Evaluation of Safety and Immunogenicity of V116 in Pediatric Patients at Increased Risk for Pneumococcal Disease: A Phase 3 Randomized, Double-Blind Study

The primary objective of this Phase 3, randomized, double-blind study is to evaluate the **safety** and tolerability of the V116 vaccine in children and adolescents with increased risk of **pneumococcal disease**. This is assessed by determining the proportion of participants experiencing adverse events (AEs). Additionally, the study aims to compare the serotype-specific opsonophagocytic (OPA) geometric mean titers (GMTs) at 30 days post-vaccination with V116 versus PPSV23. These objectives are clinically relevant as they provide critical insights into the vaccine's safety profile and its immunogenic efficacy, which are essential for its potential use in a vulnerable population.

Secondary objectives include: - Evaluating the serotype-specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) at 30 days post-vaccination with V116 compared to PPSV23. - Assessing the serotype-specific geometric mean fold rises (GMFRs) and the proportions of participants with a ≥4-fold rise in serotype-specific OPA responses and IgG responses from baseline to 30 days post-vaccination within each vaccination group. These secondary objectives further elucidate the immunogenic response elicited by the vaccine, contributing to a comprehensive understanding of its efficacy.

The clinical trial involves a total of **605 participants** who are being evaluated for the safety and tolerability of a vaccine related to **pneumococcal disease**. The study population includes both male and female subjects, with an age range that is not specified in the provided data. Participants were selected based on specific risk conditions for pneumococcal disease, such as diabetes mellitus, chronic liver, lung, heart, or kidney disease, and must be receiving stable medical management for these conditions for at least three months. Additionally, participants should not have received more than one dose of the pneumococcal vaccine (PPSV23) within five years prior to the study vaccination. The trial includes a vulnerable population, although specific lifestyle considerations such as diet or physical activity are not detailed in the available information.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the safety, tolerability, and immunogenicity of the investigational vaccine V116 in children and adolescents with increased risk of **pneumococcal disease**. The trial will compare V116 with the comparator vaccine, Pneumovax® 23, in terms of serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) at 30 days post-vaccination. The study is expected to commence on January 10, 2024, and conclude by February 12, 2025, with an overall duration of approximately 13 months.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific risk conditions such as diabetes mellitus, chronic liver, lung, heart, or kidney disease. Eligible participants must have been receiving stable medical management for at least three months and should not have received more than one dose of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) within five years prior to the study. The inclusion visit will be followed by the administration of the investigational or comparator vaccine.

Subsequent follow-up visits will be scheduled to monitor the occurrence of adverse events (AEs), including solicited injection-site and systemic AEs, as well as vaccine-related serious adverse events (SAEs). The primary endpoints include the percentage of participants experiencing these AEs and the measurement of serotype-specific OPA GMTs. Secondary endpoints will assess geometric mean concentrations (GMCs) of serotype-specific Immunoglobulin G (IgG) and the geometric mean fold rise (GMFR) from baseline in serotype-specific OPA GMTs and IgG GMCs.

The end-of-study visit will conclude the participant's involvement, which is anticipated to last for the duration of the trial. Conditions that may lead to early termination from the study include the occurrence of significant adverse events or non-compliance with study procedures. The trial aims to provide comprehensive data on the safety and immunogenicity of V116, contributing to the understanding of its potential use in populations at increased risk for pneumococcal disease.

The clinical trial involves the administration of three different **vaccines**. The first experimental medication is **Pneumovax® 23**, a pneumococcal polysaccharide vaccine. It is provided as a solution for injection in a pre-filled syringe. The active substances include a range of pneumococcal polysaccharide serotypes, specifically serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F. The vaccine is administered intramuscularly at a dosage of 0.5 ml. The maximum treatment period is one day, with a single dose administered.

The second experimental medication is **V110**, also a pneumococcal polysaccharide vaccine, provided as a solution for injection. It contains the same active substances as Pneumovax® 23, covering the same serotypes. The administration route is intramuscular, with a dosage of 0.5 ml. The treatment period is limited to one day, with a single dose given.

The third experimental medication is the **Pneumococcal 21-valent Conjugate Vaccine**, known as V116. This vaccine is also a solution for injection and includes pneumococcal polysaccharide serotypes conjugated to CRM197, such as serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15B, 17F, 19A, 20, 22F, and 33F, along with additional conjugated serotypes ABC-15BO-116, ABC-15A-116, ABC-16F-116, ABC-23A-116, ABC-24F-116, ABC-23B-116, ABC-31-116, and ABC-35B-116. The vaccine is administered intramuscularly at a dosage of 0.5 ml, with a maximum treatment period of one day, involving a single dose.

All vaccines are classified as biological products and are not paediatric formulations. Participant compliance is monitored through standard clinical trial procedures, ensuring adherence to the dosing schedule. The trial aims to evaluate the safety, tolerability, and immunogenicity of these vaccines in children and adolescents at increased risk of pneumococcal disease.

The efficacy of the clinical trial will be assessed through several primary and secondary endpoints. The primary endpoints include the evaluation of the **geometric mean titers (GMTs)** of serotype-specific opsonophagocytic activity (OPA) following vaccination. This will be compared at 30 days post-vaccination with V116 versus PPSV23. Additionally, the percentage of participants with solicited injection-site adverse events (AEs), solicited systemic AEs, and vaccine-related serious adverse events (SAEs) will be monitored.

Secondary endpoints will focus on the **geometric mean concentrations (GMCs)** of serotype-specific Immunoglobulin G (IgG) after vaccination, as well as the geometric mean fold rise (GMFR) from baseline in serotype-specific OPA GMTs. The trial will also measure the percentage of participants with a ≥4-fold rise from baseline in serotype-specific OPAs GMTs and IgG GMCs. These parameters will be collected and analyzed to determine the immunogenicity and overall efficacy of the vaccine in children and adolescents with increased risk of pneumococcal disease.