Safety Evaluation of GSKVX000000025896 Versus Varicella Virus Oka/Merck Strain in Healthy Children Aged 12-15 Months

The primary objective of this Phase 3a, observer-blind, randomized, controlled study is to evaluate the **safety** and reactogenicity of an investigational varicella vaccine (VNS) compared to Varivax, when co-administered with the measles, mumps, and rubella (MMR) vaccine, hepatitis A (HAV) vaccine, and, if applicable, the pneumococcal conjugate vaccine (PCV) in healthy children aged 12 to 15 months. This evaluation is clinically relevant as it aims to ensure the safety profile of the investigational vaccine in comparison to an established vaccine, Varivax, thereby potentially offering an alternative option for varicella immunization in pediatric populations.

The clinical trial involves a total of **414 participants** who are being evaluated for the safety and reactogenicity of the VNS vaccine and VV when co-administered with the MMR vaccine, HAV vaccine, and, if applicable, PCV. The study population consists of healthy male and female children aged between 12 to 15 months. Participants were selected based on their health status, as established by medical history and clinical examination, ensuring they are healthy before entering the study. The trial includes children from countries where PCV is recommended at 12 to 15 months of age, provided they have previously received the primary series of PCV in the first year of life, with the last dose administered at least 60 days prior to study entry. The trial population is considered a **vulnerable population** due to the young age of the participants. The selection process also required informed consent from the participants' parents or legally authorized representatives, who must comply with the study protocol requirements.

The clinical trial is designed as a **randomized**, observer-blind, controlled study to evaluate the safety of an investigational varicella vaccine compared to Varivax, administered as a first dose to healthy children aged 12 to 15 months. The trial aims to assess the safety and reactogenicity of the investigational vaccine when co-administered with the MMR vaccine, HAV vaccine, and, if applicable, PCV. The study is expected to commence on June 12, 2025, and conclude by December 5, 2025, with an overall duration of approximately six months for each participant.

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 previous vaccination history. Following the initial administration of the study interventions, participants will be monitored for solicited administration site events within four days, systemic events within 15 days, and specific systemic events such as fever within 22 days. Additionally, administration site and systemic events, including rash, will be observed within 43 days post-dose. Unsolicited adverse events (AEs) will be recorded within 43 days, and any medically attended AEs and serious adverse events (SAEs) will be monitored up to the study's end on Day 181.

The expected length of participant involvement is approximately six months, with conditions for early termination including the occurrence of significant adverse events or non-compliance with study protocols. The trial will ensure that all procedures adhere to ethical standards, with informed consent obtained from the participant's parent(s) or legally authorized representative(s) prior to any study-specific procedures. The study will maintain a high standard of scientific rigor, ensuring the reliability and validity of the findings related to the safety profile of the investigational varicella vaccine.

The clinical trial involves the administration of an **experimental varicella vaccine** developed by GlaxoSmithKline Biologicals S.A. This investigational product is formulated as a **suspension for injection** and is administered subcutaneously. The dosage for this vaccine is 0.5 ml per administration, with a maximum treatment period of one day. The vaccine is a structurally diverse substance classified as a biological product. The administration involves a drug product diluent in a prefilled syringe co-packed with a lyophilized drug product vial. Participant compliance is monitored through standard clinical trial procedures.

The comparator treatment in this study is **VARIVAX®**, a varicella vaccine produced by MSD Sharp & Dohme GmbH. This vaccine is also a **suspension for injection** and is administered subcutaneously. The active substance in VARIVAX® is the **varicella virus Oka/Merck strain (live, attenuated)**, produced in human diploid (MRC-5) cells. The dosage is identical to the experimental vaccine, with 0.5 ml administered per dose, and the treatment period is limited to one day. VARIVAX® is a well-established vaccine used as a standard-of-care therapy in this trial.

Both vaccines are administered as a first dose to healthy children aged 12 to 15 months. The trial aims to evaluate the safety and reactogenicity of the investigational vaccine compared to VARIVAX® when co-administered with other vaccines such as the MMR vaccine, HAV vaccine, and, if applicable, PCV. The study is conducted under observer-blind conditions to ensure unbiased assessment of outcomes.

Efficacy in this clinical trial will be assessed through the evaluation of primary endpoints related to the occurrence of specific events following the administration of the investigational varicella vaccine and the comparator, Varivax. The primary endpoints include the occurrence of solicited administration site events within 4 days post-dose, systemic events within 15 days post-dose, systemic fever events within 22 days post-dose, and administration site and systemic rash events within 43 days post-dose. Additionally, the occurrence of any unsolicited adverse events (AEs) within 43 days post-dose, any medically attended AEs up to the study end (Day 181), and serious adverse events (SAEs) up to the study end will be monitored.

The efficacy parameters will be collected and analyzed at specified timepoints, including Day 1 to Day 4, Day 1 to Day 15, Day 1 to Day 22, and Day 1 to Day 43, with follow-up extending to Day 181 for certain endpoints. The study will utilize validated scales and methods to ensure accurate and reliable data collection. The investigational product is administered subcutaneously as a suspension for injection, and the trial is designed to be observer-blind and randomized, ensuring objective assessment of the vaccine's efficacy.