpoints assessed at Visit 2 (Day 31). Secondary endpoints include the occurrence of solicited administration site and systemic events within seven days following the first vaccination, and any unsolicited adverse events (AEs) within 31 days, including serious adverse events (SAEs) and adverse events of special interest (AESI) such as arthritis. The end-of-study visit marks the completion of the participant's involvement in the trial.

Participant involvement is expected to last approximately 31 days, from the initial vaccination to the final follow-up visit. Conditions that may lead to early termination from the study include the occurrence of severe adverse events or the participant's inability to comply with the study protocol. The trial is conducted under strict adherence to ethical guidelines, with informed consent obtained from participants or their legally acceptable representatives prior to any study-specific procedures. The study is not categorized as low intervention and is classified as a Phase IIIa clinical trial.

The clinical trial involves the administration of **Bexsero**, a suspension for injection in a pre-filled syringe, which is a **Meningococcal group B Vaccine** (rDNA, component, adsorbed). The vaccine is designed to protect against infections caused by **Neisseria meningitidis** group B. The active substances in Bexsero include recombinant proteins produced in **E. coli** cells by recombinant DNA technology, specifically the NHBA fusion protein, NadA protein, and fHbp fusion protein, all adsorbed on **aluminium hydroxide**. Additionally, the vaccine contains outer membrane vesicles (OMV) from Neisseria meningitidis group B strain NZ98/254, measured as the amount of total protein containing the PorA P1.4, also adsorbed on aluminium hydroxide. The pharmaceutical form is a suspension for injection, and the vaccine is administered via **intramuscular injection**.

The dosage for Bexsero is 0.5 ml per administration, with a maximum total dose of 1 ml. The treatment period is limited to a maximum of 1 day. The vaccine is provided in a pre-filled syringe made of type 1 glass, equipped with a plunger stopper made of butyl rubber and a rubber tip cap. The administration schedule and participant compliance are monitored throughout the trial to ensure adherence to the dosing regimen. The trial does not include any non-experimental treatments such as a placebo or comparator treatment, as the focus is on assessing the immune response and safety of the Bexsero vaccine in the specified population.

The efficacy of the meningococcal group B vaccine, Bexsero, will be assessed in a Phase 3b, open-label, multi-center clinical trial. The primary endpoint for evaluating efficacy is the measurement of **hSBA titers** against each MenB indicator strain at Visit 2, which occurs on Day 31. Secondary endpoints include the assessment of hSBA titers at both Visit 1 (Day 1) and Visit 2 (Day 31), as well as the occurrence of solicited administration site and systemic events within 7 days following the first vaccination. Additionally, the trial will monitor the occurrence of any unsolicited adverse events (AEs) within 31 days, including the day of injection, and the occurrence of adverse events of special interest (AESI), serious adverse events (SAEs), and AEs leading to withdrawal throughout the study period from Day 1 to Day 31.